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This open-label, multicenter, single-arm, phase 2 study assessed the safety and efficacy of blinatumomab consolidation therapy in adult patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL; International Prognostic Index 3-5 and/or double-/triple-hit or double MYC/BCL-2 expressors) who achieved complete response (CR), partial response (PR), or stable disease (SD) following run-in with 6 cycles of R-chemotherapy (NCT03023878). Of the 47 patients enrolled, 28 received blinatumomab. Five patients (17.9%) experienced grade 4 treatment-emergent adverse events of interest (neutropenia, n = 4; infection, n = 1). Two deaths reported at the end of the study were unrelated to treatment with blinatumomab (disease progression, n = 1; infection, n = 1). 3/4 patients with PR and 4/4 patients with SD after R-chemotherapy achieved CR following blinatumomab. Consolidation with blinatumomab in patients with newly diagnosed, high-risk DLBCL who did not progress under R-chemotherapy was better tolerated than in previous studies where blinatumomab was used for treatment of patients with lymphoma.

Most patients receiving CAR T-cell therapy (CAR-T) for aggressive B-cell lymphoma (B-NHL) will not experience a durable remission. There are several novel agents approved for the treatment relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T (peri-CAR-T). We conducted a multicenter retrospective analysis for the purpose of describing peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n=514) from thirteen centers treated with CAR-T for aggressive B-NHL between 2015-2021 were included. Clinical characteristics, CAR-T outcomes and treatment regimens administered pre- and post-CAR-T were collected. Survival curves were constructed using Kaplan Meier method. Multivariate Cox regression was used to determine the impact of variables on survival outcomes. For all patients receiving CAR-T, a greater number lines of therapy prior to CAR-T apheresis and receipt of bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). From time of CAR-T infusion, median PFS and OS were 7.6 and 25.6 months (n=514). From time of progression post-CAR-T (n=254), median OS was 5.5 months. The median PFS of treatments given in the first-line post-CAR-T failure (n=167) was just 2.8 months. Patients with refractory disease at day 30 had inferior OS and were less likely to receive subsequent treatment(s) compared to other patients with CAR-T failure. AlloHCT for select patients at any time following CAR-T failure (n=16) led to durable responses in over half at one-year. These data provide a benchmark for future clinical trials in patients with progression post-CAR-T, an unmet clinical need.

PURPOSE Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

Central nervous system (CNS) involvement in Burkitt lymphoma (BL) poses a major therapeutic challenge, and the relative ability of contemporary regimens to treat CNS involvement remains uncertain. We described prognostic significance of CNS involvement and incidence of CNS recurrence/progression after contemporary immunochemotherapy using real-world clinicopathologic data on adults with BL diagnosed between 2009 and 2018 across 30 US institutions. We examined associations between baseline CNS involvement, patient characteristics, complete response (CR) rates, and survival. We also examined risk factors for CNS recurrence. Nineteen percent (120/641) of patients (age 18-88 years) had CNS involvement. It was independently associated with HIV infection, poor performance status, involvement of ≥2 extranodal sites, or bone marrow involvement. First-line regimen selection was unaffected by CNS involvement (P=0.93). Patients with CNS disease had significantly lower rates of CR (59% versus 77% without; P

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: “ibrutinib responders”—patients who achieved complete or partial response (CR/PR) to ibrutinib; “stable disease (SD)”; and “primary progressors (PP)”—patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23–7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03–8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17–37.62, p p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.

Background. BL is a rare, high-grade B-cell lymphoma that is often studied in trials with small sample sizes. Historical definitions of "low-risk BL" vary between studies, use arbitrary cutoffs for lactate dehydrogenase (LDH), and identify a small favorable group, leaving >80-90% of patients (pts) in an undifferentiated "high-risk" category. A validated prognostic index will help compare study cohorts and better define good-prognosis pts for whom reduced treatment would be appropriate vs a poor-prognosis group in need of new approaches. Herein, we constructed and validated a simplified prognostic model for BL applicable to diverse clinical settings across the world. Methods. We derived the BL-IPI from a large real-world evidence cohort of US adults treated for BL in 2009-2018 (Evens A, Blood 2020). Progression-free survival (PFS) from diagnosis until BL recurrence, progression, death, or censoring was the primary outcome. We first determined the best prognostic cutoffs for age, LDH (normalized to local upper limit normal, ULN), hemoglobin (Hgb), and albumin. Independent risk factors were ascertained by forward stepwise selection into Cox regression from candidate variables: age, sex, HIV+ status, ECOG performance status (PS) ≥2, advanced stage (3/4), involvement of >1 extranodal site, bone marrow, central nervous system (CNS), values of LDH, Hgb, and albumin. Derivation models used multiple imputation to mitigate bias from missing data and reported hazard ratios (HR) with 95% confidence interval (CI). BL-IPI groups, defined by inspection of survival curves, were compared using log-rank test for trend. We validated performance of the BL-IPI in an external retrospective dataset of BL pts treated contemporaneously in centers from the United Kingdom, Scandinavia, Canada, and Australia. Results. Characteristics of pts in the derivation (N= 633) and validation (N=457) cohorts are shown in the Table. Age ≥40 years (yr), LDH >3xULN, Hgb 3xULN, low Hgb, and low albumin were associated with inferior PFS in univariate tests. In the multivariable model age ≥40 yr, LDH >3xULN, PS ≥2, and CNS involvement were selected as 4 independent prognostic factors; adding stage did not enhance the model. The model was simplified to 3 groups with 0 (low risk; 18% of pts), 1 (intermediate risk; 36% of pts; HR=3.14; 95%CI, 1.61-6.14), or 2-4 factors (high risk; 46% of pts; HR=6.52; 95%CI, 3.48-12.20; Fig A) with 3 yr PFS of 92%, 72%, and 53%, respectively (P Among pts with stage III/IV (historically classified as "high-risk" and constituting 78% of all pts in the cohort), the BL-IPI further discriminated subgroups with 3 yr PFS of 87%, 71%, and 52%, respectively (P In the international validation cohort, fewer pts had CNS involvement; most received CODOX-M/IVAC+R; and PFS/OS estimates at 3 yr were higher. BL-IPI categories were of similar size (low-risk 15%, intermediate-risk 35%, high-risk 50%), and provided similar risk discrimination (Harrell's C=.65 in both datasets). PFS at 3 yr was 96%, 82%, and 63%, respectively (P Conclusions. BL-IPI is a novel prognostic index specific to BL, which was validated to allow for simplified stratification and comparison of risk distribution in geographically diverse cohorts. The index identified a low-risk group with PFS >90-95%, which could be targeted with future strategies for treatment de-escalation. Conversely, only about 55-60% of pts in the high-risk group achieved cure with currently available immunochemotherapy. Disclosures Olszewski: Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Jakobsen:Takeda: Honoraria. Collins:ADC Therapeutics: Consultancy, Honoraria; Celleron: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Research Funding; BeiGene: Consultancy; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Pfizer: Honoraria; Celgene: Research Funding. Cwynarski:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Atara: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau. Bachanova:Incyte: Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; FATE: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Danilov:Abbvie: Consultancy; BeiGene: Consultancy; Nurix: Consultancy; Celgene: Consultancy; Gilead Sciences: Research Funding; Takeda Oncology: Research Funding; Pharmacyclics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Astra Zeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Research Funding; Karyopharm: Consultancy; Aptose Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; Rigel Pharmaceuticals: Consultancy. Diefenbach:Trillium: Research Funding; Millenium/Takeda: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; Denovo: Research Funding. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Farooq:Kite, a Gilead Company: Honoraria. Feldman:Pfizer: Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Cell Medica: Research Funding; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Viracta: Research Funding; Trillium: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Eisai: Research Funding; Kyowa Kirin: Consultancy, Research Funding. Gerrie:AbbVie: Consultancy, Honoraria, Research Funding; Astrazeneca: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Sandoz: Consultancy. Jagadeesh:Regeneron: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; MEI Pharma: Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees. Kamdar:BMS: Consultancy; Abbvie: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Speakers Bureau. Karmali:Takeda: Research Funding; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Karyopharm: Honoraria; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Khan:Seattle Genetics: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria; Bristol Myers Squibb: Research Funding; Celgene: Research Funding. Klein:Takeda: Membership on an entity's Board of Directors or advisory committees. Lossos:Verastem: Consultancy, Honoraria; Stanford University: Patents & Royalties; Seattle Genetics: Consultancy, Other; Janssen Biotech: Honoraria; NCI: Research Funding; Janssen Scientific: Consultancy, Other. Lunning:ADC Therapeutics: Consultancy; Legend: Consultancy; Acrotech: Consultancy; AstraZeneca: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding. Martin:I-MAB: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Sandoz: Consultancy; Bayer: Consultancy; Beigene: Consultancy; Cellectar: Consultancy; Incyte: Consultancy; Kite: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy. Martinex-Calle:Abbvie: Other: Travel grant. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Palmisiano:Genentech: Research Funding; AbbVie: Research Funding. Phillips:Beigene: Honoraria; Roche: Research Funding. Phillips:Seattle Genetics: Consultancy; Incyte: Consultancy, Other: travel expenses; AstraZeneca: Consultancy; Karyopharm: Consultancy; Beigene: Consultancy; Bayer: Consultancy, Research Funding; BMS: Consultancy; Pharmacyclics: Consultancy; Abbvie: Consultancy, Research Funding; Cardinal Health: Consultancy. Portell:Roche/Genentech: Consultancy, Research Funding; Infinity: Research Funding; Bayer: Consultancy; Amgen: Consultancy; TG Therapeutics: Research Funding; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; Xencor: Research Funding; BeiGene: Consultancy, Research Funding. Reddy:Celgene: Consultancy; BMS: Consultancy, Research Funding; Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy. Yazdy:Abbvie: Consultancy; Genentech: Research Funding; Octapharma: Consultancy; Bayer: Honoraria. Smith:Bristol Meyers Squibb: Research Funding; Ayala: Research Funding; Seattle Genetics: Research Funding; Portola: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Incyte: Research Funding; Ignyta: Research Funding; Genentech: Research Funding; De Novo Biopharma: Research Funding; AstraZeneca: Consultancy; Millenium/Takeda: Consultancy; Beigene: Consultancy; Bayer: Research Funding; AstraZeneca: Research Funding; Acerta Pharma BV: Research Funding; Karyopharm: Consultancy. Cheah:Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding; Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria. El-Galaly:F. Hoffmann-La Roche: Current Employment, Other: Support of parent study and funding of editorial support. Evens:Research To Practice: Honoraria, Speakers Bureau; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

Background Socioeconomic factors including race, ethnicity, and poverty level have been associated with disparities in survival among adult patients with acute leukemia. Insurance status is also likely to affect survival outcomes in these patients but has not been well studied. We investigated the impact of insurance status at time of diagnosis on survival in adult patients with acute lymphoblastic leukemia (ALL). Patients and Methods Adult patients diagnosed with B-lineage ALL between January 1, 2007 and October 31, 2017 were included, with follow-up through January 19, 2018. Kaplan-Meier survival curves were used to estimate overall survival (OS) and progression-free survival (PFS) for the 2 groups. Cox proportional hazard regression methods were used for univariate and multivariate analyses. Results A total of 136 patients were included in the study, 29 without insurance and 107 with insurance at time of diagnosis. Patients without insurance were younger and more likely to be Hispanic or Latino compared with insured patients. When controlling for confounding variables, patients without insurance had worse PFS. There was no statistically significant difference in OS between the 2 groups. Hispanic or Latino ethnicity was associated with improved PFS and OS in multivariate analyses. Conclusions Adult patients with ALL without health insurance at time of diagnosis had worse PFS when controlling for other relevant clinical factors. Lack of insurance may be an obstacle to timely, effective maintenance therapy in the outpatient setting. Further research is needed to understand how insurance status impacts survival and ways to mitigate any disparities.

Atypical response patterns following immune checkpoint blockade (ICB) in Hodgkin lymphoma (HL) led to the concept of continuation of treatment beyond progression (TBP); however, the longitudinal benefit of this approach is unclear. We therefore performed a retrospective analysis of 64 patients treated with ICB; 20 who received TBP (TBP cohort) and 44 who stopped ICB at initial progression (non-TBP cohort). The TBP cohort received ICB for a median of 4.7 months after initial progression and delayed subsequent treatment by a median of 6.6 months. Despite receiving more prior lines of therapy, the TBP cohort achieved longer progression-free survival with post-ICB treatment (median, 17.5 months vs. 6.1 months, p = .035) and longer time-to-subsequent treatment failure, defined as time from initial ICB progression to failure of subsequent treatment (median, 34.6 months vs. 9.9 months, p = .003). With the limitations of a retrospective study, these results support the clinical benefit of TBP with ICB for selected patients.

Metabolic dysfunctions enabling increased nucleotide biosynthesis are necessary for supporting malignant proliferation. Our investigations indicate that upregulation of fatty acid synthase (FASN) and de novo lipogenesis, commonly observed in many cancers, are associated with nucleotide metabolic dysfunction in lymphoma. The results from our experiments showed that ribonucleotide and deoxyribonucleotide pool depletion, suppression of global RNA/DNA synthesis, and cell cycle inhibition occurred in the presence of FASN inhibition. Subsequently, we observed that FASN inhibition caused metabolic blockade in the rate-limiting step of the oxidative branch of the pentose phosphate pathway (oxPPP) catalyzed by phosphogluconate dehydrogenase (PGDH). Furthermore, we determined that FASN inhibitor treatment resulted in NADPH accumulation and inhibition of PGDH enzyme activity. NADPH is a cofactor utilized by FASN, also a known allosteric inhibitor of PGDH. Through cell-free enzyme assays consisting of FASN and PGDH, we delineated that the PGDH-catalyzed ribulose-5-phosphate synthesis is enhanced in the presence of FASN and is suppressed by increasing concentrations of NADPH. Additionally, we observed that FASN and PGDH were colocalized in the cytosol. The results from these experiments led us to conclude that NADP–NADPH turnover and the reciprocal stimulation of FASN and PGDH catalysis are involved in promoting oxPPP and nucleotide biosynthesis in lymphoma. Finally, a transcriptomic analysis of non-Hodgkin’s lymphoma (n = 624) revealed the increased expression of genes associated with metabolic functions interlinked with oxPPP, while the expression of genes participating in oxPPP remained unaltered. Together we conclude that FASN–PGDH enzymatic interactions are involved in enabling oxPPP and nucleotide metabolic dysfunction in lymphoma tumors.

Diffuse large B-cell lymphoma featuring overexpression of MYC and B-Cell Lymphoma 2 (double expressor lymphoma, DEL) is associated with poor outcomes. Existing evidence suggesting improved outcomes for DEL with the use of more intensive regimens than R-CHOP is restricted to younger patients and based on limited evidence from low patient numbers. We retrospectively evaluated the impact of intensive frontline regimens versus R-CHOP in a multicenter analysis across 7 academic medical centers in the United States. We collected 90 cases of DEL, 46 out of 90 patients (51%) received R-CHOP and 44/90 (49%) received an intensive regimen, which was predominantly DA-EPOCH-R. Treatment cohorts were evenly balanced for demographics and disease characteristics, though the intensive group had a higher lactate dehydrogenase (LDH, 326 vs. 230 U/L p = 0.06) and presence of B-symptoms (50% vs. 22%, p = 0.01) compared to the R-CHOP cohort. There was no difference in PFS (median 53 vs. 38 months, p = 0.49) or overall survival (67 vs. not reached months, p = 0.14) between the R-CHOP and intensive therapy cohorts, respectively. On multivariate analysis, intensive therapy was associated with a hazard ratio of 2.35 (95% CI 0.74-7.41), though this was not statistically significant. Additionally, a subgroup analysis of intermediate high-risk lymphoma defined by IPI ≥3 did not identify a difference in survival outcomes between regimens. We conclude that in our multi-center cohort there is no evidence supporting the use of intensive regimens over R-CHOP, suggesting that R-CHOP remains the standard of care for treating DEL.

Introduction: Treatment of older patients (pts) with PCNSL is challenging due to the prevalence of comorbidities, frailty, and complexities with delivery of chemotherapy (CT). The optimal induction CT and consolidation regimens for older PCNSL pts is unknown. Moreover, there are few large scale prognostication studies available, including analysis of geriatric assessments (GA). We analyzed detailed characteristics, treatment patterns and outcomes with prognostication across 17 academic centers. Methods: We conducted a large, RW retrospective study of newly diagnosed PCNSL pts (1/2008-1/2019) ages ≥ 60 years (yrs). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. We detailed Cumulative Index Rating Scale-Geriatric (CIRS-G) scores & other GAs. Univariate associations were derived via Cox model with variables p Results: Among 491 initial cases, n=450 cases were verified for diagnosis & follow-up. Clinical features included: median age 71 yrs (60-88); male 47%; elevated LDH 30%; creatinine clearance 1 site). Cerebral involvement predominated in 75% with deep structure involvement in 20% & cerebellum in 5%. CSF involvement was documented in 13% of pts (unchecked in 26%). For GA at diagnosis, the median CIRS-G score was 6 (range 0-27) and impaired self-care activities of daily living (ADLs) were noted in 36%. Furthermore, geriatric syndrome (ie, dementia, delirium, depression, and/or falls) was present in 45% of pts. Induction therapy included CT in 91% of pts (of whom 82% had rituximab (Rtx)) and radiation therapy (RT) in 8%. The most common chemotherapy regimens were: high-dose methotrexate (HD MTX) or HD MTX with Rtx (MR) in 38%; HD MTX/procarbazine/vincristine (MPV) +/- Rtx 30%; HD MTX/temozolomide/Rtx (MTR) 22%; Rtx alone 2%; and HD MTX/cytarabine/thiotepa/Rtx (MATRIX) in 2%. Median MTX dosing for all pts was 3.5 g/m2 (range 1-8 g/m2), and by 3 most common regimens (all g/m2): MTR 5.1; MR 5.4; MPV 3.1 (P With 42 month median follow-up (1-125), 3-yr PFS & OS for all pts were 38% & 52%, respectively (Fig 1A/1B). On MVA, factors associated with inferior PFS were: advancing age (continuous HR 1.05, P Conclusions: Older pts with PCNSL have suboptimal outcomes, with 2/3 progressing in the first several years. GA is an important prognostic tool, and could be used to stratify pts in future investigations. In addition, use of Rtx, increasing MTX dose, and the MTR regimen were associated with improved outcomes. Disclosures Reddy: Genentech: Research Funding; Abbvie: Consultancy; KITE Pharma: Consultancy; Celgene: Consultancy; BMS: Consultancy, Research Funding. Bachanova:Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; FATE: Research Funding; BMS: Research Funding; Incyte: Research Funding. Bond:Seattle Genetics: Honoraria. Goldlust:COTA: Other; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel; Tocagen: Membership on an entity's Board of Directors or advisory committees, Other: travel; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel, Research Funding, Speakers Bureau; Boston Biomedical: Consultancy; Cortice Bio: Consultancy, Other: travel; WEX: Consultancy, Other: travel. Spurgeon:Beigene: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Acerta: Research Funding; AstraZeneca: Research Funding; Genmab: Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Karmali:Takeda: Research Funding; Karyopharm: Honoraria; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Martin:Celgene: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Teneobio: Consultancy; Beigene: Consultancy; Cellectar: Consultancy; Incyte: Consultancy; Kite: Consultancy; Morphosys: Consultancy; Karyopharm: Consultancy, Research Funding; Regeneron: Consultancy. Smith:Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; FortySeven: Research Funding; Karyopharm: Consultancy, Research Funding; Pharmacyclics: Research Funding; BMS: Consultancy; Janssen: Consultancy; Celgene: Consultancy, Research Funding; Acerta: Research Funding. Rubenstein:Kymera: Research Funding. Kahl:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Pharmacyclics LLC: Consultancy; Roche Laboratories Inc: Consultancy; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding. Evens:Merck: Consultancy, Honoraria, Research Funding; Research To Practice: Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria, Research Funding; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Mylteni: Consultancy, Honoraria.

Background Primary CNS lymphoma (PCNSL) is a rare non-Hodgkin lymphoma that is often associated with immunosuppressed states. The Epstein-Barr Virus (EBV) may play a role in tumor pathogenicity in some cases. The objective of this study was to examine the patient characteristics, tumor pathology, and survival outcomes associated with EBV tumor status in patients with PCNSL. Methods This was a retrospective subset analysis from 17 academic medical centers that included 439 patients of ages 60 years and above with PCNSL (David K et al. ASH 2020). The associations between EBV status and clinical or demographical variables were tested by Fisher's exact test, Wilcoxon rank-sum test, or CMH trend test. Kaplan-Meier estimator was used to estimate survival probability. Survival difference between groups was tested by log-rank test for statistical significance. Confidence interval of survival rate was calculated using Greenwood's formula. Results A total of 247 patients with available EBV status were included in this analysis. Median age was 71 (range 60-84) and 44.5% were male. Notably, none of the patients were HIV-positive. Twenty-five patients (10.1%) had EBV positive tumors as detected by EBER (EBV-encoded RNA) in-situ hybridization or LMP1 immunohistochemistry (IHC), 17 of which were solid organ transplant (SOT)-related post-transplant lymphoproliferative disorders (PTLD) and 8 of which were not PTLD. All EBV-positive non-PTLDs were diffuse large B-cell lymphoma. Three (15%) SOT-related PTLDs were EBV-negative. Patient characteristics analyzed included age at diagnosis, sex, ECOG performance status, history of prior or concurrent malignancies, history of solid organ transplant or autoimmune disease, history of allogeneic stem cell transplant, and immunosuppressive treatment. Of these, only a history of solid organ transplant or autoimmune disease (P Tumor characteristics analyzed included expression of C-MYC, BCL2, CD5, cell of origin markers (BCL6, MUM1, CD10), and CD20 through IHC, C-MYC and BCL2 translocation through FISH, histology, and involvement of brain parenchyma, CSF, spinal cord, and eyes. EBV-positive tumors were associated with low C-MYC (p=0.047) and BCL6 (p=0.0006) expression on immunohistochemistry, but not other factors. There were no significant differences in tumor characteristics between those with EBV-positive PTLD and EBV-positive non-PTLD. Among patients with PTLD, 30% (n=6) did not receive primary chemotherapy, and the most common treatment regimens were high-dose methotrexate (HD-MTX) with or without rituximab (n=5) and rituximab alone (n=3). However, there was no significant difference in outcomes among PTLD patients who received chemotherapy or those who did not. Among EBV-positive non-PTLD patients, only 12.5% (n=1) did not receive primary chemotherapy and the most common treatment regimens were methotrexate/rituximab/temozolomide (n=3) and HD-MTX with or without rituximab (n=3). There was no difference in overall or progression free survival between patients with EBV-positive and EBV-negative tumors, or in outcomes among SOT-related PTLD patients regardless of EBV status. However, patients with EBV-positive non-PTLD PCNSL had better overall survival compared to patients with EBV-positive PTLD and EBV-negative tumors (p=0.033, Figure). Conclusions In this large observational study of older patients with PCNSL, the incidence of EBV positive tumors was overall low and was most commonly associated with SOT-related PTLD. Mycophenolate mofetil was the most common immunosuppressive medication. In those without PTLD, there were no patient or tumor factors that were associated with EBV status. Unexpectedly, non-PTLD EBV-positive PCNSL had superior outcomes to EBV-positive PTLD and EBV-negative PCNSL. Future studies of EBV-positive non-PTLDs are warranted to further evaluate the potential impact of EBV latency and the immune response on the tumor microenvironment. Disclosures Reddy: BMS: Consultancy, Research Funding; Celgene: Consultancy; Abbvie: Consultancy; Genentech: Research Funding; KITE Pharma: Consultancy. Bachanova:Karyopharma: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; FATE: Research Funding; Incyte: Research Funding; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bond:Seattle Genetics: Honoraria. Goldlust:Tocagen: Membership on an entity's Board of Directors or advisory committees, Other: travel; BMS: Membership on an entity's Board of Directors or advisory committees, Other: travel; WEX: Consultancy, Other: travel; Cortice Bio: Consultancy, Other: travel; Boston Biomedical: Consultancy; COTA: Other; Novocure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel, Research Funding, Speakers Bureau. Spurgeon:Gilead: Research Funding; Genentech: Research Funding; Cardinal Health: Honoraria; Bristol-Myers Squibb: Research Funding; VelosBio: Consultancy, Research Funding; Acerta: Research Funding; Janssen: Consultancy, Research Funding; AstraZeneca: Research Funding; Pharmacyclics: Consultancy; Beigene: Research Funding; Verastem: Research Funding; Genmab: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Karmali:AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Takeda: Research Funding; BeiGene: Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Naik:Celgene: Other: advisory board; Sanofi: Other: advisory board. Smith:Janssen: Consultancy; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; BMS: Consultancy; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding. Rubenstein:Kymera: Research Funding. Kahl:BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy. Evens:Abbvie: Consultancy, Honoraria; Research To Practice: Honoraria, Speakers Bureau; MorphoSys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria, Research Funding; Mylteni: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding. Martin:Kite: Consultancy; Morphosys: Consultancy; Regeneron: Consultancy; Incyte: Consultancy; Cellectar: Consultancy; Beigene: Consultancy; Bayer: Consultancy; I-MAB: Consultancy; Sandoz: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; Celgene: Consultancy.

Hodgkin lymphoma (HL) in older patients, commonly defined as ≥60 years of age, is a disease for which survival rates have historically been significantly lower compared with younger patients. Older HL patients appear to have different disease biology compared with younger patients, including increased incidence of mixed cellularity histology, Epstein-Barr virus–related, and advanced-stage disease. For prognostication, several studies have documented the significance of comorbidities and functional status in older HL patients, as well as the importance of achieving initial complete remission. Collectively, selection of therapy for older HL patients should be based in part on functional status, including pretreatment assessment of activities of daily living (ADL), comorbidities, and other geriatric measures (eg, cognition, social support). Treatment of fit older HL patients should be given with curative intent, regardless of disease stage. However, attention should be paid to serious treatment-related toxicities, including risk of treatment-related mortality. Although inclusion of anthracycline therapy is important, bleomycin-containing regimens (eg, doxorubicin, bleomycin, vinblastine, dacarbazine) may lead to prohibitive pulmonary toxicity, and intensive therapies (eg, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are too toxic. Brentuximab vedotin given sequentially before and after doxorubicin, vinblastine, and dacarbazine to fit, untreated advanced-stage older HL patients was recently shown to be tolerable and highly effective. Therapy for patients who are unfit or frail because of comorbidities and/or ADL loss is less clear and should be individualized with consideration of lower-intensity therapy, such as brentuximab vedotin with or without dacarbazine. Altogether, therapy for older HL patients should be tailored based upon a geriatric assessment, and novel targeted agents should continue to be integrated into treatment paradigms.

BACKGROUND Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse

We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale–Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

7515 Background: Primary refractory disease (PRD) and early relapse (ER) are predictors of poor prognosis in classic Hodgkin lymphoma (cHL). In this multicenter retrospective study, we describe outcomes of PRD and ER in pts with relapsed/refractory (R/R) cHL treated with salvage therapy (ST) and autologous stem cell transplant (ASCT). Methods: Of 14 sites, adult patients with R/R cHL who received ST and underwent ASCT were enrolled. PRD was defined as progression on frontline chemoimmunotherapy or within 6 months of diagnosis. ER was defined as relapse from 6 months-1 yr of diagnosis. Pts who relapsed >1 yr of diagnosis were called late relapses (LR). Study objectives were Overall response rates (ORR), CR rates, PFS, and OS. Results: Of 986 total pts, 160 had PRD, 365 had ER and 461 had LR. Significantly higher number of pts with PRD, but not ER, had bulky disease (41% vs 27%, p1 line of ST (44% vs 30% vs 23%, p

Pregnancy-associated lymphoma (PAL) is an uncommon entity that lacks detailed prospective data. It poses significant management challenges that incorporate maternal and fetal risks associated with treatment or delayed intervention. Herein, we review the current literature for the diagnosis, management, and supportive care strategies for PAL. Establishment of a multidisciplinary team, including hematology-oncology, maternal-fetal medicine, and neonatology, is critical in the management of PAL. For staging, ultrasound and MRI are preferred modalities with use of computerized tomography in select situations. Data for the safety and effectiveness of therapy for PAL is largely based on retrospective studies. The timing of lymphoma-directed antenatal systemic therapy depends on the trimester, gestational age, lymphoma subtype and aggressiveness, and patient wishes. Therapy in the first trimester is usually not advocated, while treatment in the second and third trimesters appears to result in similar outcomes for PAL compared with non-pregnant patients with lymphoma. An overarching goal in most PAL cases should be to plan for delivery at term (i.e., gestational age > 37 weeks). For supportive care, most antiemetics, including agents such as neurokinin-1 receptor antagonists, have been used safely during pregnancy. For prevention or treatment of infections, particular antibiotics (i.e., macrolides, cephalosporins, penicillins, metronidazole), antivirals (i.e., acyclovir, valacyclovir, famciclovir), and antifungals (amphotericin B) have demonstrated safety and with use of growth factors reserved for treatment of neutropenia (vs. primary prophylaxis). Therapy for PAL should be individualized with goals of care that balance maternal and fetal well-being, which should include a multidisciplinary care team and overall intent for term delivery in most cases.

We examined adults with untreated Burkitt lymphoma (BL) from 2009 to 2018 across 30 US cancer centers. Factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate Cox models. Among 641 BL patients, baseline features included the following: median age, 47 years; HIV+, 22%; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 to 4, 23%; >1 extranodal site, 43%; advanced stage, 78%; and central nervous system (CNS) involvement, 19%. Treatment-related mortality was 10%, with most common causes being sepsis, gastrointestinal bleed/perforation, and respiratory failure. With 45-month median follow-up, 3-year PFS and OS rates were 64% and 70%, respectively, without differences by HIV status. Survival was better for patients who received rituximab vs not (3-year PFS, 67% vs 38%; OS, 72% vs 44%; P < .001) and without difference based on setting of administration (ie, inpatient vs outpatient). Outcomes were also improved at an academic vs community cancer center (3-year PFS, 67% vs 46%, P = .006; OS, 72% vs 53%, P = .01). In multivariate models, age ≥ 40 years (PFS, hazard ratio [HR] = 1.70, P = .001; OS, HR = 2.09, P < .001), ECOG PS 2 to 4 (PFS, HR = 1.60, P < .001; OS, HR = 1.74, P = .003), lactate dehydrogenase > 3× normal (PFS, HR = 1.83, P < .001; OS, HR = 1.63, P = .009), and CNS involvement (PFS, HR = 1.52, P = .017; OS, HR = 1.67, P = .014) predicted inferior survival. Furthermore, survival varied based on number of factors present (0, 1, 2 to 4 factors) yielding 3-year PFS rates of 91%, 73%, and 50%, respectively; and 3-year OS rates of 95%, 77%, and 56%, respectively. Collectively, outcomes for adult BL in this real-world analysis appeared more modest compared with results of clinical trials and smaller series. In addition, clinical prognostic factors at diagnosis identified patients with divergent survival rates.

Older adults with Hodgkin lymphoma (HL), commonly defined as age ≥ 60 years, represent approximately 20% of the total HL population. Historically, they have significantly inferior outcomes compared with younger patients. The cause of this is multifactorial, including biologic differences (e.g., mixed cellularity and EBV-related disease); high incidence of advanced stage disease; and frequency of comorbidities and decreased organ reserve leading to poorer tolerability of therapy with increased toxicity, including treatment-related mortality. Pretreatment evaluation for older HL patients should entail a geriatric assessment (GA), with evaluation of functional status and comorbidities (e.g., geriatric cumulative illness rating scale, CIRS-G) to determine fitness. Furthermore, treatment selection should be based in part on GA, with fit older patients receiving curative chemotherapy-based regimens and unfit or frail patients considering less intensive or non-chemotherapy-based platforms. Additionally, there may be consideration for pre-phase of therapy (e.g., pulse steroids) in order to improve performance status. The inclusion of anthracycline therapy appears important, while bleomycin-containing regimens (e.g., ABVD) may be associated with prohibitive pulmonary toxicity, and intensive therapies such as BEACOPP are too toxic. benefit ratio/benefit ratio, a priori omission of bleomycin may also be considered (i.e., AVD), especially for patients older than 70 years of age. In addition, newer regimens for older HL patients integrating novel therapeutic agents into frontline treatment have emerged as effective and tolerable options. Data incorporating brentuximab vedotin sequentially before and after AVD chemotherapy represent the best-reported outcomes in older HL patients to date. In the relapsed/refractory setting, salvage chemotherapy regimens followed by autologous stem cell transplantation should be considered for fit patients, while less intensive treatment, including the use of novel targeted agents, is an option for unfit or frail patients. In this review, we examine the epidemiology, importance of GA, and current treatment options for older HL patients.

Patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment. Seventeen North American centres retrospectively queried records. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment. Secondary aims included progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Fifty-nine patients (68% aggressive NHL, 69% advanced disease) were included. Patients received a median of three therapies before CBT. Fifty-three (90%) discontinued CBT due to progression. Post-CBT regimens included chemotherapy (49%), targeted therapy (30%), clinical trial (17%), transplant conditioning (2%) and chimeric antigen receptor T cell (CAR-T) therapy (2%). The ORR to post-CBT treatment was 51%, with median PFS of 6·1 months. In patients with at least stable disease (SD) to post-CBT, the median DOR was significantly longer than to pre-CBT (310 vs. 79 days, P = 0·005) suggesting sensitisation. Nineteen patients were transplanted after post-CBT therapy. Median overall survival was not reached, nor affected by regimen. Prospective trials are warranted, as this may offer R/R NHL patients a novel therapeutic approach.

Introduction The treatment of aggressive B-cell NHL has evolved rapidly over the last 5 years, owing to the FDA approval of 3 CD19 CAR T-cell constructs (CARTs) along with other novel targeted therapies. Real world practice data suggest that CARTs have been successfully administered in populations typically excluded from clinical trials. However, data on how to best utilize novel targeted agents as a pathway to CARTs and feasibility of CARTs in rare histologies remains limited. This retrospective multicenter study describes patient (pt) selection and practice patterns in pts treated with CD19 CARTs and provides insight on feasibility of CARTs in special populations. Methods Adult pts with R/R aggressive B-cell NHL treated with CD19 CARTs between 2015- 2020 across 12 US academic centers were identified. Data on demographic and clinical characteristics, disease and toxicity outcomes were collected. Univariate analyses (UVA) were performed to determine impact of demographic/clinical variables on survival. Survival curves were calculated using Kaplan-Meier method. Subgroup analysis was performed for pts with secondary central nervous system lymphoma (sCNSL). Results Clinical and demographic features were recorded from 400 pts (Table 1). Median age was 59 years (range 18-84). Of 271 pts with immunohistochemistry data, 79 (29%) had double-expressor lymphoma. Of 178 pts with FISH data captured, 62 (35%) had double/triple-hit lymphoma. Most common histological subtypes included 271 (68%) pts with de novo DLBCL, 81 (20%) with transformed FL, 13 (3%) with Richter's syndrome, and 8 (2%) with PMBCL. Rare histologies included 7 (2%) with transformed MZL, 5 (1%) with PTLD and 2 (0.5%) with grey zone lymphoma. 24 (6%) pts had sCNSL at time of CART apheresis. Two (0.5%) pts were HIV-positive. Median number of lines of therapy prior to CART was 2 (range 1-8); 182 (46%) pts received ≥ 3 lines. 114 (28%) pts previously had an autologous stem cell transplant. Targeted therapies used as salvage regimens at any point prior to CART are listed in Table 2: commonly used salvage targeted therapies included lenalidomide based therapy (imids, n=37, 9%), BTK inhibitors (BTKis, n=30, 8%), checkpoint inhibitors (CBIs, n=17, 4%) and polatuzumab-containing regimens (n=10, 3%). 2 (1%) pts received loncastuximab, and no pts received tafasitamab. Six (1.5%) pts proceeded to CART despite complete response to most recent pre-CART therapy. 191 (48%) pts received bridging between apheresis and CART infusion, choice of bridging noted in Table 2: the majority received chemotherapy (n=103, 54%); 28 (15%) received radiation (XRT); 25 (13%), 24 (13%) and 18 (9%) pts received imids, polatuzumab-containing regimens, or BTKis, respectively. With median follow-up of 22.4 months (mo) for the overall group, median (m) PFS was 11 mo (n=363); mOS, was 27 mo (n=397; Fig 1). Pts with sCNSL had a mPFS and mOS of 2 and 4 mo, respectively (Fig 1). On UVA, factors predicting poorer PFS and OS in the overall group included ≥3 pre-CART lines (p For outcomes according to bridging regimens: mPFS after CART for most commonly used systemic bridging therapies was 86 days (d) for platinum-based chemotherapy, 77 d for imids, 90 d for BTKis, 98 d for polatuzumab-bendamustine/rituximab, and 274 d for XRT. Median PFS for XRT bridging (274 d) was statistically better when compared to mPFS for listed systemic therapies combined (p Conclusion Survival outcomes with CARTs in our data set are consistent with those reported in clinical trial settings. CARTs are utilized in real world practice in rare subsets of aggressive R/R B-cell NHL not routinely included in clinical trials. Despite early data suggesting pts with sCNSL benefit from CART, our data suggest outcomes with CART are dismal in this group. Targeted therapies including imids, polatuzumab, BTKis and CBIs are feasible choices for salvage and/or bridging as a pathway to CARTs. Bridging with XRT resulted in improved mPFS post CART as compared to bridging with systemic therapies and suggests differences in pt selection for each with systemic therapies likely favored in those with more widespread disease burden. Minimal use of CD19-targeted agents pre-CART is attributed to later approval of these agents and concern for potential loss of CD19 antigen leading to CART resistance. Figure 1 Figure 1. Disclosures Cohen: Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy; Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding. Shouse: Kite Pharma: Speakers Bureau; Beigene: Honoraria. Hess: ADC Therapeutics: Consultancy; BMS: Speakers Bureau. Stephens: Beigene: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Epizyme: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Arqule: Research Funding; Mingsight: Research Funding; JUNO: Research Funding; Celgene: Consultancy; CSL Behring: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ma: Loxo: Research Funding; AstraZeneca: Honoraria, Research Funding, Speakers Bureau; Juno: Research Funding; Beigene: Research Funding, Speakers Bureau; Abbvie: Honoraria, Research Funding; Janssen: Research Funding, Speakers Bureau; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding, Speakers Bureau. Winter: BMS: Other: Husband: Data and Safety Monitoring Board; Actinium Pharma: Consultancy; Janssen: Other: Husband: Consultancy; Gilead: Other: Husband: Consultancy; Agios: Other: Husband: Consultancy; Epizyme: Other: Husband: Data and Safety Monitoring Board; Merck: Consultancy, Honoraria, Research Funding; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Karyopharm (Curio Science): Honoraria. Gordon: Zylem Biosciences: Patents & Royalties: Patents, No royalties; Bristol Myers Squibb: Honoraria, Research Funding. Danilov: Astra Zeneca: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Gilead Sciences: Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Rigel Pharm: Honoraria; Bayer Oncology: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding. Shah: Umoja: Consultancy; Legend: Consultancy; Kite: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Incyte: Consultancy. Barta: Seagen: Honoraria; Daiichi Sankyo: Honoraria; Acrotech: Honoraria; Kyowa Kirin: Honoraria. Epperla: Genzyme: Honoraria; Karyopharm: Other: Ad Board; Beigene: Speakers Bureau; Verastem: Speakers Bureau. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Karmali: Epizyme: Consultancy; BeiGene: Consultancy, Speakers Bureau; EUSA: Consultancy; Roche: Consultancy; AstraZeneca: Speakers Bureau; Morphosys: Consultancy, Speakers Bureau; Karyopharm: Consultancy; Takeda: Research Funding; BMS/Celgene/Juno: Consultancy, Research Funding; Janssen/Pharmacyclics: Consultancy; Genentech: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau.

Introduction: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) after autologous stem cell transplant (ASCT); yet studies comparing novel ST with conventional salvage chemotherapy are lacking. In a single center cohort, we demonstrated that bendamustine/brentuximab (BBV) had higher overall response rates (ORR) and complete response (CR) rates in ASCT-eligible R/R cHL (Desai et al JCO, 2021). Herein we report comparative outcomes of novel and conventional ST in R/R cHL who undergo ASCT, in a large multicenter retrospective cohort. Methods: Consecutive R/R cHL pts who underwent ASCT at 12 institutions across United States were included. Demographics and clinical variables at relapse including age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year) were recorded by electronic health records review. Study objectives were ORR, CR to first ST, post-ASCT PFS and OS by final ST. Time to event endpoints were defined from date of ASCT. Results: From 12 participating institutions, 853 pts of R/R cHL who underwent ASCT were eligible for this study. Median age was 33 (14-72) years, 457 (54%) were male, 446 (52%) had BD, 257 (30%) had advanced stage, 271 (32%) had END, 369 (43%) had B symptoms, 142 (17%) had PRD and 307 (36%) had ER. All 853 received at least 1 ST, 245 received 2 ST, 71 received 3 ST and 26 received 4 ST. Seven groups of ST were identified: 1. Conventional platinum-based chemotherapy (PBC) group including ICE, DHAP and ESHAP 2. BBV 3. Brentuximab Vedotin and nivolumab (BV/Nivo) 4. BV alone (BV) 5. gemcitabine-based chemotherapy (Gem) 6. checkpoint inhibitors (CPI) and 7. other miscellaneous agents (Misc). 1st ST was as follows: 553 had PBC; 69 had BBV; 48 had BV/Nivo; 65 had BV; 49 had Gem; 4 had CPI and 63 had Misc. There was no significant difference in the baseline characteristics by type of 1 st ST (data not shown). BBV had significantly higher ORR (92% vs 79%, p Final ST prior to ASCT was PBC in 451, BBV in 76, BV/Nivo in 48, BV in 87, CPI in 24, Gem in 90 and Misc in 64. Table 1 lists K-M estimates of 2-year survival probabilities for different Final ST groups. Median follow up was 3 (range 0.1-13) years. BV/Nivo group had significantly higher proportion of patients with PRD and BD than PBC, no other differences in baseline characteristics were identified amongst ST groups (data not shown). BV/Nivo (HR: 0.1 (CI 95:0.02-0.4), p 536 pts underwent ASCT in CR, 273 underwent ASCT in partial response (PR) and 31 underwent ASCT with progressive disease (PD). Pre-ASCT PR (HR 1.6 (CI 95:1.3-2.6), p In pts with pre-ASCT CR, all 36 who had pre-ASCT CR after BV/Nivo were alive and relapse free for follow up of 0.1-5 yrs. BV/Nivo was associated with significantly higher PFS (HR 0.1 (CI 95: 0.01-0.7), p Conclusions: BV/Nivo has a higher CR rate and better post-ASCT PFS compared to conventional chemotherapy and can lead to durable remissions in pts with pre-ASCT CR. BBV had a higher response rate and similar post-ASCT survival to conventional chemotherapy. BV had lower response rates compared to chemotherapy. Novel ST such as BV/Nivo and BBV may be preferable to conventional chemotherapy in R/R cHL. Figure 1 Figure 1. Disclosures Spinner: Notable Labs: Honoraria. Bachanova: FATE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; KaryoPharma: Membership on an entity's Board of Directors or advisory committees; Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dorritie: SITC presentation: Honoraria; Genmab: Research Funding; University of Pittsburgh/UPMC Hillman Cancer Center: Current Employment; Janssen: Research Funding; F. Hoffman-La Roche Ltd: Research Funding; Juno/BMS: Research Funding; Kite, a Gilead Company: Research Funding; OncLive/Institutional Perspectives on Cancer presentation: Honoraria. Arai: Magenta Therapeutics: Research Funding. Maurer: Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Diefenbach: Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; IMab: Research Funding; Morphosys: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding; Perlmutter Cancer Center at NYU Langone Health: Current Employment; AbbVie: Research Funding; IGM Biosciences: Research Funding; Incyte: Research Funding; Trillium: Research Funding; Gilead: Current equity holder in publicly-traded company; MEI: Consultancy, Research Funding. Nowakowski: Kyte Pharma: Consultancy; Ryvu Therapeutics: Consultancy; Selvita: Consultancy; Curis: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; MorphoSys: Consultancy; Bantham Pharmaceutical: Consultancy; Daiichi Sankyo: Consultancy; Zai Labolatory: Consultancy; Incyte: Consultancy; Kymera Therapeutics: Consultancy; TG Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Nanostrings: Research Funding. Advani: Astellas/Agensys: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Cell Medica: Membership on an entity's Board of Directors or advisory committees; Forty Seven: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutical: Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Kyowa: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Millenium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy; Regeneron: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees.

Background: Chemoimmunotherapy is considered standard initial therapy for follicular lymphoma (FL) with high tumor burden (HTB). Obinutuzumab and Bendamustine (OB) with maintenance Obinutuzumab (mO) is considered a standard therapy for the frontline treatment of HTB FL (GALLIUM, Marcus et al, NEJM 2017). Venetoclax (VEN), an oral BCL2 inhibitor, is an attractive target in FL given the high BCL2 expression; though single agent activity has been disappointing (Davids et al. JCO 2017). BCL2 inhibition is thought to be synergistic with chemotherapy. Thus, the PrE0403 study evaluated the OB-VEN combination in frontline HTB FL. Here we present end of induction (EOI) outcomes. Methods: The primary objective of this Phase II study was to estimate the complete remission (CR) rate at EOI. Potential participants must have had a histologically confirmed diagnosis of FL grade 1, 2, or 3a with HTB defined by GELF or high risk defined by FLIPI-1 criteria. They must have had adequate performance status and organ function. Notably, creatinine clearance must have been ≥50 mL/min. Participants must have not had prior treatment for FL. Eligible participants were treated with Bendamustine IV 90 mg/m2 Day (D) 1 & 2, Obinutuzumab IV 100 mg D1, 900 mg D2, 1000 mg D8 and D15 of Cycle (C) 1 then D1 of each cycle, and VEN 800 mg orally daily D1-10 every 28 days for 6 total cycles. Due to a high rate of laboratory tumor lysis syndrome (TLS) during C1 in the first 21 patients, VEN was removed from C1 and given in C2-6 only. Participants with a CR at EOI were treated with mO IV 1000 mg D1 every 8 weeks for 2 years. Those with a partial response (PR) or stable disease (SD) were treated with mO as well as VEN 800 mg orally daily for 2 years. Pneumocystis jiroveci Pneumonia (PJP) and antiviral prophylaxis was required as was G-CSF support. Response was assessed via Lugano Criteria at EOI including PET/CT and bone marrow assessment. Adverse Events (AEs) were evaluated using CTCAE v5.0. To be considered promising, OB-VEN should improve the null hypothesis CR rate of 50% (OB) to 65%. With an 85% power and a one sided 15% type I error, 56 participants would be needed with an estimated 51 eligible. Support for the study was from Genentech, Member of the Roche Group. Results A total of 56 participants were enrolled and treated between 12/2017 and 11/2020; baseline characteristics are listed in Table 1. TLS was closely monitored in C1 and 8/21 participants developed TLS when VEN was administered in C1; 0/35 when it was not. However, monitoring for TLS in C1 became less stringent when VEN was not administered. Treatment related Grade ≥3 toxicities occurred in 47/56 participants (83.9%) with serious adverse events in 31 of 56 (55.5%). Atypical infections were seen; there was one treatment related death on study due to cytomegalovirus (CMV) encephalitis as well as PJP pneumonia which occurred after induction C6. Enrollment was temporarily suspended and CMV monitoring was implemented with no further occurrences. Another participant receiving mO later developed BK virus nephropathy following mO C6 and now requires ongoing hemodialysis. Another was diagnosed with Respiratory Syncytial Virus pneumonia 30 days after C6 and later PJP pneumonia after C2 of mO. Common (incidence >10%) AEs during induction are listed in Table 2. 45 of 56 (80.4%) participants were able to receive all 6 cycles of OB-VEN. CR was seen in 41 of 56 participants (73.2%, 2 sided 95% Confidence Interval (CI) 59.7-84.2%) at the EOI. 30 participants (53.5%) went onto maintenance. With a median follow up of 20.9 months, estimated 2 year Overall Survival (OS) and Progression-Free Survival (PFS) (90% CI) is 94.4% (82.4-98.3%) and 85.8% (68.8-93.9%) respectively. Conclusions This Phase II study of OB-VEN in untreated HTB FL showed high CR rate and met its primary endpoint with early signs of prolonged PFS. Laboratory TLS was identified but it was unclear if attributed solely to VEN, as baseline laboratory TLS rate for OB is unknown. The rate of Grade ≥3 AE of 83.9% (compared to 69% for OB in GALLIUM, Hiddeman JCO 2018) and the observation of opportunistic infections including CMV encephalitis, PJP pneumonia and BK nephropathy, suggests the combination is highly immunosuppressive. Therefore, while the study met its primary outcome, the combination of OB-VEN at 800 mg for 10 days, plus mO, does not have an acceptable risk/benefit profile. Participants will continue to be followed for efficacy and safety during the maintenance phase. Figure 1 Figure 1. Disclosures Portell: Acerta/AstraZeneca: Research Funding; SeaGen: Research Funding; Pharmacyclics: Honoraria; Xencor: Research Funding; Aptitude Health: Honoraria; BeiGene: Honoraria, Research Funding; Abbvie: Research Funding; TG Therapeutics: Honoraria, Research Funding; Kite: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Morphosys: Honoraria; Targeted Oncology: Honoraria; Genentech: Research Funding; VelosBio: Research Funding. Nowakowski: MorphoSys: Consultancy; Incyte: Consultancy; Kymera Therapeutics: Consultancy; TG Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Nanostrings: Research Funding; Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Zai Labolatory: Consultancy; Daiichi Sankyo: Consultancy; Bantham Pharmaceutical: Consultancy; Curis: Consultancy; Karyopharm Therapeutics: Consultancy; Selvita: Consultancy; Ryvu Therapeutics: Consultancy; Kyte Pharma: Consultancy. Cohen: Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy; Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding. Kahl: AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding; AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy. OffLabel Disclosure: Venetoclax is not approved for follicular lymphoma or in combination with bendamustine and obinutuzumab

Background: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is a highly active therapy for relapsed/refractory (R/R) aggressive B-cell lymphoma. Nonetheless, most patients (pts) ultimately develop progressive disease (PD). There is little guidance on the optimal treatment approach(es) for these pts. We performed a multicenter retrospective analysis with a primary objective to assess treatment patterns and outcomes in pts with R/R aggressive B-cell lymphoma who develop PD after anti-CD19 CARTs. Methods: Pts with aggressive B-cell lymphoma treated with anti-CD19 CART between 2015 and 2020 across 12 US academic medical centers were included. Demographic and clinical characteristics were collected along with CART toxicities and response. Regimens administered as salvage post CART were assessed. Univariate analyses (UVA) were performed to determine impact of demographic and clinical variables on survival outcomes. All p-values were two-tailed. Survival curves were calculated using the Kaplan-Meier method. Results: A total of 400 pts received anti-CD19 CARTs and were included for analysis. For the entire cohort: median PFS and OS from time of CART infusion were 11 months [mo] and 27 mo respectively. On log-rank testing, pts who received ≥3 lines of pre-CART therapy and those with refractory disease pre-CART had significantly worse PFS (p=0.004 & 0.001) and OS (both p With median follow-up 22.4 mo, 190 pts (48%) had PD after CART; demographic and clinical variables of pts with and without PD are detailed in Table 1. Biopsy to confirm PD and assess CD19 status was done in 69 pts (36%) with CD19 negative relapse seen in 11 (16%). Of pts with PD, median PFS and OS from time of PD was 83 days (in pts who received salvage) and 174 days (for all PD pts) respectively. Pts with PD were more likely to have elevated LDH (p=0.001) and extranodal disease (p=0.003) at apheresis. For pts with PD after CART: 125 (65.5%) received further therapies. Pts were more likely to receive salvage therapies if their best response to CART was CR (p=0.026) or PR (p=0.015). Response rates of select first- and second-line therapies and PFS of first line therapies received after CART failure are detailed in figure 1. ORR and CRs were highest for polatuzumab, bendamustine, & rituximab (pola-BR; 73% & 40%), followed by BTK inhibitors (BTKi; 50% & 38%), and bispecific antibodies (bsAb) (50% & 25%). Five of 7 pts who received a BTKi had non-germinal center (GC) cell of origin (COO; 1 unknown COO). On log-rank testing, pts with elevated LDH (p=0.003) at time of apheresis and those with intermediate/high IPI (p=0.013) had inferior PFS with first salvage regimens. Median PFS was highest for pola-BR (4.5 mo, n=14), followed by bsAb (2.5 mo, n=8), lenalidomide +/- anti-CD20 antibody (1.8 mo, n=13), checkpoint inhibitors (CPI; 1.6 mo, n=10), BTKi (1.2 mo, n=8), radiation alone (1.2 mo; n=17), chemotherapy (1.1 mo, n=12), and tafasitamab + lenalidomide (0.9 mo, n=5). Median PFS for all treated pts was 1.8 mo. OS from start of first salvage regimen was highest for CPI (OS 12.4 mo, n=10), followed by pola-BR (8.9 mo, n=14), BTKi (8.8 mo, n=8), lenalidomide +/- anti-CD20 (8.7 mo, n=13), radiation alone (7.1 mo, n =17), bsAb (5.9 mo, n=8), chemotherapy (5.4 mo, n=12), and tafasitamab + lenalidomide (1.2 mo, n=5). 12 pts (6.3%) later received an allogeneic hematopoietic cell transplant (alloHCT). In alloHCT pts at last follow-up, 10 were evaluable for response: 7 had CR and 5 remain in CR. Clinical characteristics of pts who received alloHCT are detailed in table 2. Notably, median age was 59 years (41-68), 1 (8.3%) had a prior alloHCT, and 6 (50%) had prior autologous HCT. The majority had CR or PR as best response to CART (CR n=6, 50%; PR n=3, 25%), and only 1 pt (8.3%) with PD as best response to CART was salvaged with alloHCT. Conclusions: This is the largest reported analysis to date of pts with aggressive B-cell lymphoma who develop PD post-CART. The highest ORRs were with pola-BR, bsAb, and BTKi as first line of salvage. High response rates with BTKi may be attributed to non-GC COO in the majority of treated pts and perhaps a beneficial immunomodulatory effect on previously administered CARTs. AlloHCT remains a potential curative therapy for select pts with over half with durable remission; however, few ultimately received alloHCT. Despite increased use of novel therapies, survival in pts who progress after CART is still dismal warranting more effective therapies. Figure 1 Figure 1. Disclosures Epperla: Genzyme: Honoraria; Karyopharm: Other: Ad Board; Beigene: Speakers Bureau; Verastem: Speakers Bureau. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. Hess: ADC Therapeutics: Consultancy; BMS: Speakers Bureau. Cohen: Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy; Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding. Ma: Abbvie: Honoraria, Research Funding; Beigene: Research Funding, Speakers Bureau; Loxo: Research Funding; Juno: Research Funding; AstraZeneca: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; TG Therapeutics: Research Funding; Pharmacyclics: Research Funding, Speakers Bureau. Winter: Gilead: Other: Husband: Consultancy; Janssen: Other: Husband: Consultancy; Ariad/Takeda: Other: Husband: Data and Safety Monitoring Board; Epizyme: Other: Husband: Data and Safety Monitoring Board; Agios: Other: Husband: Consultancy; Actinium Pharma: Consultancy; BMS: Other: Husband: Data and Safety Monitoring Board; Merck: Consultancy, Honoraria, Research Funding; Novartis: Other: Husband: Consultancy, Data and Safety Monitoring Board; Karyopharm (Curio Science): Honoraria. Gordon: Zylem Biosciences: Patents & Royalties: Patents, No royalties; Bristol Myers Squibb: Honoraria, Research Funding. Danilov: Bayer Oncology: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Rigel Pharm: Honoraria; Takeda Oncology: Research Funding; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; SecuraBio: Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Gilead Sciences: Research Funding. Stephens: Adaptive: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; JUNO: Research Funding; Mingsight: Research Funding; CSL Behring: Consultancy; Novartis: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Arqule: Research Funding; Celgene: Consultancy; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shah: Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Umoja: Consultancy; Incyte: Consultancy; Kite: Consultancy; Legend: Consultancy; Epizyme: Consultancy; Lily: Consultancy, Honoraria, Research Funding. Shouse: Beigene Pharmaceuticals: Honoraria; Kite Pharmaceuticals: Speakers Bureau. Barta: Acrotech: Honoraria; Daiichi Sankyo: Honoraria; Seagen: Honoraria; Kyowa Kirin: Honoraria. Karmali: Karyopharm: Consultancy; EUSA: Consultancy; Roche: Consultancy; Janssen/Pharmacyclics: Consultancy; Genentech: Consultancy; Morphosys: Consultancy, Speakers Bureau; Epizyme: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Consultancy, Research Funding; AstraZeneca: Speakers Bureau; Takeda: Research Funding; BeiGene: Consultancy, Speakers Bureau.

Pro-inflammatory peptides present in wheat and related grains are associated with celiac disease and non-celiac gluten sensitivity. We hypothesize that these peptides induce enteric responses that may exacerbate the gastrointestinal manifestations of graft-versus-host disease after an allogeneic hematopoietic stem cell transplant. Therefore, we propose that a gluten free diet should be tested as a prophylactic and/or therapeutic intervention against gastrointestinal graft-versus-host disease for patients undergoing an allogeneic hematopoietic stem cell transplant.

The anti-tumor effects of allogeneic hematopoietic stem cell transplantation depend upon engraftment of donor cells followed by a graft-versus-tumor (GVT) effect. However, pre-clinical and clinical studies have established that under certain circumstances, anti-tumor responses can occur despite the absence of high levels of durable donor cell engraftment. Tumor response with little or no donor engraftment has been termed "microtransplantation." It has been hard to define conditions leading to tumor responses without donor cell persistence in humans because the degree of engraftment depends very heavily upon many patient-specific factors, including immune status and degree of prior therapy. Likewise, it is unknown to what degree donor chimerism in the blood or tissue is required for an anti-tumor effect under conditions of microtransplantation. In this review, we summarize some key studies supporting the concept of microtransplantation and emphasize the importance of recent large studies of microtransplantation in patients with acute myelogenous leukemia (AML). These AML studies provide the first evidence of the efficacy of microtransplantation as a therapeutic strategy and lay the foundation for additional pre-clinical studies and clinical trials that will refine the understanding of the mechanisms involved and guide its further development as a treatment modality.

Introduction Relapses involving the central nervous system (CNSrel) occur in ~5% of patients (pts) with aggressive non-Hodgkin lymphoma (NHL) in the rituximab era (Ghose et al, Clin LML 2015) with rates exceeding 10% in high risk groups (Villa et al, Ann Onc 2010; Schmitz et al, JCO 2016). CNSrel are generally thought to occur in the first 4-6 months from diagnosis. Prophylaxis (PPx) administration, route, and frequency are not standardized, and the impact of PPx on CNSrel risk is incompletely understood. Methods We performed a multicenter retrospective analysis of pts with aggressive NHL (excluding Burkitt's) without known CNS involvement (inv) who received single-route CNS PPx with during front-line (FL) anthracycline-based therapy (tx) from 2013-2019 across 19 US academic institutions. Recipients of chemotherapy for prior CLL or indolent NHL were ineligible. Method, frequency, and outcomes of CNS PPx administration were evaluated, with significance assessed by various statistical methods via two-tailed P Results 1030 patients were identified who met eligibility criteria. Clinical features included median age 61 years (yrs; range 16-86), 40.9% female, ECOG PS 0-1 82.8%, elevated LDH 65.3%, >1 extranodal (EN) site 42.3%, stage 3/4 disease 79.2%. NHL histologies included diffuse large B cell (DLBCL; 75.2%), high grade B cell (16.3%), transformed follicular lymphoma (5.6%) and 3% other; among pts with DLBCL, 46.4% had germinal center (GCB) subtype and 40.5% had non-GCB. 26.2% (n=210) of evaluable pts had double-hit lymphoma (DHL). Among pts with known HIV status, 7.2% (n=65) were HIV-positive. 85.7% had EN inv; common sites included bone (35.4%), liver (13.7%), gastrointestinal (12.7%), lung (11.8%), and marrow (11.5%). FL regimens included RCHOP (45.9%), REPOCH (46.5% total; 79.1% with dose-adjustment), 7.6% other. PPx was given intravenously (IV) in 20% of pts vs 77% intrathecally (IT), over a median 2.9 vs 4.1 doses respectively; see Table 1 for factors associated with PPx route. PPx was generally well-tolerated, with 10.7% PPx-related toxicity reported; see Table 2. CNSrel after FL tx was 5.3% overall without significant difference by PPx route (7% IV vs 5% IT, p=0.178). This lack of difference between PPx routes was observed in all subgroup analyses performed, including by: age, stage, histology, number of EN sites, individual EN site inv, elevated LDH, CNS-IPI, DHL status, HIV status, FL regimen, number of PPx doses. There was no significant difference in anatomic site(s) of CNSrel by PPx route. CNSrel occurred bimodally: 24% by end of FL tx vs 76% delayed (average 2.3 yrs, range 0.4-5.2 yrs). Rates of CNSrel were significantly higher with CNS-IPI high vs moderate risk (8.3 vs 4.1%, p=0.03; Figure 1), elevated LDH (6.9 vs 2.6%, p=0.007) and multiple inv EN sites (7.5% for 2+ vs 4% for 0-1, p=0.01); each additional EN site further increased risk (p=0.03 for trend; Figure 2). Increased CNSrel was noted in pts with testis (13.7 vs 5%, p=0.004) and liver inv (11.1 vs 4.6%, p=0.002) vs those without inv at respective sites. No significant difference was noted at other EN sites, including renal/adrenal (4.8 vs 5.6%, p=0.71), marrow (8.9 vs 5.1%, p=0.09), or lung (8.6 vs 5.1%, p=0.12). All EN site-CNSrel correlations were unchanged when accounting for PPx route. With median follow-up of 2.3 yrs, median PFS and OS for the overall group have not been reached; 2-yr PFS and OS were 70 and 85% respectively. PFS and OS were each predicted by CNS-IPI (p Conclusion Use of single-route ppx demonstrated similar CNSrel vs established outcomes for this population in the rituximab era, with no difference by PPx route. CNSrel remains a rare but devastating complication, with greater risk even after single-route PPx in those with higher EN burden and inv of key EN sites. Disclosures Kahl: Acerta: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche Laboratories Inc: Consultancy; Pharmacyclics LLC: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy; AstraZeneca Pharmaceuticals LP: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Spinner:Notable Labs: Honoraria. Advani:Celgene, Forty Seven, Inc., Genentech/Roche, Janssen Pharmaceutical, Kura, Merck, Millenium, Pharmacyclics, Regeneron, Seattle Genetics: Research Funding; Astra Zeneca, Bayer Healthcare Pharmaceuticals, Cell Medica, Celgene, Genentech/Roche, Gilead, KitePharma, Kyowa, Portola Pharmaceuticals, Sanofi, Seattle Genetics, Takeda: Consultancy. Voorhees:AstraZeneca: Research Funding. Grover:Genentech: Research Funding; Tessa: Consultancy. Huntington:Genentech: Consultancy; Novartis: Consultancy; Celgene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Honoraria; Bayer: Consultancy, Honoraria; DTRM: Research Funding; Astrazeneca: Honoraria; AbbVie: Consultancy. Spurgeon:Beigene: Research Funding; Gilead: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy, Research Funding; VelosBio: Consultancy, Research Funding; Cardinal Health: Honoraria; Verastem: Research Funding; Genmab: Research Funding; AstraZeneca: Research Funding; Acerta: Research Funding. Olszewski:Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding. Landsburg:Seattle Genetics: Speakers Bureau; Morphosys: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Curis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Triphase: Research Funding. Kamdar:Roche: Research Funding. Caimi:Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding; Verastem: Other: Advisory Board; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Celgene: Speakers Bureau. Karmali:Takeda: Research Funding; BeiGene: Speakers Bureau; AstraZeneca: Speakers Bureau; Karyopharm: Honoraria; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau. Stephens:Pharmacyclics: Consultancy; Innate: Consultancy; Verastem: Research Funding; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; Gilead: Research Funding; Arqule: Research Funding; Juno: Research Funding; MingSight: Research Funding; Acerta: Research Funding; Beigene: Consultancy. Smith:Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding; TG Therapeutics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Khan:Celgene: Research Funding; Pharmacyclics: Honoraria; Seattle Genetics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Honoraria. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Portell:Bayer: Consultancy; Xencor: Research Funding; BeiGene: Consultancy, Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; TG Therapeutics: Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding.

Introduction Ibrutinib was FDA approved for relapsed or refractory (R/R) marginal zone lymphoma (MZL) based on a phase II clinical trial that showed an overall response rate of 48% (Noy et al, Blood 2017). However, factors associated with response to ibrutinib in R/R MZL and outcomes of patients after progression on ibrutinib are unknown. Given the poor survival in other B-cell lymphomas such as mantle cell lymphoma (MCL) after progression on ibrutinib (Martin P et al, Blood 2016), we sought to evaluate clinicopathologic characteristics predictive of ibrutinib failure in R/R MZL, and describe outcomes of patients who experienced progression on ibrutinib therapy. Methods We performed a multicenter retrospective study of MZL patients treated at 19 US medical centers. Eligible patients were ≥ 18 years diagnosed with MZL from 2010-2019, who received ibrutinib for R/R MZL. Patients achieving a complete response (CR) or partial response (PR) with ibrutinib were considered ibrutinib responders, while those who had stable disease (SD) or progression of disease (PD) were classified as non-responders. The primary endpoint was to evaluate factors predictive of primary progression (PD) on ibrutinib. Secondary endpoints include evaluation of predictors of overall survival (OS) and progression-free survival (PFS) following ibrutinib therapy, assessment of outcomes based on the sequencing of ibrutinib therapy, and evaluation of outcomes following ibrutinib failure. PFS was defined as time from the start of ibrutinib therapy until lymphoma relapse/progression or death from any cause, censoring at last clinical assessment if no progression or death. OS was defined as time from the start of ibrutinib treatment until death or last follow-up. A multivariable Poisson regression analysis was performed to model ibrutinib progression on the clinicopathologic factors (see Table). To identify significant predictors for OS and PFS, we used a multivariable Cox model. Results 101 patients with R/R MZL received ibrutinib, of whom 99 had sufficient data for inclusion in the analysis. Among these patients, 63% (n=62) had CR/PR to ibrutinib (ibrutinib responders, CR=17, PR=45) and 37% (n=37) had no response (ibrutinib non-responders, SD=25, PD=12). The median duration of follow-up was 1.8 years (range=0.1-5.4 years) and 2 years (range=0.2-6.3 years) for ibrutinib responders and non-responders, respectively. Baseline characteristics of the R/R MZL patients stratified by ibrutinib response are shown in the Table. Among all the baseline factors examined for association with ibrutinib progression, only primary refractory disease (refractory to frontline therapy, RR=3.78, 95%CI=1.36-10.45, p=0.01) was predictive of a higher probability of primary progression on ibrutinib on multivariable analysis. The median OS was significantly better for responders (NR [not reached], 95%CI=3.2-NR) compared to non-responders (3.4 years, 95%CI=1.4-NR) (Figure 1A). Achieving CR/PR with ibrutinib (HR=0.22, 95%CI=0.09-0.52) and lack of complex cytogenetics (HR=0.22, 95%CI=0.08-0.59) were predictors of superior PFS. Similarly, ibrutinib response (HR=0.13, 95%CI=0.03-0.53) and lack of complex cytogenetics (HR=0.19, 95%CI=0.04-0.87) were predictors of better OS. There was no difference in PFS or OS based on the timing of ibrutinib administration (second vs third vs fourth line and beyond, Figure 1B and 1C). The median post ibrutinib relapse/progression OS (PROS) for patients who initially responded then progressed on ibrutinib (secondary progression, n=19) was 4 years (Figure 1D). The median PROS for patients who had no response to ibrutinib were stratified according to SD vs PD. The median PROS for those who had SD was NR and those with PD was 0.1 year (Figure 1E). Conclusion This is the largest series of R/R MZL patients treated with ibrutinib. A history of primary refractory disease was predictive of primary progression on ibrutinib, while the presence of complex cytogenetics was associated with inferior PFS and OS. In contrast to MCL, the outcomes of patients who progress on ibrutinib in R/R MZL are not poor except for the primary progression cohort (those with PD as the best response to ibrutinib). Improving therapeutic options for patients who experience PD with ibrutinib treatment represents an urgent unmet need and these patients should be prioritized for evaluation of novel therapeutic approaches. Figure Disclosures Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Reddy:Genentech, BMS: Research Funding; KITE Pharma, Abbvie, BMS, Celgene: Consultancy. Caimi:Genentech: Research Funding; Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding. Greenwell:Lymphoma Research Foundation: Research Funding; Acrotech Biopharma LLC, Kyowa Kirin: Consultancy. Janakiram:Takeda, Fate, Nektar: Research Funding. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Awan:Genentech: Consultancy; Janssen: Consultancy; Astrazeneca: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Dava Oncology: Consultancy; Celgene: Consultancy; Blueprint medicines: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy. Barta:Monsanto: Consultancy; Atara: Honoraria; Seattle Genetics: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria. Grover:Genentech: Research Funding; Tessa: Consultancy. Bartlett:Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed Therapeutics: Research Funding; Acerta: Consultancy; BTG: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Merck: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding; BMS/Celgene: Research Funding. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Herrera:Pharmacyclics: Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Karyopharm: Consultancy.

Ixazomib activity and transcriptomic analyses previously established in T cell (TCL) and Hodgkin (HL) lymphoma models predicted synergistic activity for histone deacetylase (HDAC) inhibitory combination. In this present study, we determined the mechanistic basis for ixazomib combination with the HDAC inhibitor, belinostat, in HL and TCL cells lines (ixazomib-sensitive/resistant clones) and primary tumour cells. In ixazomib-treated TCL and HL cells, transient inhibition followed by full recovery of proteasomal activity observed was accompanied by induction of proteasomal gene expression with NFE2L2 (also termed NRF2) as a prominent upstream regulator. Downregulation of both NFE2L2 and proteasomal gene expression (validated by quantitative real time polymerase chain reaction) occurred with belinostat treatment in Jurkat and L428 cells. In addition, CRISPR/Cas9 mediated knockdown of NFE2L2 in Jurkat cells resulted in a significant decrease in cell viability with ixazomib compared with untreated control cells. Using transcriptomic and proteasomal activity evaluation of ixazomib, belinostat, or ixazomib + belinostat treated cells, we observed that NFE2L2, proteasome gene expression and functional recovery were abrogated by ixazomib + belinostat combination, resulting in synergistic drug activity in ixazomib-sensitive and -resistant cell lines and primary cells. Altogether, these results suggest that the synergistic activity of ixazomib + belinostat is mediated via inhibition NFE2L2-dependent proteasomal recovery and extended proteasomal inhibition culminating in increased cell death.

Nuclear factor kappa B (NF-κB) is constitutively expressed in many primary acute myelogenous leukemia (AML) and leukemic stem cell (LSC) samples. Inhibition of nuclear NF-κB ex vivo results in cyto...

In 2007, Tulsa Community College (TCC) joined the national Achieving the Dream (ATD) network, which is dedicated to developing data-informed interventions to increase persistence and completion among community college students. TCC’s participation in the national initiative set it down a path for positive institutional change, but it was the College’s restructuring of their internal work teams and their process improvements since 2011–2012 that have resulted in a sustainable system that will help retain knowledge and ensure successful leadership transitions. In 2013, TCC rebranded its modified ATD system as Completing the Dream, combining the goals of Complete College America with the action research principles of Achieving the Dream. Because of these efforts, the College is in a stronger position today than it has ever been to serve our students using evidence-based strategies, ultimately resulting in more college-educated citizens in the Tulsa area.

Policy, financial, and transportation barriers have limited participation in dual enrollment for marginalized (low-socioeconomic, first-generation, and ethnic minority) students in Oklahoma. This chapter presents a collaborative effort by education and community leaders that has successfully eliminated these barriers and increased the number of marginalized students participating in dual enrollment.

Introduction: Historically, outcomes for BL have improved in adults using dose intensive chemotherapy regimens and early CNS prophylaxis. More recent data using a less intensive regimen, DA-EPOCH, have been reported. We analyzed detailed patient (pt) & disease characteristics and treatment patterns across 26 US CCs over a recent 9 year (yr) period and also determined survival rates & prognostication. Methods: We conducted a large multicenter retrospective study of newly diagnosed (dx) adult BL pts (6/2009 - 6/2018). Dx was established by institutional expert pathology review; all cases were verified for BL based on 2016 WHO criteria (high grade B cell lymphoma, BL like, etc were excluded). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. Univariate (UVA) associations were derived via Cox model with variables P ≤0.05 entered stepwise into a multivariate (MVA) model. Using significant factors from the MVA, a prognostic survival model was constructed. Results: Among N=557 verified BL cases, clinical features included: median age 47 yrs (17-88 yrs; 24% ≥60 yrs); male 76%; HIV+ 22%; ECOG PS 0/1 76%; B symptoms 51%; elevated LDH 78% (3, 5, & 10x elevation: 44%, 29% & 15%, respectively); hemoglobin 1 EN 43%; and 76% stage 3-4 disease (10% stage 1). Additionally, 16% and 3% of pts had baseline leptomeningeal (CSF or cranial nerve palsy) or parenchymal CNS involvement, respectively (see Zayac A et al. ASH 2019 for details). For MYC partner, 68% had t(8;14), 4% light chain, 5% negative FISH (otherwise classic BL) and 23% + break apart probe. HIV+ pts had several clinical differences: CSF+ 23% vs 12% P=0.003; CNS 19% vs 8% P1 EN 60% vs 38% P For all pts, 87% had Tx at an academic CC (13% at community CC). Tx regimens were: CODOX-M/IVAC (Magrath) 31%, HyperCVAD/MA 29%, DA-EPOCH 28%, other 10% (mostly CHOP-based & CALGB Tx) & 1% were never treated. 90% of pts received rituximab as part of Tx (69% inpatient (inpt) & 31% outpatient) & 2% had consolidative autologous SCT. Response among all pts were CR 72%, PR 6%, SD 1%, PD 14%, 7% not evaluable. The treatment related mortality (TRM) rate across all pts was 8.9% (HIV+ vs not: 13% vs 8% P=0.09); most common: sepsis 48%, GI bleed/perforation 14% & respiratory failure 12%. TRM by Tx: hyperCVAD/MA 11.5%, EPOCH 6.4%, Magrath 6.3% & other 18.9%. With 39 month median follow-up, 3 year progression-free survival (PFS) and overall survival (OS) were 65% and 72%, respectively (Fig 1A). Among all pts who experienced disease progression, 90% occurred For prognostication, outcomes were inferior for pts ages ≥40 yrs & LDH >3x normal (Fig 1B/C). Notably, survival rates were not different based on HIV status (Fig 1D) or by the 3 most common Tx regimens (Fig 1E). However, there were important Tx differences based on presence of CNS involvement (see Zayac A et al. ASH 2019). Additionally, use of rituximab was associated with improved PFS & OS (Fig 1F), while outcomes were similar whether rituximab was given inpt vs outpatient (inpt PFS HR 1.25, P=0.19). Furthermore, Tx at an academic CC was associated with improved outcomes, which persisted on MVA (PFS HR 0.54, 95%CI 0.33-0.88 P=0.01; OS HR 0.50, 95%CI 0.29-0.87 P=0.01) & achievement of initial CR was strongly prognostic (Fig 1G). Baseline factors significant on UVA for PFS & OS were: age ≥40 yrs; PS 2-4; LDH >3x; anemia, low albumin; BM involvement; Stage 3-4; CSF+; & >1 EN. On MVA, factors associated with inferior survival were: age ≥40 yrs (PFS HR 1.57, P3x (PFS HR 2.28, P Conclusions: Outcomes for adult BL in this contemporary, large, multicenter RW analysis appear inferior to smaller published series. Interestingly, despite increased adverse prognostic factors, survival rates appeared similar in HIV+ pts. In addition, use of rituximab, achievement of initial CR, and Tx at an academic CC were associated with improved survival. Finally, a novel BL-specific survival model identified pts with markedly divergent outcomes. Disclosures Evens: Seattle Genetics: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Tesaro: Research Funding; Verastem: Consultancy, Honoraria. Danilov:Janssen: Consultancy; Seattle Genetics: Consultancy; MEI: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; Janssen: Consultancy; TG Therapeutics: Consultancy; Curis: Consultancy; Pharmacyclics: Consultancy; Aptose Biosciences: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement , Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Meyers Squibb: Research Funding; MEI: Research Funding; Gilead Sciences: Consultancy, Research Funding; Abbvie: Consultancy; Bristol-Meyers Squibb: Research Funding. Reddy:KITE Pharma: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; Genentech: Research Funding; Abbvie: Consultancy. Farooq:Celgene: Honoraria; Kite Pharma: Research Funding. Khan:Janssen: Other: Educational Content/Symposium; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Other: Research Funds; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Yazdy:Genentech: Research Funding; Bayer: Honoraria; Abbvie: Consultancy; Octapharma: Consultancy. Karmali:Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution. Martin:Janssen: Consultancy; Teneobio: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy. Diefenbach:LAM Therapeutics: Research Funding; Incyte: Research Funding; Genentech: Consultancy, Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Feldman:Eisai: Research Funding; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Roche: Research Funding. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Naik:Celgene: Other: Advisory board. Kamdar:Celgene: Consultancy; AstraZeneca: Consultancy; Seattle Genetics: Speakers Bureau; University of Colorado: Employment; Pharmacyclics: Consultancy. Portell:AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Amgen: Consultancy. Olszewski:Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Genentech: Research Funding; Adaptive Biotechnologies: Research Funding. Alderuccio:Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; Foundation Medicine: Other: Immediate family member; Targeted Oncology: Honoraria; Inovio Pharmaceuticals: Other: Immediate family member; OncLive: Consultancy.

Background: Autologous stem cell transplantation (ASCT) can be curative for patients (pts) with relapsed/refractory Hodgkin lymphoma (HL) who are sensitive to salvage therapy, particularly for pts who achieve a complete metabolic response (CMR) before ASCT. Pts who fail multiple salvage regimens have inferior outcomes and are generally considered poor candidates for ASCT. Recent studies suggest that anti-PD-1 monoclonal antibodies (mAbs) may restore sensitivity to cytotoxic therapy in HL pts with previously chemorefractory disease. We hypothesized that PD-(L)1 mAb-based salvage therapy may therefore also improve ASCT outcomes for HL pts who had failed salvage therapy. Methods: Medical records were reviewed at 13 US transplant centers to identify pts with a diagnosis of classic HL who failed at least 2 systemic therapies, were treated with a PD-1 or PD-L1 mAb (either alone or in combination) as 3rd line or later therapy, and subsequently underwent ASCT. Results: 44 eligible pts were identified. The median age was 33 (range 19-68). Pts received ABVD (39), AVD (2), brentuximab vedotin (BV) + AVD (1), Stanford V (1), or eBEACOPP (1) as 1st line therapy. 26 pts (59%) were refractory to 1st line treatment and 8 additional pts (18%) relapsed within 12 months. High-risk clinical features were observed frequently at 1st relapse including extranodal involvement (47%), B symptoms (27%), and advanced stage (64%). Pts received PD-(L)1 based treatment after failing 2 lines (32%), 3 lines (57%), or ≥4 lines (11%) of therapy. 32 pts (73%) were refractory to the line of therapy before PD-(L)1, 25 pts (57%) to 2 consecutive lines before PD-(L)1, and 10 pts (22%) to 3 consecutive lines before PD-(L)1. 16 pts (36%) were refractory to ≥2 salvage therapies immediately before PD-(L)1 therapy and 17 (39%) were refractory to all prior treatments. 39 pts (89%) received BV or a BV-based combination before ASCT. 67% were BV-refractory, including 86% of those receiving BV monotherapy. Pts received a median of 6 doses of a PD-(L)1 mAb (range 2-26) either as monotherapy (75%) or as part of a PD-1 based combination (25%). The median time from last dose of PD-(L)1 mAb to ASCT was 54 days (range 12-386). Best response to PD-(L)1-based therapy was CR (53%), PR (33%), SD (12%), or PD (2%). The median number of systemic therapies (including PD-(L)1) before ASCT was 4 (range 3-7) and 12 pts (27%) received intervening salvage therapy between PD-(L)1 treatment and ASCT. Pre-ASCT PET status was CR in 31 pts (70%), PR in 9 (18%), SD in 4 (9%), and PD in 1 (2%). There were no ASCT-related deaths. 2 pts developed BCNU pneumonitis and 1 developed engraftment syndrome. All 3 pts responded to steroids. 14 pts (32%) have received maintenance therapy with BV (4), a PD-1 mAb (8), or BV + PD-1 mAb (2). 4 pts (9%) received consolidative radiation. With a median post-ASCT follow-up of 12.2 months, progression-free survival (PFS) at 1 yr was 91% [95CI 75-97]. Notably, resistance to chemotherapy before PD-(L)1 therapy did not predict worse post-ASCT outcomes (see Table). 1-yr PFS was 90% for pts who were refractory to the 3 lines of therapy before PD-(L)1, 93% for pts refractory to ≥2 salvage therapies immediately before PD-(L)1, and 90% for pts refractory to all prior treatments. Favorable 1-yr PFS was also seen among pts who received PD-(L)1 as 4th or later line therapy (88% vs 100% for pts receiving PD-[L]1 as 3rd line, p=0.17) and among pts who failed to achieve a CMR on pre-ASCT PET (1-yr PFS 81% vs 96% for CMR pts, p=0.34). Lack of response to PD-(L)1 therapy (1-yr PFS 67% vs 96%, p=0.04), receipt of intervening salvage therapy (1-yr PFS 72% vs 100%, p=0.026), and increasing age (HR 1.11, p=0.015) were all significant predictors of inferior PFS. 1-yr overall survival was 100%. Conclusions: This high-risk cohort is heterogenous in terms of number of prior therapies and degree of chemoresistance, but excellent post-ASCT outcomes were observed among even the most heavily pre-treated, chemorefractory subgroups. Outcomes for PD-(L)1 responders were particularly favorable with a 1-yr PFS of 96%, suggesting that response to PD-(L)1 rather than prior chemotherapy may be the more important predictor of post-ASCT outcomes in this pt population. While longer follow-up is required to confirm the durability of these remissions, ASCT can be considered for HL pts responding to PD-(L)1 based salvage therapy, even if they have previously demonstrated a high degree of chemoresistance. Table Disclosures Nieto: Novartis: Research Funding; Astra-Zeneca: Research Funding; Affimed: Research Funding; Affimed: Consultancy. Byrne:Karyopharm: Research Funding. Maddocks:BMS: Research Funding; Novartis: Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding. Svoboda:BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. McGuirk:Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Research Funding; Fresenius Biotech: Research Funding; Astellas: Research Funding; Bellicum Pharmaceuticals: Research Funding. Advani:Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Millennium: Research Funding; Janssen: Research Funding; Cell Medica, Ltd: Consultancy; Regeneron: Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stanford University: Employment, Equity Ownership; Agensys: Research Funding; Kura: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding; Infinity Pharma: Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; LAM Therapeutics: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; ASH: Research Funding; Lymphoma Research Foundation: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy. Frigault:Xenetic: Consultancy; Foundation Medicine: Consultancy; Novartis: Consultancy; Nkarta: Consultancy; Juno/Celgene: Consultancy; Kite/Gilead: Honoraria; Incyte: Consultancy. Chen:Magenta: Consultancy; Takeda: Consultancy; Incyte: Consultancy; Kiadis: Consultancy; Abbvie: Consultancy. Lynch:Johnson Graffe Keay Moniz & Wick LLP: Consultancy; Rhizen Pharmaceuticals S.A: Research Funding; Juno Therapeutics: Research Funding; Takeda Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; T.G. Therapeutics: Research Funding. Smith:Seattle Genetics: Research Funding; Denovo Biopharma: Research Funding; Ayala (spouse): Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Incyte Corporation: Research Funding; Ignyta (spouse): Research Funding; Genentech: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Armand:Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sigma Tau: Research Funding; Infinity: Consultancy; Otsuka: Research Funding; Genentech: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Herrera:Merck: Consultancy; BMS: Consultancy; Genentech: Research Funding; Adaptive Biotechnologies: Consultancy; Gilead Sciences: Research Funding; KiTE/Gilead: Consultancy; Genentech: Consultancy; Merck: Research Funding; Astra-Zeneca: Research Funding; Seattle Genetics: Consultancy; BMS: Research Funding; Seattle Genetics: Research Funding.

Background: BL is associated with a high risk of primary or secondary CNS involvement, warranting intrathecal (IT) and/or systemic therapy that penetrates the blood-brain barrier (BBB). The lower-intensity DA-EPOCH-R regimen has recently shown high survival rates in BL (Dunleavy, NEJM 2013), but it omits drugs traditionally used for CNS prophylaxis (like high-dose methotrexate [HDMTX]). The objective of this multi-institutional retrospective study was to examine treatments, risk factors, and CNS-related outcomes among patients (pts) with BL. Methods: We collected data from 26 US centers on adult BL pts diagnosed (dx) in 6/2009-6/2018. Using institutional expert pathology review and 2016 WHO criteria, we excluded other high-grade lymphomas (including BL-like/unclassifiable), or cases with inadequate clinicopathologic data. We studied factors associated with baseline CNS involvement (CNSinv) using logistic regression reporting odds ratios (OR). Progression-free (PFS), overall survival (OS), and cumulative incidence function of CNS recurrence (in a competing risk analysis) were examined in Cox or Fine-Gray models reporting hazard (HR) or subhazard ratios (SHR), respectively. All estimates report 95% confidence intervals (in square brackets). Results: Among 557 BL pts (median age, 47 years [yr], 24% women, 23% HIV+), 107 (19%) had CNSinv at dx, including 89 (16%) with leptomeningeal, and 15 (3%) with parenchymal CNS disease. In a multivariable model, factors significantly associated with CNSinv at dx included stage 3/4 (OR, 11.2 [1.47-85.9]), poor performance status (PS; OR, 2.12 [1.22-3.69]), ≥2 extranodal sites (OR, 3.77 [2.02-7.03]), or marrow involvement (OR, 2.44 [1.35-4.39]), whereas intestinal involvement conferred low risk of CNSinv (OR, 0.27 [0.11-0.65]). CNSinv at dx was not significantly associated with use of specific chemotherapy regimens (Fig. A,P=.75) or receipt of IT chemotherapy (91% vs 84%, P=.065). Pts with CNSinv were less likely to achieve a complete response (62% vs 76%, P=.005), had worse 3 yr PFS (47% vs 69%; P3x upper limit of normal [LDH>3x]; see Evens AM et al, ASH 2019 for further details). With median follow up of 3.6 yrs, 33 pts (6%) experienced a CNS recurrence (82% within 1 yr from dx; 79% purely in CNS, and 21% with concurrent systemic BL). The cumulative risk of CNS recurrence was 6% [4-8%] at 3y (Fig. D). Univariate significant predictors of CNS recurrence included baseline CNSinv, HIV+ status, stage 3/4, poor PS, LDH>3x, involvement of ≥2 extranodal sites, marrow, or testis. However, in a multivariate model only baseline CNSinv (SHR, 3.35 [1.53-7.31]) and poor PS (SHR, 2.24 [1.03-4.90]) retained significance. The 3 yr risk of CNS recurrence varied from 3% for pts with no risk factor, to 10% with one, and 17% with both factors (Fig. E). In addition, the risk of CNS recurrence differed according to chemotherapy regimen, and was significantly higher for pts treated with DA-EPOCH (12% at 3y [8-18%]; Fig. F) compared with CODOX-M/IVAC (4% [2-8%]) or hyperCVAD/MA (3% [1-6%]; SHR for DA-EPOCH vs. others, 3.50 [1.69-7.22]). All pts recurring after DA-EPOCH had received IT chemotherapy. Higher risk of CNS recurrence persisted with DA-EPOCH regardless of baseline CNSinv (Pinteraction=.70), poor PS (Pint=.14), or HIV status (Pint=.89). Baseline CNSinv was the strongest factor associated with CNS recurrence after DA-EPOCH (3 yr risk, 30% vs 8%, P Conclusions: In adult BL, baseline CNSinv and poor PS predicted subsequent CNS recurrence, an outcome that is associated with a dismal prognosis. Furthermore, treatment with DA-EPOCH was associated with a significantly increased risk of CNS recurrence in this real-world analysis. For BL pts with baseline CNSinv treated in routine clinical practice, regimens with highly BBB-penetrant drugs (e.g. CODOX-M/IVAC, hyperCVAD/MA) may be preferred. Studies should delineate ways to mitigate the risk of CNS recurrence with lower-intensity programs. Disclosures Evens: Seattle Genetics: Consultancy, Honoraria; Research to Practice: Honoraria; Verastem: Consultancy, Honoraria; Affimed: Consultancy, Honoraria; Pharmacyclics: Honoraria, Other: DMC; Bayer: Consultancy, Honoraria; Takeda: Research Funding; Merck: Research Funding. Smith:Incyte Corporation: Research Funding; Seattle Genetics: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Acerta Pharma BV: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Denovo Biopharma: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Ayala (spouse): Research Funding. Naik:Celgene: Other: Advisory board. Reddy:KITE Pharma: Consultancy; Abbvie: Consultancy; Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy. Farooq:Celgene: Honoraria; Kite Pharma: Research Funding. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Khan:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Educational Content/Symposium; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Other: Research Funds. Alderuccio:Puma Biotechnology: Other: Immediate family member; Agios: Other: Immediate family member; Inovio Pharmaceuticals: Other: Immediate family member; Targeted Oncology: Honoraria; OncLive: Consultancy; Foundation Medicine: Other: Immediate family member. Yazdy:Bayer: Honoraria; Genentech: Research Funding; Octapharma: Consultancy; Abbvie: Consultancy. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Karmali:Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution; Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau. Martin:Celgene: Consultancy; Teneobio: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy. Magarelli:Tevan Oncology: Speakers Bureau. Kamdar:Seattle Genetics: Speakers Bureau; Pharmacyclics: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; University of Colorado: Employment. Portell:Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; TG Therapeutics: Research Funding; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding. Olszewski:Genentech: Research Funding; Adaptive Biotechnologies: Research Funding; TG Therapeutics: Research Funding; Spectrum Pharmaceuticals: Research Funding.

Background: PCGTCL is a rare disorder, accounting for < 1% of all lymphomas. In part given the rarity, timely and accurate diagnosis (dx) remains challenging. Moreover, PCGTCL is typically characterized by a highly aggressive course. We conducted a multi-institutional, retrospective analysis to delineate pathology, patient (pt) characteristics, treatment patterns & outcomes of PCGDTCL in the modern era. Methods: We collected detailed information on pts with PCGDTCL dx between 2000 - 2017 across 10 academic centers. Pathologic data, including IHC & flow characteristics on de-identified pathology reports, were reviewed centrally by an expert dermatopathologist (MP). A pathologic tier was assigned to each case based on fidelity to the following pre-defined minimum criteria: flow cytometric evidence of gamma and/or delta protein-expressing lymphoma or histopathologic evidence of gamma and/or delta protein expression & at least 50% atypical lymphocytes positive for gamma/delta immunostain (IHC) with tissue representative of entire lesion. The presence of >25% CD30 positivity of malignant lymphocytes was an exclusion criterion. Further, PCR evidence of TCR gamma monoclonality or TCR beta/betaF1 negativity alone were inadequate for inclusion with confirmation of gamma/delta phenotype (especially IHC) being key for inclusion. A clinical tier was also assigned to each case based on group consensus. A composite score was derived by combining pathologic & clinical tiers, with those fitting a pre-determined score threshold included in the primary analysis. Univariate (UVA) associations were derived via Cox model for associations with survival. Results: Collectively, all centers submitted a total of 80 cases that were dx & treated locally as PCGDTCL. 48 (60%) cases met pre-defined criteria for inclusion of bona fide dx of PCGTCL. 26 (33%) cases had insufficient composite scores and were grouped in a 2nd tier & 6 cases had incomplete follow-up data and were unsuitable for analysis. The most common reason for placement in the 2nd tier was negativity for gamma/delta IHC or lack of documentation of such testing (n=16). Among the top tier of 48 veritable cases, 32 pts (67%) were male, 39 (81%) white & 4 (8%) black. Median age was 62 years (range 20-88). 19 (40%) pts had B symptoms at dx; ECOG performance status (PS) 0 in 12 pts (25%) & 1-3 in 22 cases (45%) (unknown 29%); anemia was present in 21 pts (44%) & LDH increased in 22 (46%). Bone marrow was involved in only 3 pts (6%) & hemophagocytic syndrome was present at dx in 6 pts (12%). Frontline therapy was heterogeneous (Table 1) with the most common therapies being bexarotene alone in 8 pts; UV therapy in 6 pts; and CHOP in 4 pts. Furthermore, there was inclusion of etoposide in 12 pts (25%), anthracyclines in 9 (19%) & platinum agents in 3 pts (6%). The overall response to 1st line therapy was 40% (19% complete response) with stable disease in 10%, progression in 35% & unknown in 15%. Seven pts (15%) received consolidative stem cell transplantation (SCT), which was allogeneic in all but 1 case. The 2-year PFS for the 48 bona fide pts was 39% (95% CI 0.26-0.59) (Fig 1A) & 2-year OS was 36% (95% CI 0.23-.56) (Fig 1B). The 26 cases in the 2nd tier had overall similar 2-year PFS of 41% (95% CI 0.15-67) and OS of 37% (95% CI 0.22-0.62). In terms of impact of therapy, use of consolidative SCT in 1st remission was associated with improved survival (P=0.02) (Fig 1C). No other therapeutic variable had significance. In UVA for baseline factors, PS (P=0.006) (Fig 1D) and increased vs. normal LDH (P=0.05) were significantly associated with OS. Median OS for pts with normal LDH was 25 months vs 12 months with increased LDH. Median OS for pts with ECOG PS 0 was not reached vs approximately 14 months for ECOG PS 1-3. Conclusions: To the best of our knowledge, this series represents one of the largest reported to date of PCGDTCL. Accurate diagnosis and classification of PCGDTCL need ongoing analysis and delineation. Using strict criteria, only 60% of cases across 10 academic centers were confirmed as bona fide PCGDTCL. Analysis of these pts treated in the modern era demonstrated modest survival. In addition, we identified several prognostic factors, in particular LDH and ECOG PS, associated with patient outcome. Furthermore, the incorporation of allogeneic SCT in 1st remission may contribute to improved long-term survival. Enhanced treatment options and continued collaboration are critically needed in this rare disease. Disclosures Bennani: Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board. Landsburg:Takeda: Research Funding; Takeda: Research Funding; Triphase: Research Funding; Seattle Genetics: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Haun:Karger, Inc.: Other: Royalties: Textbook. William:Techspert: Consultancy; Guidepoint Global: Consultancy; Defined Health: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Mehta-Shah:Kiowa Hakka Kirin: Consultancy; Celgene: Research Funding; Roche/Genentech: Research Funding; Bristol Myers Squibb: Research Funding; Verastem Pharmaceuticals: Research Funding; Innate Pharmaceuticals: Research Funding. Wilcox:Bristol-Myers Squibb: Research Funding; Millenium/Takeda: Research Funding; CTI Biopharma: Research Funding; Incyte: Research Funding. Feldman:AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Roche: Research Funding; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Cell Medica: Research Funding; Amgen: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Corvus: Research Funding. Evens:Tesaro: Research Funding; Pharmacyclics: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding. Horwitz:Affimed: Consultancy; Mundipharma: Consultancy; Forty-Seven: Research Funding; Astex: Consultancy; Aileron: Research Funding; Kyowa Hakko Kirin: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Trillium: Research Funding; Forty-Seven: Research Funding; Trillium: Research Funding; Portola: Consultancy; Kura: Consultancy; Celgene: Consultancy, Research Funding; Astex: Consultancy; Kyowa Hakko Kirin: Consultancy; Aileron: Research Funding; Portola: Consultancy; Kura: Consultancy; Kura: Consultancy; Miragen: Consultancy; Miragen: Consultancy; Portola: Consultancy; Innate Pharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Mundipharma: Consultancy; ADCT Therapeutics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Aileron: Research Funding; Forty-Seven: Research Funding; Miragen: Consultancy; Seattle Genetics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Kyowa Hakko Kirin: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADCT Therapeutics: Research Funding; Infinity/Verastem: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Affimed: Consultancy; Innate Pharma: Consultancy; Affimed: Consultancy; Astex: Consultancy; Trillium: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty-Seven: Research Funding; Mundipharma: Consultancy; Astex: Consultancy; Celgene: Consultancy, Research Funding; Innate Pharma: Consultancy; Kura: Consultancy; ADCT Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Miragen: Consultancy; Portola: Consultancy; Aileron: Research Funding; Kyowa Hakko Kirin: Consultancy; Affimed: Consultancy; Trillium: Research Funding; Millennium/Takeda: Consultancy, Research Funding.

Background: Rituximab combined with chemotherapy (R-chemotherapy) is the standard of care first-line treatment for diffuse large B-cell lymphoma (DLBCL). Despite success with R-chemotherapy, 30% to 50% of patients with high-risk DLBCL will relapse, and outcomes are poor among patients who relapse within one year of diagnosis. Given the challenge of successful salvage, novel first-line therapies are needed. Blinatumomab, a bispecific T-cell engager (BiTE®) antibody construct that directs cytotoxic T cells to lyse CD19-expressing B cells, has shown efficacy as salvage therapy in patients with relapsed or refractory DLBCL. This open-label, multicenter, phase 2 study (ClinicalTrials.gov, NCT03023878) assessed the efficacy and safety of blinatumomab after first-line R-chemotherapy for patients with newly diagnosed, high-risk DLBCL. Methods: Patients (≥18 y) had proven high-risk DLBCL (International Prognostic Index [IPI] 3−5 and double/triple hit or double MYC/BCL2 expressor) and Eastern Cooperative Oncology group performance status ≤2. To be eligible for blinatumomab, patients were required to achieve complete metabolic response (CMR), partial metabolic response (PMR), or stable metabolic response by PET/CT after a run-in period with 6 cycles of R-chemotherapy (R-CHOP, R-DA-EPOCH, or R-CHOEP). Blinatumomab was given by continuous intravenous infusion in a single 84-day cycle 1 (9 μg/day for 7 days, 28 μg/day for 7 days, and 112 μg/day for 42 days, followed by a 28-day treatment-free interval) and an optional 28-day cycle 2 (9 μg/day for 7 days, 28 μg/day for 7 days, and 112 μg/day for 14 days) for patients without progressive metabolic disease (PMD). The primary endpoint was the incidence and severity of adverse events (AEs). Additional endpoints were objective response rate (ORR [CMR + PMR]) per Lugano criteria, minimal residual disease (MRD) by plasma cell−free circulating tumor DNA, overall survival (OS), and pharmacokinetics (PK). Results: Of 47 patients enrolled, 17 (36%) discontinued R-chemotherapy run-in (protocol criteria, n=6; patient request, n=5; disease progression, n=3; ineligibility, n=1; AE, n=1; death, n=1) and 30 (64%) completed the run-in (2 did not proceed to blinatumomab). Of 28 patients who received blinatumomab, 26 (93%) had high or high-intermediate IPI; 8 (29%) were double/triple hit and 10 (36%) were double protein expressors (Table). In total, 26 (93%) patients completed cycle 1; ten of 11 (91%) patients completed optional cycle 2. Blinatumomab PK were consistent with those in previous studies. After the R-chemotherapy run-in before starting blinatumomab, 24 patients had objective metabolic responses and 4 had no metabolic response (NMR). After blinatumomab treatment, the ORR (within 12 weeks of starting blinatumomab) was 89% (25/28 patients; 95% CI, 72−98; Table). The 4 patients with NMR before blinatumomab had objective responses after blinatumomab treatment. Three patients with objective responses before blinatumomab relapsed after blinatumomab. Twenty-six (93%) patients were still alive with a median follow-up time of 8.6 months; 2 died (disease progression; n=1; infection not related to treatment, n=1). Nine of 13 (69%) patients during the R-chemotherapy run-in were MRD positive, all of whom converted to MRD negative after treatment with blinatumomab. After treatment with blinatumomab, 17 of 18 (94%) patients were MRD negative; the MRD positive patient had PMD. During blinatumomab treatment, 11 (39%) patients had grade ≥3 AEs, and 5 (18%) had grade ≥4 AEs. Two (7%) patients discontinued treatment due to AEs (grade 3 neurotoxicity; grade 4 neutropenia). Consistent with previous blinatumomab reports, neurologic events (NEs) were reported in 17 (61%) patients, including 3 (11%) with grade 3 NEs and 1 (4%) with NEs leading to treatment discontinuation. No patients had grade ≥3 cytokine release syndrome. Other grade ≥3 events of interest included neutropenia and febrile neutropenia (n=4; 14%) and infection (n=3; 11%). Conclusions: In patients with newly diagnosed, high-risk DLBCL, blinatumomab monotherapy after first-line R-chemotherapy led to an 89% ORR, and safety was consistent with that in earlier studies in DLBCL. Thus, blinatumomab is a potential treatment option for patients with newly diagnosed disease. Disclosures Katz: Stemline: Speakers Bureau; Dova: Consultancy. Chu:Celgene: Honoraria; Teva: Consultancy; AstraZeneca: Honoraria; Amgen Inc.: Honoraria; Gilead: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Morley:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: speaker fees, conference support ; TAKEDA: Other: conference support ; Janssen Pharmaceuticals: Other: speaker fees; ROCHE: Membership on an entity's Board of Directors or advisory committees, Other: conference support; ABBVIE: Other: speaker fees. Chen:Amgen Inc.: Employment, Equity Ownership. Kalabus:Amgen Inc.: Employment, Equity Ownership. Morris:Amgen: Employment, Equity Ownership. Anderson:Amgen Inc.: Employment, Equity Ownership. Avilion:Amgen Inc.: Employment, Equity Ownership. González-Barca:Takeda: Honoraria; Kiowa: Consultancy; Celtrion: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy; Roche: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.

INTRODUCTION Five year survival for adults diagnosed with Acute Lymphoblastic Leukemia (ALL) is approximately 30-40% and decreases with older age at diagnosis. Although survival rates have improved over the last few decades, identifying risk factors for worse survival remains critical to improving outcomes. Previous studies in Acute Myeloblastic Leukemia (AML) and ALL have demonstrated disparities in survival rates based on race, ethnicity and poverty level. Lack of health insurance may also negatively impact survival in acute leukemias by impeding access to therapy and delaying treatment initiation. These issues are particularly problematic for hematologic malignancies where the costs of multidrug chemotherapy, prophylactic drugs and allogeneic stem cell transplant (ASCT) are significant. Our study investigates survival outcomes in uninsured vs. insured adult patients with ALL at a single comprehensive cancer center. METHODS This study was an IRB-approved retrospective chart review of patients diagnosed with B-lineage ALL between January 1, 2007 and October 31, 2017 and treated on the adult leukemia service at our institution. Charts were reviewed for demographic, diagnostic, cytogenetic and molecular data, as well as treatment history and response. A total of 136 patients were included and follow up extended through January 19, 2018. Insurance status was determined at time of diagnosis and defined as any insurance (including public) versus no insurance. Differences between the two groups were assessed using chi-square tests. Cox proportional hazard regression methods were used for univariate and multivariate analyses for overall survival (OS) and progression-free survival (PFS). RESULTS A total of 136 patients were included, 29 without insurance at time of diagnosis and 107 with insurance. Of the patients without insurance, 6.9% were ≥60 years old at time of diagnosis compared to 45.8% of the patients with insurance (p=0.0001). Patients without insurance were also more likely to be Hispanic or Latino compared to patients with insurance (72.4% vs 10.3%, p= CONCLUSIONS In this study, we found no significant difference in OS between ALL patients based on insurance status. However, when controlling for other variables, lack of health insurance was associated with worse PFS. These results suggest that uninsured patients may be at a disadvantage in terms of their leukemia outcomes. Patients with health insurance may have fewer obstacles to timely, effective therapy, which decreases their chance of relapse. Our finding that Hispanic or Latino patients had better OS and PFS was surprising and may be explained by the generally younger age of these patients in our population. Further research is needed to investigate how lack of insurance specifically affects leukemia management and patient outcomes. Disclosures Bannerji: Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; AbbVie, Inc: Consultancy, travel support; Celgene: Consultancy; Pharmacyclics: Other: travel support; Pharmacyclics: Other: travel support; Gilead: Other: travel support; Gilead: Other: travel support; AbbVie, Inc: Consultancy; Merck: Other: travel support, Patents & Royalties: IP rights; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Celgene: Consultancy; Merck: Other: travel support, Patents & Royalties: IP rights.

Background REGN1979 is an anti-CD20 x anti-CD3 bispecific IgG4 antibody (Ab) modified to reduce Fc binding. Engaging both targets results in CD20-specific, local T-cell activation and cytotoxicity, a mechanism of action distinct from standard anti-CD20 Abs. Dose escalation is complete and a recommended Ph 2 dose has been determined. We report Ph 1 safety and efficacy results of REGN1979 in patients (pts) with R/R B-NHL previously treated with anti-CD20 Abs, including pts with progressive disease after anti-CD19 CAR T-cell (CAR T) therapy. Methods Primary objectives are to determine safety, tolerability, and occurrence of dose limiting toxicities (DLTs). Other objectives are to assess antitumor activity, pharmacokinetics (PK), and pharmacodynamics. Eligible pts with R/R B-NHL must have received prior CD20-directed therapy. Treatment consists of 12 weekly intravenous doses of REGN1979 followed by every 2-week dosing for 12 doses (36 weeks total). Results As of June 3, 2019, 96 pts (diffuse large cell B-cell lymphoma [DLBCL] [n=53], follicular lymphoma [FL] grade [Gr] 1-3a [n=25], mantle cell lymphoma [n=6], marginal zone lymphoma [n=6], or other [FL Gr 3b, FL unknown, FL ungraded, or Waldenström macroglobulinemia ] [n=6]) were treated with REGN1979 0.03-320 mg and received a median of 9 doses (range 1-24). Pts had a median of 3 prior lines of therapy (range 1-11); 12 pts with prior CAR T therapy were included in the safety analysis of which 6 were included in the efficacy analysis. Twenty-four pts remain on treatment; 18 completed treatment; 54 discontinued early (35 due to progressive disease [PD]). No pts with B-NHL experienced a DLT. The most common treatment-emergent adverse events (AEs) were pyrexia (n=74), CRS (n=55), chills (n=49), infections and infestations (n=47), fatigue (n=36), increased C-reactive protein (n=32), and anemia (n=32). Seven pts experienced Gr 3 CRS. The severity of CRS symptoms declined through optimized pre-medication even with REGN1979 dose escalation. Most common Gr 3 or 4 AEs were anemia (n=19), decreased lymphocytes/lymphopenia (n=19), infections and infestations (n=18), decreased neutrophils/neutropenia (n=17), and hypophosphatemia/decreased blood phosphorus (n=16). No pts had seizures or grade 4/5 neurologic AEs. Gr 3 neurologic AEs included depressed level of consciousness (unrelated), somnolence, and syncope (n=1 each). Neurological events were transient and none required permanent treatment termination. Five pts discontinued due to AEs: Gr 3 hemolysis; Gr 3 fatigue; Gr 2 and Gr 3 pneumonia; and Gr 3 neck abscess (1 each). Eleven pts died on study: PD (n=6), gastric perforation (n=1), cardiac arrest (n=1), lung infection (n=1), multi-organ failure (n=1), pneumonia (n=1). The Table and Figure show efficacy and duration of response for R/R DLBCL by dose level. Pts who had opportunity for response assessment at Week 12 were included in the analysis of response. Emerging data suggest increasing efficacy with higher doses in R/R DLBCL, with 5 of 8 pts treated at 80/160/320 mg achieving CR; at these doses 2 of 3 pts achieved CR after failure of CAR T therapy. Data also suggest increasing efficacy with increasing doses in R/R FL, but maximum efficacy appears to be achieved at lower doses than in DLBCL; in pts with FL Gr 1-3a treated at ≥5 mg, the ORR was 93% (13/14), and the CR rate was 71.4% (10/14). REGN1979 concentrations in serum increased linearly with dose during the first five weeks. Elevated levels of serum cytokines were observed, mostly in week 1, and no correlation was observed with clinical efficacy. Immunohistological analysis of malignant lymph node tissue demonstrated that pts with high and low CD20 expression achieved clinical response. Relapse among responders was seen with either maintenance or loss of CD20 expression, suggesting antigen-dependent and independent disease escape mechanisms. Conclusions/Summary Tolerability of REGN1979 has been demonstrated at doses up to the final dose level of 320 mg weekly, with no observed DLTs in pts with B-NHL. No pts discontinued due to neurologic AE. Activity was observed broadly in heavily pretreated R/R B-NHL pts treated with REGN1979. With increasing dose, more resistant tumors such as R/R DLBCL are showing benefit, even in pts with prior CAR T therapy failure. Based on these efficacy findings, a global Ph 2 study is underway to evaluate REGN1979 monotherapy in R/R FL Gr 1-3a, R/R DLBCL, and other R/R B-NHL subtypes. Disclosures Bannerji: AbbVie, Inc: Consultancy, travel support; Gilead: Other: travel support; Gilead: Other: travel support; Pharmacyclics: Other: travel support; Merck: Other: travel support, Patents & Royalties: IP rights; AbbVie, Inc: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy, Other: travel support, Research Funding; Celgene: Consultancy; Celgene: Consultancy; Merck: Other: travel support, Patents & Royalties: IP rights; Pharmacyclics: Other: travel support. Allan:Acerta Pharma: Consultancy; Sunesis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics LLC, an AbbVie company: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy; Verastem Oncology, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria. Arnason:Celgene/Juno: Consultancy; Regeneron Pharmaceuticals, Inc.: Consultancy. Brown:AstraZeneca: Consultancy; Acerta Pharma: Consultancy; Morphosys: Other: Data safety monitoring boards ; Sun Pharmaceuticals, Inc: Research Funding; Sun: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy; Teva: Honoraria; Sunesis: Consultancy; Pharmacyclics: Consultancy; Pfizer: Consultancy; Janssen: Honoraria; Invectys: Other: other; Loxo: Consultancy, Research Funding; Novartis: Consultancy; Octapharma: Consultancy; Kite: Consultancy, Research Funding; Dynamo Therapeutics: Consultancy; Catapult Therapeutics: Consultancy; BeiGene: Consultancy; Gilead: Consultancy, Research Funding; Genentech/Roche: Consultancy. Advani:Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Seattle Genetics: Consultancy, Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kura: Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity Pharma: Research Funding; Janssen: Research Funding; Merck: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cell Medica, Ltd: Consultancy; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agensys: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stanford University: Employment, Equity Ownership; Regeneron: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Seattle Genetics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Mayo Clinic Rochester: Employment. O'Brien:Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Acerta: Research Funding; Alexion: Consultancy; Amgen: Consultancy; Aptose Biosciences, Inc: Consultancy; Astellas: Consultancy; Celgene: Consultancy; Eisai: Consultancy; Gilead: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Kite: Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Regeneron: Research Funding; Verastem: Consultancy; Sunesis: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; TG Therapeutics: Consultancy, Research Funding. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Genentech: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Duell:Regeneron Pharmaceuticals, Inc.: Research Funding. Martin:I-MAB: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Sandoz: Consultancy; Teneobio: Consultancy. Charnas:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ambati:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Adriaens:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ufkin:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Zhu:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Li:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Gasparini:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ibrahim:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Jankovic:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Fiaschi:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Aina:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Zhang:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Deering:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Hamon:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Thurston:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Murphy:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Weinreich:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Yancopoulos:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Lowy:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Sternberg:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Topp:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: The data described in the abstract will report on use REGN1979 in a Phase 1 clinical trial of patients with B-NHL.

Background: The Bruton's tyrosine kinase inhibitor ibrutinib is highly effective as a monotherapy in relapsed/refractory mantle cell lymphoma (MCL) with an overall response rate of 68% (Wang et al, NEJM 2013), but the duration of response is shorter than what is seen in chronic lymphocytic leukemia, and the survival of patients who progress after receiving ibrutinib is as short as 3 months (Martin et al, Blood, 2016). In addition, the complete response (CR) rate is only 21%. Ibrutinib-containing combinations may improve depth and duration of response in patients with relapsed/refractory MCL. While use of the proteasome inhibitor, bortezomib, can be limited due to the development of peripheral neuropathy, it has an ORR of 33% (CR rate 8%) in MCL, and preclinical models suggest a synergism between proteasome inhibitors and ibrutinib in MCL cell lines (Axelrod et al, Leukemia 2014). We developed a phase 1/2 trial of ibrutinib combined with the oral proteasome inhibitor ixazomib in patients with relapsed/refractory MCL. Methods: PrE0404 will be open at 18 sites nationwide and is registered at clinicaltrials.gov (NCT03323151). It is currently enrolling patients with relapsed/refractory MCL who have received at least 1 prior line of combination therapy. Patients receiving prior BTK or proteasome inhibitors are eligible, and patients may have received prior autologous or allogeneic transplantation as long as they do not have active graft versus host disease. Patients must have ≤ grade 1 peripheral neuropathy. For phase 1, patients are required to have been off of a BTK inhibitor for 3 months. Starting dose of ibrutinib for all patients is 560mg daily, and dose levels of ixazomib for the phase 1 trial range from 3mg to 4mg days 1, 8, and 15 of a 28 day cycle. Patients continued therapy until disease progression or unacceptable toxicity. For the phase 1 portion of the study, patients are monitored for a dose limiting toxicity (DLT) during cycle 1, defined as grade 3 thrombocytopenia with significant bleeding, select grade 3 non-hematologic toxicities, grade 4 thrombocytopenia, grade 4 febrile neutropenia, grade 4 non-hematologic toxicity, or any grade 5 toxicity. In addition, any toxicity-related dose delay > 7 days of ibrutinib or ixazomib or an inability to receive all 3 doses of ixazomib during cycle 1 are considered DLT's. The maximum tolerated dose/recommended phase 2 dose will be the dose at which fewer than 1/6 patients experience a DLT, with the maximum dose of ixazomib will be 4mg. The primary endpoint for the phase 2 portion of the study is CR rate, and patients will be assigned to one of two cohorts based on prior BTK-inhibitor exposure. For ibrutinib-naïve patients, we will target a CR rate of 40% (based on a historical CR rate of 21% for ibrutinib), and for ibrutinib-pretreated patients, we will target a CR rate of 23% (based on a historical CR rate of 8% for bortezomib). There is 86% statistical power & a one-sided 10% alpha to test each hypothesis. We will accrue 31 patients to each cohort in order to detect this difference. Secondary and exploratory endpoints will include progression-free and overall survival, overall response, toxicity, frequency of BTK mutations, and response based on molecular risk stratification. As of July 2019 the study is open to accrual at 14 sites and is expected to move to phase 2 in fall 2019, at which time it will be expanded to 18 sites. Disclosures Cohen: Hutchison: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Astra Zeneca: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; UNUM: Research Funding; Gilead/Kite: Consultancy; Takeda Pharmaceuticals North America, Inc.: Research Funding. Portell:Infinity: Research Funding; Roche/Genentech: Research Funding; Xencor: Research Funding; TG Therapeutics: Research Funding; Acerta/AstraZeneca: Research Funding; Kite: Consultancy, Research Funding; Bayer: Consultancy; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; BeiGene: Consultancy, Research Funding. Hamadani:ADC Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Otsuka: Research Funding; Celgene: Consultancy; Merck: Research Funding; Medimmune: Consultancy, Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Landsburg:Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Triphase: Research Funding; Takeda: Research Funding; Takeda: Research Funding; Seattle Genetics: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau. Kahl:Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Consultancy; TG Therapeutics: Consultancy. OffLabel Disclosure: Ixazomib is not currently approved for mantle cell lymphoma.

Introduction Approximately 20% of patients (pts) with classical Hodgkin lymphoma (cHL) are age ≥ 60 years (yrs) at diagnosis (dx). Standard anthracycline-based therapies (ABTx) have historically shown lower efficacy and greater toxicity in this older population compared with younger pts, especially for unfit or frail pts. However, prior analyses have pre-dated the use of brentuximab vedotin (BV) and other novel targeted agents in the front-line setting and there remains no clearly defined or unified standard of care for this pt population. Studies in older lymphoma pts have also defined specific categories of pt fitness that may potentially guide therapy, although continued validation of these definitions in cHL are needed. We performed a large, multicenter retrospective study to identify current practice patterns in the US in older untreated cHL pts with specific attention to pt fitness using established definitions and to outcomes with ABTx versus non-ABTx. Methods Following IRB approval at each site, detailed pathologic and clinical data, including geriatric assessments (GAs) for the latter, were collected across 10 US academic medical centers. Eligible pts included: cHL dx on or after 1/1/2010, age ≥ 60 yrs at dx, and no preceding hematologic malignancy. Subjects with inadequate clinicopathologic and outcomes data or with dx other than cHL were excluded. A multivariable Cox proportional hazards model was developed to study the association of PFS and OS with various factors of interest, and survival rates were estimated by Kaplan-Meier using SPSS. Associations were considered significant for two-sided P values ≤ 0.05. Results Among 254 eligible older cHL pts with newly diagnosed disease, clinical features included: median age 67 yrs (range 60-90+), 54% male, 64% stage III/IV, 46% B symptoms, and 86.1% ECOG PS 0-1. 68.9% had nodular sclerosis, 18.9% mixed cellularity, and 12.2% other subtypes; EBV was detectable by IHC or peripheral blood in 39.3% of evaluable cases (n=98). In terms of geriatric measures, 31 pts (12.2%) had loss of at least one ADL; 40 (15.8%) had a geriatric syndrome; and 16 (6.3%) had both. Of note, only one pt underwent a comprehensive GA prior to treatment. Using established fitness definitions in lymphoma (Tucci et al, 2015), pts were classified as "Fit" (n=129; 50.8%), "Unfit" (n=8; 3.2%), or "Frail" (n=112 (44.1%); 5 (2%) were unclassifiable due to incomplete data (Table 1). Front-line regimens included ABVD (n=145; 57.1%), AVD (n=33; 13.0%), and CHOP (n=18; 7.1%). 6 pts (2.4%) received BV monotherapy; 21 (8.3%) received BV with AVD, the latter either concurrently (N=11) or sequentially (n=10). 11 pts did not receive systemic tx, of whom 9 received radiation alone; 58 pts received radiation with systemic tx. ABVD recipients received an average of 7.4 doses of bleomycin (range 1-14) and 18.4% (n=26) had pulmonary toxicity. In addition, 56.7% (n=130) of pts experienced at least one tx-related toxicity, which was similar across all fitness groups (Table 1). 15.1% (n=38) of pts stopped tx due to toxicity, which was noted more often in "frail" pts though it was relatively uncommon. 11 pts (4.3%) experienced treatment-related mortality (TRM). Compared with pts receiving non-ABTx, ABTx was associated with significantly improved PFS (HR 0.391, P=0.008) and OS (HR 0.195, P=0.0004). ECOG PS >1 was associated with inferior PFS (HR=1.96, P=0.017) and OS (HR=3.09, P=0.002). Pts defined as "frail" had no apparent difference in PFS compared with fit pts (Figure 1A;P=0.169), although decreased OS was seen (Figure 1B; P=0.01). Discussion To the best of our knowledge, these data represent one of the largest analyses of older cHL pts in the modern era. Our real-world analysis shows that in those who are able to receive them, anthracyclines provide meaningful survival benefit in this older cHL patient population and can be well-tolerated for many pts. The impact of dose intensity and backbone regimen are not yet known. In addition, current definitions of "fitness" incompletely identified pts at risk for poor outcomes or greater toxicity. Further studies are planned to better delineate fitness in this population. Disclosures Bartlett: Celgene: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Affimed: Research Funding; Merck: Research Funding; Janssen: Research Funding; Immune Design: Research Funding; Gilead: Research Funding; Millenium: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Research Funding; Forty Seven: Research Funding; Genenetech: Research Funding; Bristol-Myers Squibb: Research Funding. Grover:Seattle Genetics: Consultancy. Bennani:Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board. Hill:Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding. Advani:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Kura: Research Funding; Janssen: Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Regeneron: Research Funding; Infinity Pharma: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Agensys: Research Funding; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Cell Medica, Ltd: Consultancy; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Magarelli:Tevan Oncology: Speakers Bureau. Feldman:Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding. Cohen:Astra Zeneca: Research Funding; ASH: Research Funding; UNUM: Research Funding; Hutchison: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Lymphoma Research Foundation: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Janssen Pharmaceuticals: Consultancy; Genentech, Inc.: Consultancy, Research Funding. Evens:Seattle Genetics: Consultancy, Honoraria, Research Funding; Tesaro: Research Funding; Epizyme: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria. Portell:AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding.

The article presents the implementation and findings of a successful collaborative effort with the Oklahoma State Regents for Higher Education (OSRHE), Tulsa Community College (TCC), and two local public school districts, Tulsa Public Schools (TPS) and Union Public Schools (UPS). Known as EXCELerate, it's a five-semester dual enrollment pilot program that received state policy exceptions for juniors and seniors to enroll in dual enrollment courses and supportive resources from the participating agencies. Whereas the traditional dual enrollment student is White and college-going, the program's intent was to increase the number of high school students who may be first-generation, lower-socioeconomic, ethnic or non-ethnic. The article identifies three major barriers to successful dual enrollment and completion: state policy, financial issues, and transportation. It also examines how these barriers were eliminated through a collaborative effort. The results demonstrate that over 87% of the juniors and seniors...