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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.

IMPORTANCE: It remains unclear how the historical exclusion of women and racial and ethnic minority groups from medical training, and therefore the oncologic subspecialties, has contributed to rates of faculty diversity among oncology departments over time. Oncologic faculty diversity is an important initiative to help improve care and address health disparities for an increasingly diverse US population with cancer. OBJECTIVES: To report trends in academic faculty representation by sex and by race and ethnicity for radiation oncology (RO) and medical oncology (MO) departments and to describe comparisons with the general US population, medical students, RO and MO trainees, clinical department chairs, and faculty in other departments. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used data from the Association of American Medical Colleges to analyze trends by sex and by race and ethnicity among full-time US faculty in RO and MO departments from 1970 through 2019. Data were analyzed between October 2020 and April 2021. MAIN OUTCOMES AND MEASURES: Proportions of women and individuals from underrepresented in medicine (URM) racial and ethnic groups (Black, Hispanic, and Indigenous individuals) were calculated among RO and MO academic departments; trends were analyzed over 5 decades. These proportions were compared with cohorts already described. In addition, proportions of women and URM individuals were calculated by faculty rank among RO and MO departments. RESULTS: In 1970, there were 119 total faculty in RO (10 women [8.4%] and 2 URM [1.7%]) and 87 total faculty in MO (11 women [12.6%] and 7 URM [8.0%]). In 2019, there were 2115 total faculty in RO (615 women [29.1%] and 108 URM [5.1%]) and 819 total faculty in MO (312 women [38.1%] and 47 URM [5.7%]). Total faculty numbers increased over time in both RO and MO. Faculty representation of URM women proportionally increased by 0.1% per decade in both RO (95% CI, 0.005%-0.110%; P

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.

This Viewpoint describes the concept of race-conscious medicine in oncology.

Purpose: Bendamustine and rituximab (BR) has been established as a superior frontline therapy over R-CHOP in the treatment of follicular lymphoma (FL). Yttrium-90 Ibritumomab tiuxetan (90YIT) is an effective consolidation strategy after chemotherapy induction. This prospective, single-arm, multicenter, phase II trial evaluated the response rate, progression-free survival (PFS), and tolerability of BR followed by consolidation with 90YIT in patients with untreated FL. Patients and Methods: The study included grade 1 to 3a FL patients aged ≥18 years, chemotherapy-naïve, and requiring treatment for stage II–IV disease. Study treatment included an initial rituximab treatment, followed by four cycles of BR. Patients were eligible for consolidation with 90YIT, 6 to 12 weeks after BR, if they obtained at least a partial response after induction had adequate count recovery and bone marrow infiltration < 25%. Results: Thirty-nine patients were treated. Eighty-two percent had an intermediate or high-risk Follicular Lymphoma International Prognostic Index score, and 6 of 39 (15%) were grade 3a. The response rate was 94.8%, and the complete response(CR)/CR unconfirmed (CRu) rate was 77% in the intention-to-treat analysis. The conversion rate from PR to CR/Cru after 90YIT was 81%. After median follow-up of 45 months, the PFS was 0.71 (95% confidence interval, 0.57–0.89). Conclusions: This report demonstrates that four cycles of BR followed by consolidation with 90YIT achieve high response rates that are durable. In addition, consolidation with 90YIT results in a high conversion rate of PR to CR/CRu. A short course of BR followed by 90YIT is a safe and effective regimen for frontline treatment of FL.

Purpose: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. Experimental Design: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. Results: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. Conclusions: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

PURPOSE Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger. PATIENTS AND METHODS We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score–weighted (PSW) analysis were performed. RESULTS Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2). CONCLUSION In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

LBA7564 Background: Patients with r/r B-NHL have a dismal prognosis. DIAL (Dual Immunomodulation in Aggressive Lymphoma) was a multi-center randomized phase II study testing the efficacy of nivolumab (PD-1 inhibitor) plus varlilumab (CD27 agonist) in this population. Methods: Patients were randomized (1:1) to nivolumab (240 mg IV every 2 weeks for 4 months, 480 mg IV monthly thereafter; group 1) alone or combined with varlilumab (3 mg/kg IV monthly; group 2). Cross-over (group 1 to 2) was allowed for progression. Primary endpoint was overall response (ORR) per LYRIC criteria. A sample size of 48 patients per arm would provide 80% power to detect increase in ORR from 25% to 45% using a one-sided test (p = 0.15). Pre-specified interim analysis occurred after half of the patients completed first radiologic assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Exploratory endpoints included tumor genomic assessment and immune profiling of blood and tumor. Results: 53 patients were enrolled (27 in group 1; 26 in group 2). Interim analysis included 24 patients from each arm. Mean age was 65.2 years, 34 (70.8%) were male, and 36 (75%) received prior CAR-T cell therapy. Baseline characteristics were balanced between arms. Grade ≥ 3 AEs were observed in 8 (33.3%) and 7 (30.4%) of patients in groups 1 and 2, respectively. Common AEs (> 5%) of any grade included fatigue, lymphopenia, diarrhea, rash. There were no treatment-associated deaths. Toxicity profile was similar between arms. Table summarizes efficacy outcomes. ORR was achieved in 6 patients (12.5%), not statistically different between arms; 4 responses were complete. Seven patients crossed over (1 responded after crossing). Median OS (8.6 vs 7.3 months; p = 0.39) and PFS (2.7 vs 1.4 months; p = 0.06) were similar between arms. Subgroup analysis of patients with prior CAR-T cell therapy showed similar ORR (5/36; 14%), not statistically different between arms. Correlative analysis results will be presented at conference. The trial met futility criterion on interim analysis and enrollment ceased based on pre-specified stopping rule. Conclusions: Dual immunomodulatory therapy did not enhance anti-tumor activity in patients with aggressive B-NHL compared to nivolumab alone. Response rates were low and consistent with previous data using PD-1 inhibitors in this population. Prior therapy with CAR-T cell does not seem to sensitize patients to PD-1 blockade. Toxicity profile was acceptable and dual therapy did not increase the rate of AEs. Clinical trial information: NCT03038672. [Table: see text]

Background Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed and refractory (R/R) setting, but once discontinued due to progression or side effects, it is unclear how successful further therapies will be. Moreover, there is no data on optimal sequencing of these treatments with standard therapies and other novel agents. In a multicenter, retrospective analysis we investigated whether exposure to CBT could sensitize HL to subsequent therapy. Materials and methods Seventeen centers across the US and Canada retrospectively queried medical records for eligible patients. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment using the Lugano criteria. Secondary aims included progression free survival (PFS), duration of response (DOR), and overall survival (OS). Results Eighty-one patients were included. Seventy-two percent had stage 3-4 disease, and the population was heavily pretreated with a median of 4 therapies before CBT. Most patients (65%) discontinued CBT due to progression. The ORR to post-CBT therapy was 62%, with a median PFS of 6.3 months and median OS of 21 months. Post-CBT treatment regimens consisted of chemotherapy (44%), targeted agents (19%), immunotherapy (15%), transplant conditioning (14%), chemotherapy/targeted combination (7%), and clinical trials (1%). No significant difference in OS was found when stratified by post-CBT regimen. Conclusion In a heavily pretreated R/R HL population, CBT may sensitize patients to subsequent treatment, even after progression on CBT. Post-CBT regimen category did not impact OS. This may be a novel treatment strategy, which warrants further investigation in prospective clinical trials. Implications for practice Relapsed and refractory (R/R) Hodgkin lymphoma (HL) presents a clinical challenge, and better treatment strategies are greatly desired to prevent these patients from ultimately succumbing to their disease. The results of this multicenter analysis concur with a smaller, earlier report that checkpoint blockade therapy usage in R/R HL may sensitize patients their subsequent treatment. This approach may potentially be used to extend the number of options patients have or to bridge them to transplant. Prospective data is warranted prior to practice implementation. As more work is done in this area, we may also be able to optimize sequencing of CBT and novel agents in the treatment paradigm to minimize treatment-related toxicity and thus improve patient quality of life.

While combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) cures most patients with diffuse large B-cell lymphoma (DLBCL), those with high-risk international prognostic index disease have inferior survival. Enzastaurin as a potent inhibitor of PKC-β and PI3K/AKT pathway suppressor has been tested in many clinical trials including two key studies in DLBCL: Phase III maintenance study (Preventing Relapse in Lymphoma Using Daily Enzastaurin [PRELUDE]) and a first-line Phase II study (S028). DNA extracted from PRELUDE patients’ blood samples was retrospectively genotyped identifying a novel genetic biomarker, DGM1 that showed high correlation with response to enzastaurin. A similar finding observed in the S028 study suggested that addition of enzastaurin to R-CHOP may significantly improve outcomes as frontline therapy for high-risk DGM1 positive DLBCL patients. ENGINE is a global, multicenter, placebo-controlled and randomized study to compare the effect of R-CHOP/enzastaurin as frontline treatment in high-risk DLBCL patients. The primary end point for this study is overall survival in patients who are DGM1 positive. Clinical Trial Registration Identifier: NCT03263026

Introduction We examined patient characteristics, treatments and outcomes of transformed mycosis fungoides (tMF) patients from COMPLETE: a large, multicenter, prospective cohort study of peripheral T-cell lymphoma patients in the US. Methods Patients with tMF were enrolled in COMPLETE at the time of transformation. For this analysis, we identified tMF patients with completed baseline, treatment and follow-up records. Median survival was assessed using Kaplan-Meier methodology. Results Of the 499 patients enrolled in COMPLETE, 17 had tMF. Median age was 61; 53% were male, 9 had elevated lactate dehydrogenase (LDH) and 9 had lymph node involvement. About one-quarter of the patients were African American and 47% had CD30+ disease. Median time to transformation was 53 months. All patients received systemic therapy, with 19% receiving concomitant radiotherapy. Most patients (87%) received single agents, including liposomal doxorubicin, pralatrexate and gemcitabine. Eight patients (50%) had reported responses to therapy. Median survival was 18 months. One- and two-year survival rates were 56% and 44%, respectively. Conclusions tMF often express CD30 and present with lymph-node involvement. Responses have been seen with single agents, but survival remains poor. Novel treatment approaches are urgently needed to improve outcomes.

Limited information is available on the efficacy of front‐line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real‐world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty‐seven patients with creatinine clearance (CrCl) 6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression‐free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02‐1.10, P, Bendamustine and Rituximab was a relatively effective first‐line regimen in real‐world untreated CLL patients with reduced renal function or coexisting conditions without TP53 disruption.In a matched‐adjusted indirect comparison with a cohort of CLL patients treated upfront, ibrutinib provided longer PFS than bendamustine and rituximab in those with advanced stage.

BACKGROUND The impact of MYC proto-oncogene, basic helix-loop-helix (MYC) translocations (with or without additional rearrangements involving the B-cell lymphoma 2 [BCL2] or BCL6 genes) on the response to salvage therapy and survival in patients with diffuse large B-cell lymphoma (DLBCL) who experience primary treatment failure is not well defined. METHODS This was a multicenter, retrospective study of the impact of MYC, BCL2, and BCL6 rearrangements in patients with DLBCL who failed to achieve complete remission or relapsed within 6 months after they completed upfront chemoimmunotherapy. RESULTS The authors examined response to salvage therapy, receipt of hematopoietic cell transplantation (HCT), and survival outcomes in MYC-negative (n = 120), MYC-positive single hit (SH) (n = 20), and MYC-positive double hit/triple hit (DH/TH) (n = 35) cohorts. The overall response rate in these cohorts to first salvage therapy (51%, 50%, and 54%, respectively) and receipt of HCT (52%, 40%, and 43%, respectively) were comparable between the 3 cohorts. The 2-year overall survival rate was 29.9% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 9.9% in the MYC-positive DH/TH cohort (P < .001), and no difference was observed between the SH and DH/TH cohorts (P = .8). The higher risk of death for patients with MYC-positive SH DLBCL (hazard ratio, 1.70; 95% confidence interval, 0.98-2.96; P = .06) and those with MYC-positive DH/TH DLBCL (hazard ratio, 2.22; 95% confidence interval, 1.41-3.50; P = .001) persisted after adjusting for covariates. For patients who underwent autologous HCT, the 2-year overall survival rate was 55.4% in the MYC-negative cohort, 0% in the MYC-positive SH cohort, and 19.4% in the MYC-positive DH/TH cohort (P < .001). All 4 MYC-positive patients who underwent allogeneic HCT relapsed in

Background With increased understanding of the unique entities, subtype-specific approaches for peripheral T-cell lymphoma (PTCL) are emerging, and more precise diagnoses are becoming increasingly important. Patients and Methods We analyzed the approach to the histopathologic diagnosis of PTCL using data from the comprehensive oncology measures of peripheral T-cell lymphoma (COMPLETE) study. The COMPLETE trial is a large prospective cohort study of patients with newly diagnosed PTCL in the United States. Results A total of 499 patients were enrolled from 40 academic and 15 community-based centers. Baseline assessment forms were collected for 493 patients, of which 435 (88%) were available for analysis. The most common diagnoses were PTCL, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma, and angioimmunoblastic T-cell lymphoma (AITL). A mean of 10 markers (range, 0-21) was assessed per patient. CD30 was assessed frequently but not uniformly in cases that were not anaplastic large cell lymphoma. Only 17% of PTCL-NOS cases were assessed for PD1. CXCL13 was a relatively sensitive marker in AITL, expressed in 84% of tested cases; however, only 3% of PTCL-NOS cases were tested. T follicular helper cell marker assessment differed between academic and community practices, with PD1 more often evaluated by academic centers in cases of AITL (62% vs. 12%; P = .01). Conclusion The diagnostic workup for PTCL in the United States varies widely and often lacks important phenotypic information to fully characterize the lymphoma. Gaps in testing of selected markers should be filled, given the impending revision to the World Health Organization classification. The accuracy of diagnosis will become increasingly important as we enter the era of targeted treatment for PTCL.

BACKGROUND Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States. METHODS Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States. Patients with nodal PTCL and completed records regarding baseline characteristics and initial therapy were included in this analysis. All statistical tests were 2-sided. RESULTS Of a total of 499 patients enrolled, 256 (51.3%) had nodal PTCL and completed treatment records. As initial therapy, patients received doxorubicin-containing regimens (41.8%), regimens containing doxorubicin plus etoposide (20.9%), other etoposide regimens (15.8%), other single-agent or combination regimens (19.2%), and gemcitabine-containing regimens (2.1%). Survival was found to be statistically significantly longer for patients who received doxorubicin (log-rank P = .03). After controlling for disease histology and International Prognostic Index, results demonstrated a trend toward significance in mortality reduction in patients who received doxorubicin compared with those who did not (hazard ratio, 0.71; 95% confidence interval, 0.48-1.05 [P = .09]). CONCLUSIONS To the authors' knowledge, there is no clear standard of care in the treatment of patients with PTCL in the United States. Although efforts to improve frontline treatments are necessary, anthracyclines remain an important component of initial therapy for curative intent. Cancer 2017;123:1174–1183. © 2016 American Cancer Society.

Background The role of autologous stem cell transplantation (ASCT) in the first complete remission (CR1) of peripheral T-cell lymphomas (PTCLs) is not well defined. This study analyzed the impact of ASCT on the clinical outcomes of patients with newly diagnosed PTCL in CR1. Methods Patients with newly diagnosed, histologically confirmed, aggressive PTCL were prospectively enrolled into the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE) study, and those in CR1 were included in this analysis. Results Two hundred thirteen patients with PTCL achieved CR1, and 119 patients with nodal PTCL, defined as anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or PTCL not otherwise specified, were identified. Eighty-three patients did not undergo ASCT, whereas 36 underwent consolidative ASCT in CR1. At the median follow-up of 2.8 years, the median overall survival was not reached for the entire cohort of patients who underwent ASCT, whereas it was 57.6 months for those not receiving ASCT (P = .06). ASCT was associated with superior survival for patients with advanced-stage disease or intermediate-to-high International Prognostic Index scores. ASCT significantly improved overall and progression-free survival for patients with AITL but not for patients with other PTCL subtypes. In a multivariable analysis, ASCT was independently associated with improved survival (hazard ratio, 0.37; 95% confidence interval, 0.15-0.89). Conclusions This is the first large prospective cohort study directly comparing the survival outcomes of patients with nodal PTCL in CR1 with or without consolidative ASCT. ASCT may provide a benefit in specific clinical scenarios, but the broader applicability of this strategy should be determined in prospective, randomized trials. These results provide a platform for designing future studies of previously untreated PTCL.

8022 Background: The BTK inhibitor ibrutinib (IB) has advanced the treatment for patients (pts) with CLL, however, among pts with high-risk CLL, disease control with IB is less durable. Ublituximab (UTX) is a glycoengineered mAb with enhanced ADCC. The GENUINE study evaluated the addition of UTX to IB vs. IB alone in high-risk rel/ref CLL. With a median follow up now 3.5+ yrs, we present the final results. Methods: Eligible pts having rel/ref CLL with centrally confirmed del17p, del11q, and/or a TP53 mutation, were randomized 1:1 to IB (420 mg QD) alone or with UTX (900 mg on D1, 8, 15 of Cy 1, D1 of Cy 2-6, and Q3 Cy thereafter). No limit on # of prior Tx; prior IB excluded. Primary endpoint was overall response rate (ORR) by iwCLL 2008 (excludes PR-L); secondary endpoints were CR rate, peripheral blood MRD negativity (analyzed centrally), PFS, and safety. Response was by blinded independent review. Results: 117 pts were treated (59 in UTX + IB arm; 58 in IB arm). Med age was 66 yrs and med # of prior Tx was 1 (range 1-5) for each arm. Baseline features were relatively balanced including ECOG, gender, and med time since diagnosis (6+ yrs). 17p del was greater in the IB arm (50% vs 44%); bulky disease was greater in UTX + IB arm (47% vs 28%); IGHV-unmut was 83% for both arms. At data-cutoff of Sep 1, 2019, AEs were comparable between the arms, except infusion reactions (UTX + IB: All G 53% / G 3/4 3%) and neutropenia (All G 36% vs 21%, G 3/4 19% vs. 12%) which were higher for UTX + IB. At a med follow up of 42 mos, all efficacy endpoints were in favor of UTX + IB (see Table). Conclusions: In contrast to prior studies adding rituximab to IB, GENUINE is the first randomized trial to demonstrate a PFS benefit with the addition of an anti-CD20 to IB. Increasing depth of response (CR rate, MRD-neg) post first year of Tx supports maintenance therapy with UTX. Clinical trial information: NCT02301156 . [Table: see text]

8046 Background: Patients (pts) with relapsed iNHL have limited standard treatment options. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported 39.4-mo median PFS in R/R iNHL pts (AUGMENT; J Clin Oncol. 2019;37:1188). Methods: MAGNIFY is a multicenter, phase IIIb trial in pts with R/R FL gr1-3a, MZL, or MCL (NCT01996865) exploring optimal lenalidomide duration. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and then q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in pts with SD, PR, or CR to R2 vs rituximab maintenance for 18 mo. Data presented here focus on induction R2 in efficacy-evaluable FL and MZL pts (MCL not included) receiving ≥ 1 treatment with baseline/post-baseline assessments to analyze the primary end point of ORR by 1999 IWG criteria. Results: As of June 16, 2019, 393 pts (81% FL gr1-3a; 19% MZL) were enrolled with a median follow up of 23.7 mo (range, 0.6-57.8) for censored pts (n = 335). Median age was 66 y (range, 35-91), 83% had stage III/IV disease, with a median of 2 prior therapies (95% prior rituximab-containing). ORR was 69% with 40% CR/CRu (Table). Median DOR was 39.0 mo, and median PFS was 40.1 mo. 199 pts (51%) have completed 12c of R2, and 188 (48%) have been randomized and entered maintenance. 139 pts (35%) prematurely discontinued both lenalidomide and rituximab, primarily due to AEs (n = 52, 13%) or PD (n = 45, 11%). Most common all-grade AEs were 48% fatigue, 43% neutropenia, 36% diarrhea, 31% nausea, and 30% constipation. Grade 3/4 AE neutropenia was 36% (9 pts [2%] had febrile neutropenia); all other grade 3/4 AEs occurred in < 7% of pts. Conclusions: R2 is active with a tolerable safety profile in pts with R/R FL and MZL, including rituximab-refractory, double-refractory, and early relapse pts. Clinical trial information: NCT01996865 . [Table: see text]

Follicular lymphoma (FL) patients treated with firstline R‐CHOP who experience progression of disease (POD) within 2 years have a shorter survival than those who do not have POD within 2 years. Whether this observation holds for patients treated initially with biologic immunotherapy alone is unknown. We performed a retrospective analysis of 174 patients pooled from three frontline rituximab (R)‐based nonchemotherapy doublet trials: R‐galiximab (Anti‐CD80, CALGB 50402), R‐epratuzumab (Anti‐CD22, CALGB 50701), and R‐lenalidomide (CALGB 50803) to determine outcomes of early progressors and risk factors for early POD, defined as progression within 24 months from study entry. Twenty‐eight percent (48/174) of patients had early POD. After adjusting for the Follicular Lymphoma International Prognostic Index (FLIPI), patients with early POD from study entry had a worse OS compared with patients who did not progress within 2 years (HR = 4.33 (95% CI 1.50‐12.5), P = 0.007). For early POD, the 2‐year survival was 80% vs 99% for nonearly POD, and the 5‐year survival was 74% vs 90%, respectively. These findings suggest that the adverse survival of patients with early POD may be independent of initial treatment modality.

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.

Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States.Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States. Patients with nodal PTCL and completed records regarding baseline characteristics and initial therapy were included in this analysis. All statistical tests were 2-sided.Of a total of 499 patients enrolled, 256 (51.3%) had nodal PTCL and completed treatment records. As initial therapy, patients received doxorubicin-containing regimens (41.8%), regimens containing doxorubicin plus etoposide (20.9%), other etoposide regimens (15.8%), other single-agent or combination regimens (19.2%), and gemcitabine-containing regimens (2.1%). Survival was found to be statistically significantly longer for patients who received doxorubicin (log-rank P = .03). After controlling for disease histology and International Prognostic Index, results demonstrated a trend toward significance in mortality reduction in patients who received doxorubicin compared with those who did not (hazard ratio, 0.71; 95% confidence interval, 0.48-1.05 [P = .09]).To the authors' knowledge, there is no clear standard of care in the treatment of patients with PTCL in the United States. Although efforts to improve frontline treatments are necessary, anthracyclines remain an important component of initial therapy for curative intent. Cancer 2017;123:1174-1183. © 2016 American Cancer Society.

Introduction: FASN catalyzes de novo fatty acid (FA) biosynthesis, which is an oncogenic function observed in many cancers, including NHL. HIF1a inducible FASN activity is responsible for overcoming negative hypoxic influence and upregulation of glucose metabolism as observed during premalignant transformation. FASN catalytic activity is also dependent on precursors derived from glucose metabolism. However, implications of FASN targeted therapies on these interdependent metabolic interactions and the overall impact on cancer cell proliferation remains unknown. Methods: FASN small molecule inhibitors cerulenin, orlistat, TVB3657 and TVB3166 were evaluated using a diverse panel of B cell NHL lines and primary NHL cells for the impact on FASN inhibition signaling & induction of cell death (MTT, caspases & AnnexinV/PI). Global transcriptomics were done with Affymetrix Human 2.0 ST Genechip with Gene Set Enrichment and Ingenuity Pathway Analysis (GSEA & IPA). Metabolomic profiling was performed using mass spectrometry. TXNRD1, GSR, NQO1 expression and activity were evaluated by western blot and using enzyme assay kits. Global DNA & RNA synthesis were evaluated using ClickIt Edu and EU assay kits. RNAseq data available from 775 NHL patients were utilized for metabolic transcriptome mapping. Results: Treatment with all FASN inhibitors resulted in dose- and time-dependent reduction (>90%) in cell viability and cell death in all NHL cell lines. GSEA and IPA identified cell cycle & RNA metabolism as downregulated biological processes with carbohydrate and oxidative stress as upregulated biological processes observed. "Key gene" analysis predicted TNF signaling as a prominent response to FASN inhibition, validated as increased TNF secretion by ELISA with cell fractionation and western blot analysis revealing activation of TNF-PI3K signaling. Activation of PI3K with FASN inhibition also corresponded with increased expression of PI3K-dependent metabolic genes associated with glucose and lipid metabolism. Furthermore, metabolomic profiling in SUDHL10 cells revealed accumulation of the FASN precursor acetyl-CoA with FASN inhibition that was accompanied by increased ketogenic glycolytic and citric acid cycle activity. In addition, NADPH accumulation (FASN substrate) occurred with FASN inhibition, which was accompanied with reduction in ribose-phosphate and nucleotide pools as these processes are relevant to NADPH-generating PPP function. G6PD, TXNRD1, GSR & NQO1 were identified as "key genes" responsive to FASN inhibition. Interestingly, this cluster of "key genes" represented the entire enzymatic activity related to the first rate-limiting step in PPP. Subsequently, we determined that increased NADP(H) pools were responsible for impaired NADPH regenerating functions of TXNRD1 and GSR antioxidant enzymes, with PI3K-dependent activation of NQO1 and uptake of glucose facilitating de novo glutathione synthesis, which substituted for the loss of antioxidant functions in SUDHL10, SUDHL4 and Raji cells. All responses were sensitive to inhibition by PI3K inhibition (e.g., BKM120) with co-targeting via FASN & PI3K inhibition resulting in markedly increased oxidative stress, loss of mitochondrial membrane potential & synergistic cell death in NHL cell lines and primary NHL cells. Finally, FASN inhibition was associated with reduction in ribo/deoxy-ribonucleotide pools that decreased global transcriptional activity (de novo RNA synthesis, by EU labeling) and replication (by EdU incorporation in DNA) (Fig 1). Analysis of RNAseq data and mapping of metabolic transcriptome from 772 NHL patients showed consistently elevated expression of genes related to glycolysis, citric acid cycle, fatty acid and nucleotide metabolism in patients with mutations in p53, MYC, BCL2, mTOR, MYD88, PIM2 & CREBP genes, suggesting that these onco-metabolic interactions may be important for lymphomagenesis. Conclusions: Taken together, FASN oncogenic activity appears to extend beyond de novo fatty acid biosynthesis, serving as a central onco-metabolic regulator of malignant cell proliferation vis-à-vis integrating glucose, nucleotides, and antioxidant metabolic functions in NHL. In addition, co-targeting FASN and PI3K induced synergistic cell death. Altogether, blocking FASN and the dependent onco-metabolic functions represent highly novel targets for therapeutic strategies in NHL. Disclosures Chen: Oncomics, LLC: Consultancy, Patents & Royalties. Dave:Data Driven Bioscience: Equity Ownership. Evens:Seattle Genetics: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Tesaro: Research Funding; Verastem: Consultancy, Honoraria.

7513 Background: Standard treatment is lacking for patients with relapsed indolent NHL (iNHL). PI3K inhibitors reported a median PFS of < 1 y in R/R iNHL. The immunomodulatory agent lenalidomide shows enhanced activity with rituximab (ie, R2), which recently reported a 39.4-mo median PFS in R/R iNHL patients (AUGMENT; Leonard. ASH 2018:445). Methods: MAGNIFY is a multicenter, non-registrational phase IIIb trial in patients with R/R FL grade 1-3a and MZL designed to determine the optimal duration of lenalidomide. Lenalidomide 20 mg/d, d1-21/28 + rituximab 375 mg/m2/wk c1 and q8wk c3+ (R2) are given for 12c followed by 1:1 randomization in patients with stable disease or better to continued R2 vs rituximab maintenance. These analyses evaluate the primary endpoint of ORR by 1999 IWG criteria for induction R2 in efficacy-evaluable patients receiving ≥ 1 treatment with baseline/post-baseline assessments. Results: At a median 16.7 mo follow-up, 370 patients (80% FL grade 1-3a; 20% MZL) were enrolled with a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab-containing). Efficacy-evaluable patients showed a 73% ORR and 45% CR (Table). Median TTR was 2.7 mo, median DOR was 36.8 mo, and median PFS was 36.0 mo. 142 of 370 patients have been randomized and entered maintenance. The most common all-grade AEs were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Grade 3/4 AE neutropenia was 34%; all other grade 3/4 AEs were < 6%. Conclusions: R2 therapy is active with a tolerable safety profile in patients with R/R FL and MZL, and in patients refractory to rituximab. Clinical trial information: NCT01996865. [Table: see text]

Introduction Case 1 The patient is a 75-year-old, otherwise healthy male who had a history of developing a bilateral axillary ‘burning,’ with a painful, pruritic erythematous rash in bilateral axillae, right worse than left. The rash persisted for 2 months despite topical steroid treatment. Physical exam revealed an 8 4 cm pink tumor with erosion in the ight axilla. Biopsy of the right axillary tumor revealed mycosis funoides (MF) with large cell transformation (Figure 1A). There was a onfluent dermal mass of enlarged and atypical lymphocytes, with xocytosis of lymphocytes into the overlying atrophic epidermis. The arge lymphocytes contained vesicular chromatin and variably promnent nucleoli, representing 75% of the infiltrating lymphocyte poplation. Also present was a minor population of intermixed small ymphocytes with complexly folded nuclei and condensed nuclear hromatin. The large atypical lymphocytes were positive for CD3, D4, and CD30, and negative for CD8, anaplastic lymphoma ki

7504 Background: Patients (pts) with high-risk chronic lymphocytic leukemia (CLL) defined by interruptions in TP53 (either by mutation or deletion) or loss of chromosome 11q experience inferior outcomes with ibrutinib (IB) monotherapy (O’Brien ASH 2016). Ublituximab (UTX) is a novel glycoengineered mAb with enhanced ADCC targeting a unique epitope on the CD20 antigen. GENUINE is the first randomized Ph 3 trial conducted assessing the addition of a novel agent to ibrutinib in high-risk rel/ref CLL, and evaluates IB monotherapy vs. UTX + IB. Methods: Eligible pts with rel/ref CLL and centrally confirmed del17p, del11q, and/or a TP53 mutation were randomized 1:1 to receive IB (420 mg QD) alone or with UTX (900 mg on D1, 8, 15 of Cycle 1, D1 of Cycle 2-6, and Q3 Cycles thereafter). There was no limit on number of prior therapies. Prior IB exposure was excluded. The primary endpoint was overall response rate (ORR) per iwCLL 2008 criteria, with secondary endpoints including CR rate, MRD negativity, PFS, time to response (TTR) and safety. Results: 126 pts were randomized at sites in the US and Israel, with 117 pts treated (59 on UTX + IB, 58 on IB alone). Median age 67, median 3 prior therapies (range 1-8), > 70% of were male. High-risk cytogenetics were relatively balanced with ~ 50% of pts having del17p. UTX+IB was well tolerated, with infusion reactions the most prevalent AE (44%, GR3/4 5%). Neutropenia was comparable with the combination (17%, Gr3/4 7% vs. 10%, Gr3/4 9%), and other AE’s were similar or lower with UTX+IB vs. IB alone (all grades), including fatigue (17% vs. 31%), dizziness (12% vs. 21%), contusion (12% vs. 26%), anemia (10% vs. 16%), and myalgia (9% vs. 14%). At median follow-up of 12 mo, best ORR per independent central review was 80% for UTX + IB vs. 47% for IB alone (p < 0.001). While not powered for secondary endpoints, observed advantages were seen in PFS and radiographic CR rate in the UTX + IB arm. CR and MRD confirmation is ongoing. Median TTR for the combo was 1.97 mo vs. 3.8 mo for IB alone. Both arms have responses pending confirmatory assessments. Conclusions: The addition of UTX to IB demonstrated a superior response rate compared to IB alone without additional clinically significant toxicity. Clinical trial information: NCT02301156.

107 Background: Patients often require critical management during chemotherapy and may need constant monitoring during and post-treatment in an inpatient (IP) unit. However, many patients can receive safe and effective administration of chemotherapy in an outpatient (OP) infusion setting, which respects patient’s wishes to shorten hospitalization stays. Optimizing OP treatment can also result in better utilization of resources that require critical monitoring. Since IP chemotherapy is not reimbursed separately, it is often considered a financial loss. This study evaluated the opportunity to decrease length of stay (LOS), reduce costs for our hematology/oncology inpatient practice, and increase utilization of a new infusion suite adjacent to IP unit. Methods: Work followed a Lean Six Sigma methodology – Define, Measure, Analyze, Improve, and Control. Multi-disciplinary clinical teams worked with quality improvement subject matter experts to explore regimens associated with inpatient administration of high-cost medications. Rituximab-based regimens were identified as the greatest opportunity to optimize cost reduction in the IP unit. The team set a goal to deliver rituximab as an OP in the infusion suite following hospital discharge. Baseline utilization of rituximab in the IP unit, revenue of the new infusion suite, and mean LOS for patients receiving R-EPOCH, a rituximab based regimen, were determined. Results: Percentage of IP rituximab administration was reduced by 56% resulting in $355,506 of cost avoidance in the IP unit. Mean quarterly revenue in the OP infusion suite increased from $104,363 at baseline to $293,607 through the first nine months by shifting rituximab to the OP setting, which projects to an annualized improvement of $756,976. Median LOS for patients receiving R-EPOCH was reduced by 12 hours (p < 0.001). Conclusions: Our intervention has resulted in decreased administration of high-cost chemotherapy in the IP unit, reduced LOS, and increased patient convenience. In addition, the significant revenue generated in the OP infusion suite will support improving patient services at our not-for-profit medical center.

6577Background: Differences in outcomes have been reported in CLL pts receiving chemo±immunotherapy with non-Caucasians and males having inferior outcomes. Less is known if such disparities exist f...

7530Background: Although KI therapies are generally well-tolerated, intolerance is the most common reason for discontinuation, thus representing an unmet medical need. Umbralisib (TGR-1202), a next...

e18839Background: Social media (SM) has changed how patients and caregivers experience cancer. This quality improvement project aims to evaluate and understand the SM experience in a rural northern...

11009Background: To meet the rising demand for cancer care in low-middle-income countries (LMIC’s), an accredited Global Health track in Hematology-Oncology Fellowship programs (HOFP) is needed. To...

7516Background: In the relapsed/refractory (R/R) setting for indolent non-Hodgkin lymphoma (iNHL), duration of response (DOR) to and types of prior therapy are important factors in predicting outco...

Frederick Lansigan1, Diane M Stearns1, Francine Foss21Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA; 2Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USAAbstract: Denileukin diftitox (Ontak®) is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL), a rare lymphoproliferative disorder of the skin. Denileukin diftitox was the first fusion protein toxin approved for the treatment of a human disease. This fusion protein toxin combines the IL2 protein with diphtheria toxin, and targets the CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal agent to CD-25 bearing T-cells. Historically, immunotherapy targeting malignant T-cells including monoclonal antibodies has been largely ineffective as cytocidal agents compared to immunotherapy directed against B-cells such as rituximab. This review will summarize the development of denileukin diftitox, its proposed mechanism of action, the pivotal clinical trials that led to its FDA approval, the improvements in quality of life, and the common toxicities experienced during the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma requiring the sequential use of treatments such as retinoids, traditional chemotherapy, or biological response modifiers. The incorporation of the immunotoxin denileukin diftitox into the sequential or combinatorial treatment of CTCL will also be addressed.Keywords: denileukin diftitox, cutaneous T-cell lymphoma, fusion protein toxin

Acute leukemia is known to confer an elevated risk of both hemorrhagic and thrombotic complications, but the development of stroke in this population is poorly characterized. This study assesses clinical and epidemiologic factors in a population of inpatients with acute myeloid leukemia (AML) and stroke.Using the 2012 National Inpatient Sample, demographic and clinical data including age, gender, race, length of stay, in-hospital procedures, discharge diagnosis, disposition, and mortality incidence were extracted.Of 7,296,968 admissions, 10,984 patients with active AML were analyzed. Of these, 65 patients had a concomitant cerebrovascular accident (CVA) (hemorrhagic or ischemic). There was a 50-fold increase in the risk of stroke in patients with active AML compared with all admissions. Patients with AML and CVAs were found to have significantly higher inpatient mortality than for all admitted patients with stroke (36.9% vs. 6.7%; odds ratio, 5.5; 95% confidence interval, 2.3-8.8; P .0001). Multivariate logistic regression, after controlling for confounding variables, identified acute renal failure with tubular necrosis, hypernatremia, urinary tract infection, and secondary thrombocytopenia as significant predictors of stroke.Patients with AML have an elevated risk of CVA compared with all inpatients, and mortality in this population is high. Better characterization of risk factors of stroke in this vulnerable population is still needed.

Introduction During induction daunorubicin intensification from 45 mg/m2/day to 90 mg/m2/day has shown improved response and survival rates in AML patients. We retrospectively reviewed outcomes of daunorubicin 60 mg/m2/day (DNR60) versus daunorubicin 90 mg/m2/day (DNR90) in adult AML patients. Material and methods Newly diagnosed AML patients ≥18 years who received 7 + 3 with or without etoposide as frontline therapy from 1/1/2006 to 5/1/2013 were identified. Chi-square and Wilcoxon rank sum tests were used to compare characteristics. Kaplan–Meier curves were estimated for overall survival (OS). Univariate and multivariate Cox proportional hazard regression models were developed to determine independent predictors for survival. Results A total of 128 patients were included (DNR90 = 48 patients, DNR60 = 80 patients). The estimated 3-year OS rate in the DNR90 group was 56% (95% CI 38–70%), while in the DNR60 group was 34% (95% CI 23–44%). Multivariate analysis (MVA) in non-allotransplanted patients showed that unfavorable cytogenetics and worse performance status were associated with decreased OS while DNR intensification, etoposide use and site were associated with improved OS. In MVA of allotransplanted patients re-induction based on day-14 marrow was associated with worse OS. Conclusions Based on our retrospective study, initial DNR based induction chemotherapy intensification improved OS in non-allotransplanted patients. Prospective studies are needed to confirm this preliminary finding.

7541 Background: Translocations involving MYC are a hallmark of poor prognosis among patients with newly diagnosed DLBCL. The impact of MYC translocations with or without additional “hits” involving BCL2 or BCL6 in response to salvage therapy and survival in R/R DLCBL is not well defined. Methods: We performed a multicenter retrospective study of 176 patients with R/R DLBCL failing to achieve CR or relapsing within 6 months after completion of upfront chemoimmunotherapy and for whom FISH information on MYC, BCL2 and BCL6 was available. The objectives were to examine the response to salvage therapy, utilization of hematopoietic cell transplantation (HCT) and survival outcomes in MYC- (n = 120), MYC+ single hit (SH, n = 28), and MYC+ double hit (DH, n = 36) R/R DLBCL. Results: Overall response rate to first salvage therapy and utilization of HCT was comparable between the 3 cohorts (Table). 2-year OS was 0% in MYC+ SH, 8.8% in MYC+ DH and 29.9% in MYC- cases (p = 0.001) without difference in OS between SH and DH (P = 0.8). The higher risk of death for MYC+ SH (HR 1.79, 95% C.I. 1.03-3.11, P = 0.03) and MYC+ DH (HR 1.93, 95% C.I. 1.23-3.00, P = 0.004) persisted after adjustment for covariates. For patients who underwent auto-HCT, 2-year OS was 0% in MYC+ SH, 29.3% in MYC+ DH and 55.4% in MYC- cases (p < 0.001) without significant difference between SH and DH (P = 0.8). All 4 MYC+patients who underwent allo-HCT relapsed in < 4 months. Conclusions: MYC+ R/R DLBCL have similar response to salvage therapy than the MYC- counterparts but dismal survival irrespective of additional “hits” and even if HCT can be performed. MYC+ R/R DLBCL represents an unmet medical need and should be prioritized for clinical trials with novel agents and innovative cellular therapies. [Table: see text]

7502 Background: Chemoresistant patients with FL and those who progress within 2 y after initial diagnosis have poor outcomes (Casulo. JCO. 2015) and highlight an unmet need. Methods: MAGNIFY (NCT01996865) is a phase IIIb, multicenter, open-label study of relapsed/refractory (R/R) NHL patients, including grades 1-3b or transformed FL (tFL). Patients receive 12 cycles of lenalidomide plus rituximab (R2); those with stable disease or better are randomized 1:1 to maintenance R2 or rituximab alone. The primary endpoint is progression-free survival (PFS). This analysis focuses on FL: double-refractory (DR) patients are refractory to both rituximab (as monotherapy or combination) and an alkylating agent, and early relapse (ER) patients progressed or relapsed within 2 y of initial diagnosis. Results: As of July 19, 2016, the R/R FL population (N = 117) included 32 (27%) DR and 43 (37%) ER patients, median ages of 64 and 65 y, respectively, mostly grade 1-3a FL (94%; 91%) and 2 tFL (1 DR; 1 ER); 72% and 49% were stage IV at study entry. Patients had a median of 2 prior regimens (DR 3; ER 2). Of ER patients, 31 had first-line R-chemo vs 12 with R-mono/other. Response rates are in Table 1. Median time to response was 2.8 mo for DR and 2.7 mo for ER patients, with median duration not reached. 1-y PFS for FL patients was 66% (DR 66%; ER 45%); 1-y PFS for ER patients with first-line R-chemo was 50% vs 27% in others. Common grade ≥3 treatment-emergent AEs for DR and ER patients were neutropenia (53%; 33%), leukopenia (9%; 12%), and lymphopenia (9%; 5%). Conclusions: R2 followed by maintenance showed favorable activity and tolerable safety profiles in FL patients who are double-refractory or had early relapse ( < 2 years) after initial diagnosis. Enrollment in MAGNIFY is ongoing. Clinical trial information: NCT01996865. [Table: see text]

e18086 Background: Despite the rising burden of cancer, opportunities for global health education (GHE) at the fellowship level are lacking in hematology and oncology (HO). The Geisel School of Medicine at Dartmouth (GSMD) is pioneering a supervised one-month elective in Rwanda for HO fellows enrolled in U.S. programs. The goals are to expose fellows to a wider spectrum of disease states, improve clinical acumen, cultural sensitivity, and learn about health delivery in low-resource countries, while providing educational support for the local staff in a multidirectional learning paradigm. Methods: In partnership with the Rwandan Ministry of Health (MOH) and Partners in Health (PIH), GSMD created a one month elective rotation at the Butaro Cancer Center of Excellence (BCCOE) in Rwanda. HO Fellows with an interest in GHE apply to work in the outpatient clinic and inpatient wards in at BCCOE under direct supervision by GSMD faculty to provide input on cancer management including diagnosis, treatment, and chemotherapy administration. Fellows and attendings give lectures to hospital faculty and staff on topics requested by the leadership of BCCOE and participate in weekly telemedicine tumor boards. Fellows are evaluated using ACGME clinical competencies. Feedback from the Rwandan staff is obtained through customized evaluations. Results: The HO fellow gained exposure to advanced cancers including HIV-related malignancies, rare sarcomas and gestational trophoblastic disease, adhered to locally developed staging and treatment pathways, and gained confidence in guiding medical decisions. Fellows and faculty gave didactic presentations and provided bedside teaching. The local MOH and PIH staff gained new insight about approaches to management of complex disease states. This program promoted a multidirectional exchange of ideas related to patient care, disease states, and collaborative research projects. Conclusions: The institution of a global health fellowship elective in oncology has measurable benefits to HO fellows, cancer care providers in Rwanda and American faculty sub-specialists. This novel educational program will help to bridge the gap in global health disparities in a multifaceted approach.

e18227 Background: Streptococcus pneumoniae remains a leading cause of serious illness, including bacteremia, meningitis, and pneumonia among adults in the United States. Approximately 10% of all patients with invasive pneumococcal disease die of their illness, but case-fatality rates are higher for immunocompromised adults including cancer patients. Current Center for Disease Control (CDC) guidelines recommend routine use of 13-valent (Prevnar 13) and 23-valent (Pneumovax 23) pneumococcal vaccines (PV) for immunocompromised patients. We conducted a quality improvement (QI) project utilizing our electronic medical record (EMR) system to improve PV compliance (PVC) rates in our patients. Methods: We created automatic reminders called best practice alerts (BPA) and linked them to a smart order set within our EMR that appeared upon opening patient charts. The smart set ordered the correct vaccine in sequence based on CDC guidelines. From August 2015- January 2017, we implemented this BPA for one of six hematology providers and the remaining providers were provided with verbal guidelines and reminders to administer PV to their patients. Results: At baseline only 22% of 3000 hematology patients within the practice had received PV. The pilot provider with the BPA linked to a smart order set within the EMR improved PVC within his patients from 23% to 66%. Providers who were just given verbal guidelines improved PVC from an average of 22% to 45%. The difference in the improvement between the pilot provider and the reference group is 21% (p < 0.001). Conclusions: In an EMR era, we took advantage of the tools within our system to improve PVC rates. BPA linked to a smart order set within the EMR provided better means of improving PVC than verbal prompts in high-risk immunocompromised patients. Additionally, the increase in PVC throughout the hematology practice is due to primary care providers using similar reminders within the same EMR. The PV BPA will be conducted as a standard of care in our clinic and will be expanded to oncology patients as well.