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Background There is an unmet need for antithrombotic treatments for venous thromboembolic disease that do not increase bleeding risk. Selectins are cell adhesion molecules that augment thrombosis by activating immune cells to initiate the coagulation cascade. GMI‐1271, a potent small‐molecule E‐selectin antagonist, has been shown in mouse models to decrease thrombus burden with a low risk of bleeding. Methods A first‐in‐human study of GMI‐1271 was conducted to assess its safety, tolerability, and pharmacokinetic (PK) profile. As a secondary end point, biomarkers of coagulation, cell adhesion, and leukocyte/platelet activation were evaluated. Aims 1 and 2 were performed in healthy volunteers and evaluated single and multiple doses of the study drug, respectively. Aim 3 included 2 patients with isolated calf‐level deep vein thrombosis (DVT). Results GMI‐1271 showed consistent PK parameters for doses ranging from 2 to 40 mg/kg. Plasma levels increased in a linear manner with respect to dose, while clearance, volume of distribution, and half‐life were not dose dependent. No accumulation was seen with multiple consecutive doses. No serious adverse events (grade 3 or 4) were reported. Biomarker analysis demonstrated a trend in reduction of soluble E‐selectin (sEsel) levels with GMI‐1271 exposure, while exposure did not impact laboratory testing of coagulation. Two patients with calf vein DVT were treated with GMI‐1271 and demonstrated rapid improvement of symptoms after 48 hours, with repeat ultrasound showing signs of clot resolution. Conclusions We demonstrate that GMI‐1271 is safe in healthy volunteers and provide proof of concept that an E‐selectin antagonist is a potential therapeutic approach to treat venous thrombosis.

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.

Mantle cell lymphoma (MCL) is an incurable intermediate-grade lymphoma representing 5-6% of non-Hodgkin's lymphomas diagnosed in the United States. The introduction of inhibitors of Bruton's tyrosine kinase (BTK) into targeted therapy for MCL has significantly improved outcomes in patients with relapsed/refractory (R/R) disease. Since the initial approval of the first-generation inhibitor, ibrutinib, several second-generation inhibitors have been explored. Acalabrutinib, a second-generation BTK inhibitor, has demonstrated impressive efficacy in clinical trials along with a safety profile that thus far appears improved compared to ibrutinib. The results of a Phase II trial in patients with R/R MCL led to the approval of acalabrutinib in this patient population while fueling further exploration of acalabrutinib in several ongoing clinical trials.

Successful treatment of relapsed/refractory and rare subtypes of lymphomas remains a therapeutic challenge. Though the use of tumor profiling is increasing, little is described about how providers ultimately utilize this information in clinical decision-making. We reviewed 92 adult lymphoma patients who underwent an IRB-approved tumor sequencing protocol at the University of Michigan, MI-ONCOSEQ. Of this cohort, 60 had a targeted treatment suggested by their test results, and 11 patients ultimately underwent the MI-ONCOSEQ recommended therapy. One obtained complete response based on precision treatment recommendations. The two main barriers for targeted treatment utilization included inopportune timing (the patient either was sequenced too early or too late in their disease course) and clinical trial availability. While this study demonstrates the success of sequencing lymphomas for the identification of novel therapies, it also underlines the clinical challenges, namely the optimal timing and availability of trials, inherent in the successful application of this technology.

Background: All-trans retinoic acid (ATRA) serves as the backbone of the management of patients with acute promyelocytic leukemia (APL), with guidelines recommending the initiation of ATRA as soon as APL is suspected. As a regional referral center for patients with acute leukemia, those who are suspected of having APL are often transferred to our facility. However, many referring centers are unable to initiate treatment using ATRA. We conducted an exploratory analysis of the clinical availability of ATRA and the factors limiting access to this critical drug. Patients and Methods: The United States was divided into 6 geographic regions: Northwest, Southwest, Central, Southeast, Northeast, and the Great Lakes. Twenty hospitals were randomly selected from states within each of these regions and were surveyed as to whether they typically treated patients with acute leukemia, the availability of ATRA at their institution, and reported reasons for not stocking ATRA (if not available). Results: Less than one-third of hospitals queried (31%) had ATRA in stock. Neither the size of the hospital nor the hospital’s status as academic versus nonacademic (53% vs 31%; P=.08) influenced ATRA availability. Of the hospitals that referred patients with APL, only 14% (7/49) had ATRA readily available. Hospitals that treated patients with APL were more likely to have ATRA available than referring centers (58% vs 14%; P=.000002). Conclusions: Nearly two-thirds of the hospitals surveyed that cared for patients with acute leukemia do not have ATRA immediately available. Moreover, the vast majority of hospitals that refer patients to other centers do not have ATRA. These findings should spur investigation into the impact of immediate ATRA availability on the morbidity and mortality of patients with APL. A call by hematologists nationwide to their formulary committees is warranted to ensure that this lifesaving medication is available to patients suspected of having APL.

Tenalisib (RP6530), a dual phosphoinositide 3-kinase &delta, /&gamma, inhibitor was evaluated in a phase I/Ib study for maximum tolerated dose (MTD), pharmacokinetics, and efficacy in patients with relapsed/refractory peripheral and cutaneous T-Cell Lymphoma (TCL). Histologically confirmed (TCL) patients, with &ge, 1 prior therapy received Tenalisib orally in a 28-day cycle in doses of 200 to 800 mg twice daily (800 mg in fasting and fed state) in escalation phase (n = 19) and 800 mg twice daily (fasting) in expansion phase (n = 39). The most frequently reported treatment emergent adverse events (TEAE) and related TEAE were fatigue (45%) and transaminase elevations (33%), respectively. Most frequently reported related Grade &ge, 3 TEAE was transaminase elevation (21%). Two dose-limiting toxicities occurred in the 800 mg fed cohort, hence, 800 mg fasting dose was deemed MTD. Tenalisib was absorbed rapidly with a median half-life of 2.28 h. Overall response rate in 35 evaluable patients was 45.7% (3 complete response (CR), 13 partial response (PR)) and median duration of response was 4.9 months. Responding tumors showed a marked downregulation of CD30, IL-31 and IL-32&alpha, With an acceptable safety and promising clinical activity, Tenalisib can be a potential therapeutic option for relapsed/refractory TCL. Currently, a phase I/II combination study with romidepsin is ongoing.

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a phase 1b, dose-escalation study to assess the safety and preliminary efficacy of AFM13 in combination with pembrolizumab in patients with R/R HL. The primary objective was estimating the maximum tolerated dose; the secondary objectives were to assess safety, tolerability, antitumor efficacy, pharmacokinetics, and pharmacodynamics. In this heavily pretreated patient population, treatment with the combination of AFM13 and pembrolizumab was generally well tolerated, with similar safety profiles compared to the known profiles of each agent alone. The combination of AFM13 with pembrolizumab demonstrated an objective response rate of 88% at the highest treatment dose, with an 83% overall response rate for the overall population. Pharmacokinetic assessment of AFM13 in the combination setting revealed a half-life of up to 20.6 hours. This proof-of-concept study holds promise as a novel immunotherapy combination worthy of further investigation. This phase 1b study was registered at www.clinicaltrials.gov as NCT02665650.

7505 Background: MCL is a rare lymphoma without a standard of care but several regimens have demonstrated clinical activity, the majority based on traditional chemotherapy. We hypothesized that adding venetoclax (V) to R2 would be safe and effective in MCL pts irrespective of age, morphology or stage. Here we present safety and efficacy data from the on-going phase 1b study of R2 + V in pts with newly diagnosed MCL. Methods: This multi-center phase 1 study (NCT03523975) enrolled pts aged ≥18 yrs with untreated MCL. The primary objective was to characterize the safety and tolerability of R2 + V and determine the MTD. During induction (12 months (m)) pts received lenalidomide (L) 20 mg daily on day 1-21, Rituximab (R) was given weekly during c1 then on day 1 of every even cycle, V was escalated over 4 weeks to 400 mg beginning day 8. Each cycle is 28 days (d). The DLT period was 42 d beginning C1D8. In maintenance, R every 8 weeks for 36m, L at 10 mg or half of last dose during induction for 24 m and V for minimum 12 m. No pts have been transplanted. Pts with progression (PD) came off study. MRD was analyzed in parallel with scans during induction by clonoSEQ assay (Adaptive Biotechnologies). Results: As of Feb. 1st, 2021, we have enrolled all 28 planned pts on study. Pt characteristics/responses are summarized in Table. Among the 28 pts who have received at least one dose, the median treatment duration so far is 278d (IQR 170-560), with 24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment-emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all-grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non-evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD - at 10-6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD - in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. Clinical trial information: NCT03523975. [Table: see text]

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of extranodal lymphomas involving the skin. Diagnosis of the two main subtypes of CTCL-mycosis fungoides (MF) and Sézary syndrome (SS)-is based on the International Society for Cutaneous Lymphomas/European Organization for Research and Treatment of Cancer (ISCL/EORTC) classification system, which utilizes clinical, histopathological, molecular biologic, and immunopathologic features. Risk stratification, based on TNMB (tumor, node, metastasis, and blood) staging, provides prognostic information, with limited-stage disease conferring the longest median overall survival. Skin-directed therapies are preferred in the management of limited-stage disease, whereas advanced-stage disease requires systemic therapies. As the mechanisms of CTCL pathogenesis are increasingly understood, new monoclonal antibodies, checkpoint inhibitors, immunomodulatory agents, and small molecules are under investigation and may provide additional therapeutic options for those with advanced CTCL. This review examines the current landscape of targeted therapies in the treatment of CTCLs.

Advanced classical Hodgkin lymphoma (cHL) is a rare lymphoid disease characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells. Each year, cHL accounts for 0.5% of all new cancer diagnoses and about 80% are diagnosed with advanced stage disease. Given the significant improvement in cure rates, the focus of treatment has shifted towards minimization of acute and long-term toxicities. PET-adapted strategies have largely been adopted as standard of care in the United States in an attempt to balance toxicities with adequate lymphoma control. However, the appropriate upfront chemotherapy regimen (ABVD versus eBEACOPP) remains controversial.

Optimal salvage therapy for primary refractory peripheral T-cell lymphomas (PTCL) and the role of hematopoietic stem cell transplant (SCT) remain poorly defined. We conducted a retrospective review of clinical outcomes and prognostic factors in a single-center cohort of 93 patients with primary refractory PTCL, defined as progression during first-line therapy or relapse within 6 months of its completion. Clinical outcomes were poor in this population, with median event-free survival (EFS) of 3.5 months, median overall survival (OS) of 9.1 months, and 34% 3-year survival. Outcomes were comparable in patients who progressed through first-line therapy and patients who achieved CR/PR and subsequently relapsed within 6 months. A majority exhibited high-risk features and had intermediate to high risk IPI, which correlated with inferior outcomes. There was no difference in outcomes between patients who received single-agent salvage regimens and patients who underwent traditional, multi-agent salvage regimens. Thus, participation in well-designed clinical trials should be encouraged in this population. Additionally, there may be a trend toward improved EFS and OS in patients who underwent autologous or allogeneic SCT compared to patients who achieved CR or PR but were not transplanted.

Successful treatment of relapsed/refractory and rare subtypes of lymphomas remains a therapeutic challenge. Though the use of tumor profiling is increasing, little is described about how providers ...

e14645 Background: Despite the increasing availability of targeted and novel therapies, successful treatment of many relapsed/refractory lymphomas remains a challenge. Tumor sequencing is becoming an increasingly available technique to identify potential therapeutic targets; however, there remains considerable uncertainty about the successful application of this data in a “real world” clinical setting. Methods: Herein, we describe 91 lymphoma patients who underwent DNA & RNA sequencing of tumor biopsies via the MIONCOSEQ protocol to identify actionable therapeutic targets. Their charts were reviewed for the clinical use of MIONCOSEQ recommendations. Results: Among the 91 patients were 13 Lymphoma subtypes. Most patients had Stage III/IV disease (68%) at diagnosis, underwent an average of 4 treatments before sequencing (range 0-16) and had approximately 47 distinct molecular alterations (range 2-447). Of the cohort, 60 patients (65%) had actionable targets identified of which 11 ultimately received treatment based on MIONCOSEQ recommendations. The remaining patients did not receive treatment due to multiple reasons: prior CR or on surveillance not requiring treatment (10); death (12); trial ineligibility (4); trial unavailability at the institution (8); patient preference for local treatment (6); and already on alternative treatments (9). Taken as a whole, sequencing late in the disease course and a lack of available clinical trials were identified as barriers for the incorporation of MIONCOSEQ data into clinical practice. Therefore, earlier sequencing and strategies to bolster the availability of targeted therapies may significantly increase the application of genomic data and precision medicine in clinical practice. Conclusions: While next generation sequencing (NGS) is a powerful tool for advancing precision medicine, meaningful clinical application of these results remains a challenge. Our study indicates that early sequencing and improved trial availability could be beneficial in increasing real-world therapeutic options for relapsed/refractory lymphoma. Further research is needed to determine the extent to which a personalized approach, informed by NGS data, improves outcomes.

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a devastating disorder with protean clinical manifestations caused by the overproduction of T-cell derived cytokines. Cytokine-dependent activation of the Janus family kinases (JAK) is a hallmark of the final common pathway in HLH pathogenesis. Therefore, we initiated a single center, open-label, investigator-initiated trial to assess the efficacy and safety of ruxolitinib in adult patients with secondary HLH. Methods: Adult patients (≥18 years) who fulfilled 5 of 8 diagnostic criteria were eligible. Patients with CNS involvement or an active malignancy were ineligible. Patients who had received any prior systemic therapy (excluding corticosteroids) within 7 days of treatment were ineligible. Patients with normal renal function received oral ruxolitinib 15 mg twice daily on a continuous, 28-day cycle. Dose reductions for renal insufficiency and toxicity are permitted. Treatment was continued indefinitely until disease progression, unacceptable toxicity, or any other conditions for treatment discontinuation were met. The first patient was enrolled in February, 2016 and enrollment is ongoing. The primary endpoint is overall survival at 2 months. Secondary endpoints include the response rate, duration of response, progression-free and overall survival. Adverse events were graded and attributed in accordance with the National Cancer Institute Guidelines for the Cancer Therapy Evaluation Program. Disease parameters evaluable for response included all quantifiable signs and laboratory abnormalities included in the diagnostic criteria for HLH. A complete response (CR) required normalization of all signs and laboratory abnormalities. At least 25% improvement in two or more signs/laboratory abnormalities was required for a partial response (PR). At least a 50% worsening in two or more signs/laboratory abnormalities was considered progressive disease (PD), while failure to fulfill any of these criteria was considered stable disease (SD). Results: A total of 4 patient have been enrolled, all of whom fulfilled at least 5 of 8 diagnostic criteria for HLH. Hemophagocytosis, a pathologic hallmark of HLH, was observed in every patient. At the time of treatment initiation, all patients were anemic [median hemoglobin 7.1 g/dL (range: 6.2-7.5 g/dL)] and thrombocytopenic [median platelet count 47 K/uL (range: 14-107 K/uL)]. Three patients were neutropenic [median ANC 0.95 K/uL (range: 0-1.9 K/uL)]. HLH was secondary to an autoimmune disorder (n=3), infection (n=1), and a homozygous mutation in the STXBP2 gene, recently identified as a causative defect in primary HLH, was observed in one patient. Cytopenias significantly improved within the first week of treatment in all patients. On day +7, the mean increase in hemoglobin was 1.88 g/dL (0.2-3 g/dL), in ANC was 1.53 K/uL (range 0.1-5.3 K/uL) and platelet count was 74 K/uL (range 17-116 K/uL). Neutropenia resolved by day +40 and thrombocytopenia resolved by day +47 in all patients. Three of four patients became transfusion independent within 2 days of treatment initiation. Three of four patients received corticosteroids prior to and after initiation of ruxolitinib. The mean corticosteroid (prednisone equivalent) dose prior to treatment initiation was 225 mg/day (range: 60-391 mg/day) and was 38 mg/day (range: 0-75 mg/day) on day +30. Within 47 days of treatment initiation, corticosteroids were discontinued in 2 patients, and were discontinued in all patients by day +54. Significant improvements in ferritin and sIL-2R were also observed with a median 92.6% decrease in ferritin by day +30 (range 86.4-92.6%) and 86% median decrease in sIL-2R by day +30 (range 66.6-92.7%). All patients achieved at least a PR, and 2 patients remain on treatment (>2 months, >8 months). Two patients discontinued treatment, one for progressive disease (due to recurrent symptoms), and another for drug intolerance (neuropathic foot pain). No severe adverse events have been observed. In addition to the patients enrolled in this study, two additional patients who met eligibility criteria were similarly treated (off study) at another institution. Both of these patients achieved at least a PR and remain on treatment (>8 months, >14 months). Conclusions: Ruxolitinib led to rapid and durable responses and was well tolerated in adult patients with secondary HLH. Disclosures Devata: Affimed: Research Funding. Phillips:Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding; Genentech: Consultancy; Bayer: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy. Sood:Bayer: Research Funding. Wilcox:Incyte, Corp: Research Funding.

Background AFM13 is a bispecific, tetravalent NK cell-engaging antibody construct binding to CD30 on CD30+ tumor cells and CD16A on NK cells. By engaging CD16A-positive NK cells, AFM13 leads to NK cell-mediated killing of CD30-positive lymphoma cells (Reusch et al., 2014) making it an attractive agent to target classical Hodgkin lymphoma (HL). Pembrolizumab is a PD-1 blocking antibody which has shown high single-agent response rates in patients (pts) with relapsed/refractory HL (RRHL; Armand et al., 2016, Chen et al., 2017). AFM13 has shown clinical activity in RRHL as a single agent in a preceding Phase 1 study (Rothe et al., 2015). Preclinical in vivo data of the combination of AFM13 with PD-1 blockade showed synergistic activity and the potential for induction of cross-talk between innate and adaptive immunity (Zhao et al., 2016). We hypothesize that the combination of the two agents could improve outcomes in pts with RRHL. Methods This Phase 1b study is evaluating the safety and tolerability of the combination of AFM13 with pembrolizumab (Keytruda) as salvage therapy after failure of standard therapies including brentuximab vedotin (BV) in HL (NCT02665650). Pts receive escalating doses of AFM13 in combination with pembrolizumab at a dose of 200 mg flat administered every 3 weeks following a classical 3+3 design, followed by enrollment into an extension cohort at the maximum tolerated dose (MTD)/maximum administered dose (MAD). Response assessment is performed every 12 weeks by PET/CT according to the Lugano Classification (Cheson et al., 2014). The main objectives of the study is to ascertain the MTD/MAD along with the preliminary efficacy of the combination. Results As of June 29, 2018, 30 pts have been enrolled into the study. The median age is 34 years (range, 18-73), with a median of 4 (range 3-7) prior lines of therapy. All pts had relapsed or refractory disease (43% relapsed, 57% refractory) and had failed standard treatments including BV and 43% of pts (13/30) had BV as their latest therapy. Thirty seven percent (11/30) had undergone prior autologous stem cell transplantation. All 30 pts have completed the 6-week dose-limiting toxicity (DLT) observation period. Twelve pts were enrolled into the dose escalation cohorts (Cohorts 1 (n=3), 2 (n=3), and 3 (n=6)) and 18 into the Extension Cohort, with a total of 24 patients treated at the MAD (dose level 3). One DLT was observed in Cohort 3 (missing ≥25% of AFM13 during the DLT period) and another observed in the Extension Cohort (G4 infusion-related reaction; IRR). The most common related adverse events (AEs) were IRRs (80%), rash (30%), pyrexia (23%), nausea (23%), diarrhea (20%), fatigue (17%), headache (17%), increased aspartate aminotransferase (13%), and increased alanine aminotransferase (10%). Treatment related G3/4 AEs included IRRs (13%), elevated AST (3%), gastritis (3%), hypotension (3%), nausea (3%), neutropenia (3%), and vomiting (3%). The majority of IRRs were manageable with standard of care measures and did not lead to treatment discontinuations. Included in the efficacy analysis were the best response from 29 evaluable pts who had at least one post-baseline disease assessment as of the data cutoff on June 29, 2018. The overall response rate (ORR) and complete response (CR) rate for evaluable pts treated at the dose and schedule chosen for expansion (n=23; Cohort 3 and Extension Cohort) were 87% and 35% by the investigator-confirmed assessment, respectively. Independent assessment resulted in an ORR of 87% and CR rate of 39% for these pts. Updated data for all 30 patients will be presented at the meeting. Conclusions The combination of AFM13 and pembrolizumab is a well-tolerated salvage therapy in pts with RRHL. IRRs were the most frequently observed adverse events; however, most of these events were of mild or moderate severity and manageable. Both the ORR and CR rate compare favorably to monotherapy pembrolizumab in a similar RRHL population (Chen et al., 2017). The combination of AFM13 and pembrolizumab could be a potential new therapeutic option for HL patients. Disclosures Bartlett: Immune Design: Research Funding; Affimed: Research Funding; Bristol-Meyers Squibb: Research Funding; Merck & Co: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Novartis: Research Funding; Novartis: Research Funding; Millennium: Research Funding; ImaginAB: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees. Chen:Affimed: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech Inc.: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck & Co., Inc.: Consultancy, Research Funding, Speakers Bureau; Millennium Pharmaceuticals: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding. Domingo-Domenech:Affimed: Research Funding. Forero-Torres:Affimed: Research Funding. Garcia-Sanz:Affimed: Research Funding. Devata:Affimed: Research Funding. Rodriguez Izquierdo:Affimed: Research Funding. Lossos:Affimed: Research Funding. Reeder:Affimed: Research Funding. Sher:Affimed: Research Funding. Choe-Juliak:Affimed: Employment. Prier:Affimed: Research Funding. Schwarz:Affimed: Employment. Strassz:Affimed: Employment. Alland:Affimed: Employment. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Takeda: Research Funding.

Introduction Tenalisib (RP6530) is a next generation, oral, selective, PI3Kδ/g inhibitor with nanomolar inhibitory potency. Besides its apoptotic and anti-proliferative activity, Tenalisib modulates the tumor microenvironment resulting in reprogramming of tumor associated-macrophages (TAMs) from a protumor M2 phenotype to an antitumor M1 phenotype and a marked reduction of angiogenesis in pre-clinical models. Tenalisib has demonstrated activity in patients with relapsed/refractory lymphoid malignancies (Carmelo, ASH 2016 and Oki, ASCO 2018). Since there are concerns over long-term safety of PI3K δ or PI3K dual δ/g inhibitors with respect to immune-mediated toxicities (e.g. transaminitis, colitis and pneumonitis), cytopenias, and infections, a pooled safety analysis across two Phase I studies in patients treated with Tenalisib was performed. Methods Safety data was pooled from two Phase I Tenalisib monotherapy trials (NCT02017613 and NCT02567656) with similar key eligibility criteria. Patients had R/R lymphoid malignancies with ≥1 prior therapy. Responses were evaluated in lymphoid malignancies using IWG criteria (Cheson et al., 2007) and in CTCL using the modified Severity Weighted Assessment Tool (mSWAT). Adverse events were graded according to CTCAE v4.03. Results A total of 93 patients were included in the analysis. Among these patients, 34% were PTCL, 32% CTCL, 16% HL, 6% DLBCL and 12% were other lymphomas. Patients received a median of 5 prior therapies. 53 % of patients received Tenalisib for ≤ 3 months, 21% for 3-6 months and 26% for > 6 months. The overall incidence of related AEs and ≥G3 AEs were 58% and 29% respectively (Table 1). Very few AEs were seen with exposures >6 months and mainly included single cases of diarrhea, anemia, edema, and abdominal pain. There were no incidences of late onset toxicities such as colitis and pneumonitis and most of the AEs happened during the initial three months of therapy. No treatment discontinuations due to AE's were seen in patients exposed to > 6 months of treatment. Efficacy response assessments of the 66 evaluable patients demonstrated an ORR of 45% in TCL (44% in PTCL (8/18, 3 CR, 4 PR) & 45% in CTCL (9/20, 9 PR)), 29% (4/14; 1CR; 3PR) in HL, and 13% (1/6; 1CR) in DLBCL. Conclusion In this pooled safety analysis with long term follow-up, Tenalisib exhibited an improved safety profile when compared to other investigational/marketed PI3K inhibitors. The incidence of transaminitis was low and occurred within the first two to three cycles of therapy. In particular, there were no occurrences of pneumonitis or colitis in patients that had been on treatment for > 3 months and beyond. Incidence of neutropenia/thrombocytopenia and infections was limited. Tenalisib can therefore be safely combined with a diverse array of other agents active in lymphoid malignancies. Tenalisib is currently being studied in combination with Pembrolizumab and Romidepsin and as a monotherapy in a Phase II trial in indolent NHL. Disclosures Haverkos: Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees. Ramchandren:Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Merck: Research Funding; Janssen: Consultancy, Research Funding. Devata:Affimed: Research Funding. Routhu:Rhizen Pharmaceuticals SA: Employment. Barde:Rhizen Pharmaceuticals SA: Employment. Nair:Rhizen Pharmaceuticals SA: Employment. Carlo-Stella:Boehringher Ingelheim Italia: Consultancy; Sanofi: Consultancy; MSD Italia: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; AstraZeneca: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Genenta Science: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Amgen: Speakers Bureau.

Pancreatic neuroendocrine tumors (PNETs) are relatively rare tumors that arise in the endocrine cells of the pancreas. Historically, somatostatin analogues have been used in this disease primarily for symptom control and, to a limited extent, disease stability. More recently, sunitinib and everolimus have been approved for advanced stage PNETs based on a survival benefit. However, both agents have a

The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin’s lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targeting this immune checkpoint. While further studies are needed, the available data suggests that responses with PD-1 checkpoint blockade alone will unlikely approach those achieved in other lymphoproliferative disorders. Herein, we review the unique challenges posed by the T-cell lymphoproliferative disorders and discuss potential strategies to optimize checkpoint blockade in these T-cell derived malignancies.

e23169 Background: Personalized therapy through the identification of targetable mutations within individual tumors has increasingly become a focus in the management of patients (pts) with relapsed/refractory malignancy. To better understand how this is clinically applied, we reviewed 29 cases of B- and T-cell lymphomas that had genetic sequencing of their tumor. Methods: The electronic medical records of 29 pts who underwent Michigan Oncology Sequencing (MI-ONCOSEQ) testing at the University of Michigan from 2013-2016 were reviewed for disease and treatment history. Reports from whole-genome tumor sequencing were obtained for each patient to identify putative molecular targets. Results: Sixteen male and 13 female pts had a median age of 59 years (range 30-80 years) and median disease stage of IV at diagnosis. Five had CTCL, 5 PTCL, 11 follicular, 1 CLL/ mantle cell (MC), 1 MC, 1 marginal zone, 1 Waldenstrom’s (WM) and 4 DLBCL. Pts received a median of 2 therapies prior to MI-ONCOSEQ biopsy. Targetable mutations were identified in 15 pts and a total of 5 pts underwent MI-ONCOSEQ-based treatments. Bosutinib was given for FYB-FGR fusion, imatinib for FLI1-PDGFRB fusion, and everolimus for activating mTOR mutation with an avg. treatment duration of 3.6 weeks due to progressive disease. Bosutinib and imatinib were 3rd line therapies and everolimus was 5th. Another 2 pts were treated with ibrutinib for transformed WM with MYD88 mutation and bortezomib after classification of DLBCL as ABC-type based on MI-ONCOSEQ results, with CR in both. Other targetable mutations identified include BRAF, CDK, BCL2, EZH2 and NOTCH. Of the remaining 12 pts with targetable mutations, 8 pursued clinical trials, 2 responded to standard therapy, 1 died shortly after genetic analysis and 1 declined further therapy. About 50% of these pts remain alive. Conclusions: Our results demonstrate that targeted therapy is favored after standard therapy or clinical trial options are exhausted. Barriers to its use include the availability of clinical trials, off-label drug access and our incomplete knowledge of driver mutations. With further understanding of disease pathogenesis, we expect personalized therapy will be possible for all patients.

Background : Selectins, among other adhesion-mediated functions, facilitate and augment thrombosis; standard anticoagulants address thrombosis but also increase bleeding risk. Previous work in animal models showed inhibiting E-selectin decreases venous thrombosis (VTE) and vein wall inflammation without adverse bleeding events, making E-selectin inhibition a favorable therapeutic candidate for VTE. GMI-1271 is a potent, specific E-selectin antagonist. Here we report final analysis of safety, PK, biomarker and bleeding risk profile for GMI-1271 in 2 phase 1 studies of healthy subjects. Methods: The first study was a blinded single ascending dose (SAD) evaluation of 2, 5, 20, or 40mg/kg of GMI-1271 (n=4/cohort), vs placebo control saline (n=4) or active control Lovenox 1mg/kg (n=4). The second was an open-label multiple ascending dose (MAD) study of 10 (n=3) or 20mg/kg (n=3) of GMI-1271 QD d 1-5 vs Lovenox 1mg/kg (n=2) d 1-5. Assessments included safety (adverse events [AEs], clinical labs, bleeding time, PT/PTT, vitals, exam); PK (plasma and urine); and biomarkers. Biomarkers included ELISAs (CRP, D-dimer, IL-10, MPO, Prothrombin fragment 1.2, soluble E-selectin (sEsel), soluble P-selectin (sPsel), sICAM, Thrombin-antithrombin complex (TAT), Tissue Factor (TF), TNFα, VWF activity, and sCD40L); PicoGreen Assay for circulating DNA; flow cytometry (Platelet Monocyte Aggregates (PMA), Mac-1, LFA-1, and CD44) and Thromboelastography (TEG). See Table 1 for functional description. SAD remains blinded to GMI-1271 or placebo (GMI-1271/p). In SAD, we measured biomarker values at baseline, 8 and 24 h after dosing. Analysis was performed of biomarkers at each dose level and then pooled by GMI-1271/p vs Lovenox. In MAD, we measured biomarker values at baseline and day 4. Comparisons were made using unpaired t-test. Results: In total, 32 subjects enrolled and received GMI-1271/placebo (GMI-1271/p; 20), GMI-1271 (6) or Lovenox (L; 6). Safety: All subjects completed dosing uneventfully. Safety findings for GMI-1271/p were unremarkable. No moderate or serious AE were seen. AE overall were as expected in healthy volunteers. In SAD, only 1/20 GMI-1271/p subjects experienced an AE possibly related to study drug (mild transient headache); 0/6 in MAD. In the L group we saw expected mild transaminitis and injection site bruising. In all studies, GMI-1271 had no effect on bleeding time, PT, or PTT. PK: Plasma levels, Cmax, and AUC increased in a linear manner. Cl, Vz, and t ½ were not dose dependent; no accumulation was seen with multiple dosing (Fig 1 and 2). TEG: In SAD, there was a tendency to increase R, K, and decrease A and MA with no change in % lysis in L vs GMI-1271/p. In MAD, we saw a similar trend as SAD except for an increase in % lysis in L. In the pooled SAD analysis, there was a statistically significant difference between GMI-1271/p and L (higher values) for R (p sEsel: In SAD, there was a trend for sEsel to decrease with treatment in all cohorts (combined GMI-1271/p vs L p= 0.017). In MAD, there was non-significant trend for sEsel to decrease between Day 0 and Day 4 in GMI-1271; sEsel levels trended upward with L in comparison. MPO: In SAD, there was a trend for increased values in L vs GMI-1271/p, except for the 40mg/kg cohort. When pooled, there was a significant difference between GMI-1271/p vs L (higher levels) p MAC-1 In SAD, there was no change. In MAD, there was a significant decrease in MAC-1 at the 10mg/kg dose (p No other notable trend was seen in the other biomarkers measured. Conclusion: We report a favorable safety, biomarker and bleeding profile for the E-selectin antagonist GMI-1271 in healthy subjects. There is no signal to suggest GMI-1271 increases bleeding potential based on adverse events, PT, PTT, bleeding time, and TEG values, unlike traditional anticoagulants. An additional unblinded analysis of the biomarkers will be presented at ASH. We note a trend for sE-sel to decrease with GMI-1271 treatment even in this healthy volunteer population, consistent with previous experience and as expected based on mechanism of action. A phase 1 study of GMI-1271 is currently ongoing to evaluate the safety and efficacy of E-selectin antagonism for the treatment of patients with calf vein DVT. PK Figures: Figure 1: SAD; Figure 2: MAD. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Hemmer: GlycoMimetics, Inc.: Employment, Equity Ownership. Flanner:GlycoMimetics, Inc.: Employment. Parker:GlycoMimetics, Inc.: Employment. Li:GlycoMimetics, Inc.: Employment, Equity Ownership. Froehlich:Novartis: Consultancy; Janssen: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Membership on an entity's Board of Directors or advisory committees; Fibromuscular Disease Society of America: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Merck: Consultancy. Magnani:GlycoMimetics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Thackray:GlycoMimetics: Employment, Equity Ownership. Sood:Bayer: Research Funding.

Background: Resistance to conventional anthracycline-based regimens (CHOP/CHOEP) and the emergence of primary refractory disease remains a clinical challenge in PTCL, and is observed in ≈25% of patients. Outcomes in the setting of primary refractory disease, particularly for those patients who fail to achieve a remission with second-line chemotherapy, are poorly described and the optimal therapeutic strategy for these patients remains uncertain. Patients and Methods: We identified 159 patients with PTCL who received multi-agent, anthracycline-based treatment from 1988 to 2011 in the PTCL database at our institution. Primary refractory disease, defined as disease progression during initial therapy or relapse within 6 months of its completion, was observed in 58 (36%) of patients. Results: The median age at diagnosis with primary refractory PTCL was 49 years (range, 18.8-77.1). Median follow up was 2.7 years among surviving patients (95% CI, 1.2-6.3). Median overall survival (OS) was 1.1 years (95% CI, 0.7-1.9). The median number of lines of therapy underwent by patients was 3 (range, 1-9). PTCL, NOS (n=24), angioimmunoblastic T-cell lymphoma (n=6), and ALK-positive anaplastic large cell lymphoma (n=7) accounted for the majority (63.8%) of these patients. No difference in OS was observed between patients who failed to respond to initial therapy and those who relapsed within 6 months after a first remission (median OS 0.9 [95% CI, 0.6-1.9] vs. 1.3 [95% CI, 0.5-6.3], p=0.6). After developing primary refractory disease, 48.3% of patients received aggressive, multi-agent salvage regimens (ICE, n=16; DHAP, n=3; ESHAP, n=6; other, n=3), 29.3% of patients received other systemic therapies (HDAC inhibitor, n=1; gemcitabine-based therapies, n=5; pralatrexate, n=3; other, n=8), and 22.4% of patients received no systemic therapies. Patients who received no systemic salvage therapy had reduced OS compared to both patients who received aggressive regimens and patients who received other types of systemic therapies (median OS 0.3 [95% CI, 0.2-1.1] vs. 1.7 [95% CI, 0.8-11.7] vs. 1.3 [95% CI, 0.4-8.6], respectively, p Conclusion: Primary refractory PTCL is associated with dismal outcomes. The likelihood of achieving a remission and proceeding to transplant is ≈30% and with transplant, only 11 (19% of patients with primary refractory disease) achieved a durable remission. Improved understanding of resistance mechanisms in PTCL and the development of improved therapeutic strategies are needed. A significant survival benefit was not observed for patients receiving traditional salvage regimens compared to other systemic second-line regimens, with median survival Disclosures No relevant conflicts of interest to declare.

The cytokine interleukin-6 (IL-6) has been implicated as a contributor to injury in several neurological disorders. The amounts of IL-6 released by the cerebral cortical tissue of mice of varying maturational age groups were measured and found to increase with age. Specifically, the basal level of IL-6 released from the tissue of infant (less than 2 weeks old) mice was low, although the tissue could be readily stimulated to secrete high levels of IL-6. Higher levels of IL-6 were released from young adult (2 month old) mice. Adult mice that were either 6 or 9 months of age secreted significantly higher levels of IL-6 compared to the tissue of either the young adult or infant animals, although the difference between levels secreted by the 6- or 9-month old groups was minimal. IL-6 production by adult cerebral cortical tissue could be further stimulated, but it was less readily achieved compared to the tissue of infants. In response to the negative regulator transforming growth factor-beta (TGF-beta), the levels of IL-6 released by stimulated cerebral cortical tissue of infants, as well as by unstimulated and stimulated tissue of adults, were reduced to the low basal levels of IL-6 produced by infant tissue. These results suggest that normal development and aging are correlated with an increase in IL-6 production that may be due to shifts in levels of stimulatory or inhibitory regulatory controls, but not to an inability of young tissue to produce IL-6 or to a lack of responsiveness of adult tissue to negative regulatory control by TGF-beta.

Background: GMI-1271 is a potent, specific E-selectin antagonist which targets interactions between cancer cells and the bone marrow niche thereby increasing tumor sensitivity to chemotherapy; avoids HSC mobilization; and inhibits thrombosis without increasing bleeding risk. Delayed inflammatory cell recruitment into the vein wall post thrombus induction indicates a possible decrease in leukocyte activation, which may be crucial in treating both acute and cancer associated thrombosis. Here we report first-in-human evaluation of GMI-1271 for safety (including bleeding), PK, and biomarker data for effects on adhesion and mobilization. Methods: Two Phase I single dose escalation DBRCT in healthy subjects evaluated 2, 5, 10, and 20 mg/kg IV doses of GMI-1271. Study 1 is complete and unblinded (GMI-1271 vs placebo). Study 2 is ongoing, remains blinded (GMI-1271 vs placebo) with open-label positive control (Lovenox), and is reported in aggregate. In both studies, assessments included safety (adverse events [AEs], clinical labs, bleeding time, PT/PTT, vitals, and exam); PK (drug levels in plasma and urine); and biomarkers (plasma soluble E-selectin [sEsel], sPsel, sICAM-1 levels; and blood CD34+ counts). Only sEsel and CD34+ are reported for Study 1; sEsel, sPsel, sICAM-1 for Study 2. Comparisons to baseline were made by ANOVA and paired t-test models; PK analyses were for total clearance (CL), volume of distribution (Vz), elimination half-life (t½), fraction excreted (Fe), and renal clearance (CLr). Results: Forty-six subjects enrolled; 30 received GMI-1271 (10 each at 2 and 5 mg/kg; 6 at 10 mg/kg; and 4 at 20 mg/kg) and 16 received control (13 placebo, 3 Lovenox). Safety: All subjects completed the studies; labs, vitals, and exam were unremarkable. Bleeding times and PT/PTT were unaffected by E-selectin inhibition. No serious AEs were seen. For Study 1, AEs were seen in 12/18 (66.7%) of those on GMI-1271 and 5/10 (50%) on placebo. AEs were mostly mild events at the infusion site (i.e. tenderness or erythema), and occurred in both groups. One moderate AE occurred (vasovagal reaction) in the 2 mg/kg GMI-1271 cohort. Three AEs were possibly related to drug: 2 in the 2 mg/kg cohort (infusion site bruise, lightheaded), and 1 in the 5 mg/kg cohort (metallic taste). For Study 2, AEs were seen in 12/15 (80%) of those on GMI-1271/placebo and 3/3 (100%) on Lovenox. All AEs were mild. In GMI-1271/placebo group, all AEs were considered unrelated to study drug; 3 were infusion site bruise (1 per dose level). In the Lovenox group, AEs were bruise at injection site (related) and blood in urine (possibly related). PK: Plasma levels, Cmax, and AUC increased in a consistent dose-related manner in both studies (figure). CL, Vz, and t½ were not dose dependent; the latter averaged ~2.3 hours. ~66% of the dose was excreted unchanged in the urine independent of dose level, and CLr averaged 86 mL/min, less than estimated CrCl, suggesting tubular reabsorption is one component of CLr. Biomarkers: In Study 1, the absolute CD34+ and %CD34+ cell counts were normal across all cohorts. There was no dose-response for changes in peripheral CD34+ counts after administration of GMI-1271 (doses 2-10 mg/kg). Plasma concentrations of sEsel were relatively constant in the placebo and GMI-1271 2 mg/kg cohorts, with significant reduction (vs baseline, p=0.012) at 48hrs post-2mg/kg dose only. In the 5 and 10 mg/kg cohorts sEsel decreased significantly post-dose (p Conclusion: First-in-human experience with the potent E-selectin antagonist GMI-1271 demonstrated favorable safety and PK at single doses up to 20 mg/kg. These findings are consistent with the glycomimetic class for safety at anticipated therapeutic levels. Biomarkers of physiologic effect demonstrated clear reductions in sEsel/sPsel; decreased leukocyte adhesion with lower sICAM-1 levels; and no CD34+ rise indicating no mobilization of HSCs. Studies of GMI-1271 are ongoing to evaluate activity in hematologic malignancies and thrombosis. Figure 1. Plasma concentrations and Cmax are consistent for GMI-1271 between Phase 1 studies. Figure 1. Plasma concentrations and Cmax are consistent for GMI-1271 between Phase 1 studies. Disclosures Sood: Bayer: Research Funding. Hemmer:GlycoMimetics: Employment, Equity Ownership. Flanner:GlycoMimetics: Employment, Equity Ownership. Kramer:GlycoMimetics: Consultancy. Nietubicz:GlycoMimetics: Employment, Equity Ownership. Myers:GlycoMimetics: Research Funding. Wakefield:GlycoMimetics: Research Funding. Magnani:GlycoMimetics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Thackray:GlycoMimetics: Employment, Equity Ownership.

A 60-year-old Caucasian female presented with stage IIA (T2N0M0) estrogen- and progesterone-negative and HER2-positive breast cancer. She was started on an adjuvant chemotherapy regimen of docetaxel, carboplatin, and trastuzumab (TCH). She tolerated the first two cycles of the TCH regimen well. However, 3–4 days after the third and fourth cycles, she developed acute pancreatitis. Elevated pancreatic enzymes and abdominal computed tomography (CT) imaging findings confirmed the diagnosis of acute pancreatitis. Common causes of pancreatitis were ruled out. Given the time course it was assumed that the chemotherapy was the cause of pancreatitis in our patient. The patient did not receive any further docetaxel and carboplatin chemotherapy but continued on adjuvant trastuzumab alone for a planned duration of 1 year without any recurrence of acute pancreatitis.

Background: Diffuse large B-cell Lymphoma (DLCBL) is a heterogeneous disease. Current prognostic models have limitations, but emerging research utilizing the cell of origin and host immune factors, such as the absolute monocyte count (AMC) and absolute lymphocyte count (ALC), may improve risk stratification in these patients. In the rituximab era, the majority of relapses are observed within the first 24 months following treatment. Therefore, event free survival at 24 months (EFS24) is a reliable surrogate for overall survival in DLBCL [Maurer et. al., J Clin Oncol, 2014 Apr 1; 32(10): 1066-73]. The primary objective of this study was to determine if the ALC/AMC ratio predicts EFS24 in DLBCL risk-stratified by the cell of origin (COO). Methods: Patients with de novo DLBCL who were evaluated at the University of Michigan Comprehensive Cancer Center between 1997 and 2011 and had archived diagnostic tissue available were eligible for participation in this retrospective study. We identified 243 eligible patients. The ALC and AMC were obtained from a complete blood count with differential at the time of diagnosis. Immunohistochemical staining for CD10, Bcl-6 and IRF4/MUM1 was performed and cases independently scored in a blinded fashion by up to three hematopathologists. A consensus opinion was obtained in order to determine the cell of origin (COO) using the Hans algorithm. Results: The median age at diagnosis was 61 years with a median follow-up of 3.1 years. Among the 218 patients for whom the revised IPI could be calculated, 46% were high risk (IPI 3-5). Most patients received rituximab based chemoimmunotherapy (88%), largely R-CHOP (81%). The median ALC/AMC ratio for the entire cohort was 2 (interquartile range: 1-3). The ALC/AMC ratio was analyzed as a continuous variable on univariate analysis and was associated with inferior EFS (hazard ratio (HR) =0.81, 95% confidence interval (CI) 0.68-0.93, p=0.003). A receiver operating characteristic curve (ROC) was generated utilizing EFS24 to establish the optimal cut-off point for the ALC/AMC ratio. An ALC/AMC ratio of 1.6 was best able to risk-stratify patients for EFS24. The 24-month EFS for patients with an ALC/AMC ≥1.6 was 73% and for ALC/AMC Tissue exhaustion precluded determination of the COO for many patients. Among the remaining 112 patients, 63% were GCB and 37% non-GCB. Mean ALC/AMC ratios for the GCB and non-GCB subtypes were not significantly different at 2.2 and 2.4, respectively. Among GCB DLBCL the EFS24 and 5-year OS for ALC/AMC ≥1.6 vs ALC/AMC Conclusions: The ALC/AMC ratio is an independent prognostic factor for EFS24 in both GCB and non-GCB DLBCL. Disclosures No relevant conflicts of interest to declare.

e18575 Background: Maintenance therapy after AutoHCT improves progression free but not overall survival in MM. Close monitoring and preemptive treatment at biochemical progression may delay clinical relapse of MM while reducing overall drug exposure. However the interval from biochemical to clinical progression is not generally studied, and limits the feasibility of such a preemptive strategy. Methods: In order to analyze patterns of relapse after AutoHCT, we studied biochemical and clinical relapse in 97 AutoHCT recipients with MM. Patients (pts) were monitored with q 3mo serum free light chain, protein electrophoresis and annual bone studies interpreted by standard IMWG criteria. Results: Median age was 60 (47-77), 61% male and 20% with light chain myeloma. Characteristics of the upfront transplant cohort (69%) at diagnosis: International Staging System (ISS) Stage III in 41%, median values of beta2-microglobin (b2m) 3.26, albumin 3.8, high-risk cytogenetics in 35%. Recipients of salvage AutoHCT ( 31%) ...