Hernandez‐Ilizaliturri, Francisco J.

Background: The DIAL study is testing the efficacy of dual immunomodulation in patients with advanced aggressive B cell non-Hodgkin lymphoma (B-NHL). Sponsored by the Cancer Therapy Evaluation Program (CTEP), the trial combines the use of a programmed cell death protein 1 (PD-1) inhibitor (nivolumab) with an agonist of the CD27 receptor (varlilumab) in a randomized phase 2 design. CD27, a co-stimulatory receptor, regulates T cell activation in the context of T cell receptor (TCR) engagement through interaction with CD70. T cell exhaustion plays a major role in immune evasion in B-NHL. Varlilumab is an agonistic IgG1 monoclonal antibody that recognizes CD27 leading to prevention or reversal of exhaustion in pre-clinical models. Varlilumab also demonstrates direct anti-tumoral activity in xenograft models of human lymphoma cell lines via antibody-dependent cell-mediated cytotoxicity. Phase 1 data supports the safety and tolerability of single-agent varlilumab in advanced hematologic malignancies (NCT01460134). We hypothesize that CD27 activation synergizes with PD-1 inhibition resulting in a superior anti-lymphoma effect compared to PD-1 blockade alone. The study will also evaluate the effect of these agents on tumor and immune cells using immunohistochemistry (IHC), mass cytometry (CyTOF), multiplex ELISA, imaging mass cytometry (IMC), and whole exome sequencing. Methods: The trial is enrolling patients with advanced aggressive B-NHL. Standard inclusion criteria and prior treatment with at least 2 lines of standard therapy are required. Prior autologous stem cell transplant and/or chimeric antigen receptor (CAR) T cell therapy is allowed. Patients with active CNS disease are excluded. Eligible patients are randomized to treatment with single-agent nivolumab (group 1) or dual immunotherapy with nivolumab and varlilumab. Group 1 is allowed to cross-over at the time of progression. Nivolumab will be administered intravenously (IV) every 2 weeks (240 mg) for 4 months followed by monthly dosing thereafter (480 mg). Varlilumab will be given IV every 4 weeks (3 mg/kg). Response assessment will be done by PET-CT scan every 12 weeks. Primary outcome is overall response rate (ORR) according to the LYRIC criteria. The trial will enroll 48 patients per arm, allowing 80% power to detect at least 20% increase in ORR in the experimental arm (group 2) assuming a 25% ORR in the control arm (group 1). The trial is registered (NCT03038672) and open to participation to members of the Experimental Therapeutics Clinical Trials Network (ETCTN) and Early Drug Development Opportunity Program (EDDOP). Figure Disclosures Tun: BMS: Research Funding; Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding; Mundi-pharma: Research Funding; DTRM Biopharma: Research Funding. Bartlett:Pharmacyclics: Research Funding; Merck: Research Funding; Incyte: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Millennium: Research Funding; Kite Pharma: Research Funding; Janssen: Research Funding; Immune Design: Research Funding; Affimed: Research Funding; Autolus: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Forty Seven: Research Funding; Genentech, Inc.: Research Funding; Gilead: Research Funding. Kline:Merck: Honoraria; Merck: Research Funding. Awan:Janssen: Consultancy; Gilead: Consultancy; Sunesis: Consultancy; Genentech: Consultancy; Abbvie: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Speakers Bureau. Lazaryan:Kadmon: Consultancy. Ansell:Affimed: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Trillium: Research Funding. Diefenbach:Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding.

Abstract Introduction: Aggressive chemo-immunotherapy followed by peripheral blood stem cell autografting (ASCT) in CALGB (Alliance) 59909 achieved a median progression-free survival (PFS) in MCL of 5 years (Damon et al JCO, 2009), but late recurrences occurred. Using the CALGB 59909 treatment backbone, we evaluated tolerability and efficacy of adding post-transplant bortezomib consolidation (BC) or maintenance (BM)in a randomized phase II trial. Interim results of CALGB (Alliance) 50403 were previously presented (ASH 2015) demonstrating 5 yr PFS 70% and 69% for the BM and BC arms respectively. We now report final 8 year follow up results from this trial and compare outcomes to CALGB 59909, which differed from CALGB 50403 only by the absence of post-transplant bortezomib. Methods: The primary endpoint was PFS measured from randomization for each treatment arm. Induction therapy was with 2-3 cycles of augmented R-CHOP (2000 mg/m2 cyclophosphamide) and methotrexate (300 mg/m2) followed by high-dose cytarabine/etoposide/rituximab(R)/filgrastim (EAR) stem cell mobilization and cyclophosphamide/carmustine/etoposide (CBV) ASCT. After 2 doses of post-transplant R, patients were randomized to BC (1.3 mg/ m2 IV days 1, 4, 8, 11 of a 3-week cycle for 4 cycles) or BM (1.6 mg/m2 IV weekly x4 every 8 weeks for 18 months) beginning at approximately day 90. Minimal residual disease (MRD) was analyzed using patient-specific PCR probes for the bcl-1 / IgH junction or the IgH CDR3 region. Results: 151 patients were enrolled from 10/2006 - 6/2010 at 14 sites; 147 who received treatment are included in this analysis. Median age was 59 years (29-69); stage II (2.7%), III (11.6%), IV (85.0%); MIPI low (52.4%), intermediate (30.6%), high (17.0%); blastoid histology (12.9%); bone marrow involvement (81.0%); Ki67 was evaluated in 86 and was >30% in 17.4% of patients. 118 (80%) underwent ASCT and 102 (68%) were randomized. Most withdrawals (45) were for progression (10) or adverse events (AEs) (19) including 4 treatment-related deaths. Fifty-two patients were randomized to BM and 50 to BC. Following randomization, 34 (65%) completed BM and 33 (66%) completed BC. Withdrawal for AEs occurred in 14 (28%) of BC and 7 (13%) of BM patients (p = 0.09), most for cytopenias or peripheral neuropathy. With a median follow-up 7.8 years from randomization (8.3 from registration), the median PFS from randomization for the BM arm was not reached and was 8.9 years (95% CI 7.2 to not reached) for the BC arm. Both arms had median PFS significantly greater than the null hypothesis setting median PFS to 4 years (p < 0.001; 1-sided test of exponential parameter)The 8-year PFS estimates in the BM and BC arms were 77% (95% CI 66-90%) and 58% (95% CI 44-76%), respectively. Among all 147 patients treated on CALGB 50403, 8-year PFS from time of registration was 43.6% (35.6-53.3%). PFS from registration was not significantly extended in CALGB 50403 compared with CALGB 59909 (log rank p=0.24), but using a landmark analysis from time of transplant, PFS was significantly extended in CALGB 50403 (log rank p=0.005)(fig 1). Baseline patient characteristics in the two studies were not significantly different. In CALGB 50403, 8-year PFS from registration by MIPI was 52.0% (95% CI 41.1-66.0%) in MIPI low risk, 37.5% (95% CI 25.3-55.4%) in intermediate risk, and 28.2% (95% CI 13.7-57.9%) in high-risk. Bone marrow MRD results were collected for 42 patients post-induction therapy; 8-year PFS estimates were 80.2% (95% CI 62.2-100%) (n=17) and 43.2% (95% CI 27.3-68.2%) (n=25) for MRD-negative and MRD-positive patients, respectively (p=0.009). Conclusions: Induction chemotherapy followed by ASCT and either BC or BM was efficacious and tolerable, although BC was associated with more withdrawals for toxicity. PFS was not significantly different between BC and BM. The comparison between studies 50403 and 59909 with long-term follow up continues to suggest a PFS benefit from the addition of BC or BM among patients undergoing transplant. This did not translate into a PFS benefit from time of study enrollment possibly due to the higher pre-transplant dropout rate in 50403. MRD-negativity following induction chemo-immunotherapy is highly associated with improved PFS and the role of ASCT in post-induction MRD-negative patients is currently under investigation in a randomized clinical trial. Support: U10CA180821, U10CA180882, U24CA196171; ClinicalTrials.gov Identifier: NCT00310037 Disclosures Kaplan: Bayer Pharmaceuticals: Consultancy. Maurer:Celgene: Research Funding; Morphosys: Research Funding; Nanostring: Research Funding. Stock:Jazz Pharmaceuticals: Consultancy. Bartlett:Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Blum:Acerta: Consultancy; Astra-Zeneca: Consultancy. LaCasce:Seattle Genetics: Consultancy, Honoraria; Humanigen: Consultancy, Honoraria; Research to Practice: Speakers Bureau; Bristol-Myers Squibb: Other: Data safety and monitoring board. Leonard:AstraZeneca: Consultancy; Juno: Consultancy; BMS: Consultancy; ADC Therapeutics: Consultancy; Gilead: Consultancy; Biotest: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; United Therapeutics: Consultancy; Sutro: Consultancy; Genentech/Roche: Consultancy; Pfizer: Consultancy; Bayer: Consultancy. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy.

Abstract Abstract 94 Background: Lymphoma diagnosed during pregnancy is a rare occurrence. Further, there is heterogeneity in clinical presentation and a range of lymphoma histologies resulting in a continued deficiency of lymphoma-specific data in the literature regarding prognosis, optimal therapy, maternal complications, and fetal outcome. Methods: A comprehensive retrospective analysis was completed for patients (pts) diagnosed (dx) with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy at 9 large U.S. academic centers over a 13-year period (1998–2011). The vast majority of cases were co-managed with high-risk maternal fetal medicine. Data on maternal disease characteristics, treatment details, obstetric complications, and fetal outcomes were analyzed. Results: 88 cases were identified with complete data available in 82. The median age of pts was 31 yrs (18–40). Lymphoma dx occurred at a median of 24 weeks (wks) gestation (5–40). 15% of pts were dx during the 1st trimester, 46% during the 2nd trimester, 35% during the 3rd trimester, while 4% (n=3) of pts had a pre-existing NHL dx (follicular lymphoma (FL)). 52% (n=43) of pts had NHL and 48% (n=39) HL. Of NHL cases, 83% (n=33) were B-cell and 17% (n=10) T-cell. B-cell histologies were DLBCL n=23 (including 2 primary CNS and 1 'double hit' NHL), FL n=5 (including 1 leukemic phase FL), Burkitt's lymphoma n=3, and mixed histology n=1; T-cell histologies were anaplastic large cell n=6, PTCL not otherwise specified n=2, and T-cell/NK NHL n=2. Pts with B-cell NHL and HL were dx at a median age of 29 yrs (range, 18–40), while T-cell NHL pts were dx at a median of 34 years (19–37). MRI without gadolinium was the most common imaging modality utilized for staging. 63% of NHL and 19% of HL pts had stage III/IV disease (25% of HL with stage IIB). Pregnancy was terminated in 6 pts (n=4 aggressive NHL and n=2 HD) to enable immediate chemotherapy (five in the 1st trimester [at 5, 8, 10, 10, and 12 wks] and 1 pt in the early 2nd trimester who required high-dose methotrexate). 48 pts (63%) initiated anti-lymphoma therapy at a median of 25 wks gestation (range, 13–37) with 79% of pts initiating therapy in the 2nd trimester (see Table 1). The median gestation at time of lymphoma dx for pts who received intra-partum treatment was 20 wks vs 34 wks for pts who had therapy deferred to post-delivery (p<0.0001). The overall response rate among pts who received therapy was 87% (74% complete remission). Notably, gestation went to full-term in 54% with delivery occurring at a median of 37 wks (31–40). Therapy was deferred until post-delivery in 28 pts (37%) and the majority of these pregnancies were also carried to term (median delivery at 38 wks). At a median follow-up of 41 months (6–157), the 3-year PFS and OS for all pts were 79% and 89% respectively. Histology-specific 3-year PFS and OS were: B-cell NHL: 73% and 82%, respectively; T-cell NHL: 50% and 90%, respectively; and HL: 90% and 95%, respectively (Figure 1). Detailed obstetrical information was available in 59 pts. There were minimal pre-term complications, the most common being induction of labor in 45%. Perinatal events included spontaneous rupture of membranes in 5% and pre-eclampsia in 8%. Further, there were no differences in these events detected among pts who received intra-partum treatment vs deferred therapy. No episodes of chorioamnionitis or endometritis were noted. There was 1 stillbirth that occurred at 19 wks gestation in a 34-year-old pt with double-hit NHL following 1 cycle of R-CHOP. The median birth weight of infants was 2427 grams (1005–5262) with no difference among pts who received intra-partum chemotherapy vs not (2637 grams vs 2212 grams, respectively; p=NS). Microcephaly was reported in 1 case following 4 intra-partum cycles of CHOP for DLBCL; there were otherwise no malformations detected. Conclusions: To our knowledge, this represents one of the largest experiences reported of lymphoma in pregnancy. Our data show that standard NHL and HL chemotherapeutic regimens (without anti-metabolites) administered during the 2nd and 3rd trimester, including as early as 13 wks gestation in select cases, is associated with minimal maternal complications or fetal detriment. In addition, pts with low risk clinical scenarios (e.g., indolent NHL and/or late gestational dx) had therapy safely deferred to post-partum. In our experience, this approach was associated with overall expected lymphoma-related survival. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 728 Background: LM, an antibody-drug conjugate (ADC), is designed to specifically kill CD56+ cancer cells and contains a potent maytansinoid cytotoxic agent (DM1) attached to a CD56-targeting antibody. MM shows CD56 expression in >70% of cases. LM has demonstrated single agent clinical activity and an acceptable safety profile in relapsed/refractory (rel/ref) MM patients. Preclinical studies showed enhanced anti-MM activity when LM was combined with Len/Dex. To further study the safety and efficacy of LM in combination with Len/Dex, a phase I study was conducted in rel/ref patients. This abstract reports updated results on the safety and efficacy of LM/Len/Dex and preliminary results on the pharmacokinetics (PK) and immunogenicity studies. Methods: Primary study objectives were to determine the safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), anti-MM activity and PK of LM in combination with standard oral (PO) doses of Len (25 mg po, daily on days 1–21) and Dex (40 mg po on D 1, 8, 15, and 22) in CD56+ rel/ref MM patients who have received at least 1 prior therapy. LM was given intravenously (IV) on D 1, 8, and 15 on a 28-day cycle. Dose escalation was conducted in new cohorts of patients to define the MTD, which was then further evaluated in a dose-expansion cohort. Adverse events (AEs) were assessed using CTCAEv3 criteria, and dose-limiting toxicity (DLT) determination was based on the occurrence of AEs that were probably or definitely attributed to the study regimen. Efficacy was assessed using the International Myeloma Working Group (IMWG) criteria. Enrollment has completed and 16 patients remain on study. Results: Forty-four patients were enrolled, 41 are currently evaluable for safety and 32 are evaluable for efficacy. The median number of prior therapies was 2 (range 1–11), 62% of patients had prior Len exposure and 33% were Len refractory. LM doses of 75 (N = 11), 90 (N=4), and 112 (N =6) mg/m2 were evaluated in the dose-escalation phase. The most common AE was peripheral neuropathy (PN), which occurred more frequently at higher LM doses (55% at 75 mg/m2 and 100% at 90 and 112 mg/m2); Grade 3 PN was seen only in patients treated at 90 mg/m2 or above. PN emerged, in most cases, in cycles >3 and was manageable with LM dose modification. During dose escalation, 1 patient experienced Grade 4 neutropenia and hyperuricemia. The 75 mg/m2 LM dose was considered the MTD based on overall tolerability and the lower incidence of PN observed, and was further tested to determine its suitability as the RP2D in the dose expansion portion of the study (N=23 patients, 19 patients available for safety evaluation). Grade 1–2 PN occurred in 8 patients (42%) and grade 3 PN was observed only in 1 pt in the dose-expansion cohort. Two patients developed grade 3 tumor lysis syndrome (TLS). Other grade 3 AEs reported in 1 patient each (5%) in the dose-expansion cohort consisted of neutropenia, thrombocytopenia, anemia, hemolytic anemia, and LDH increase. Efficacy was observed across all dose levels and the overall response rate (ORR) was 59%, including 1 patient each with stringent complete response (sCR) and complete response (CR), 8 patients with very good partial remission (VGPR), and 9 patients with partial remission (PR). No immunogenicity against the antibody (HAHA) or DM1 component (HADA) of LM was detected. PK results from 18 patients treated at 75 mg/m2 indicate LM Cmax and exposure in this combination regimen is consistent with LM monotherapy. Conclusions: Based on all available safety data, 75 mg/m2 was considered the RP2D. LM at 75mg/m2 in combination with Len and Dex has shown objective evidence of clinical activity with an acceptable safety profile. Disclosures: Off Label Use: Lorvotusumab mertansine is not FDA approved for treatment of multiple myeloma alone or in combination with lenalidomide and dexamethasone as is investigated in this trial. Running:ImmunoGen, Inc.: Employment. Murphy:ImmunoGen, Inc.: Employment. Guild:ImmunoGen, Inc.: Employment. Carrigan:ImmunoGen, Inc: Employment. Ladd:ImmunoGen, Inc.: Employment. Wolf:ImmunoGen, Inc.: Employment, Equity Ownership. O'Leary:ImmunoGen, Inc.: Employment. Ailawadhi:Millenium Pharmaceuticals: Speakers Bureau.

Diffuse large B-cell lymphomas (DLBCLs) and follicular lymphoma (FL) are the most common subtypes of B-cell non-Hodgkin’s lymphomas in adults. Histologic transformation of FL to DLBCL (TFL) occurs in approximately 15% of patients and is generally associated with a poor clinical outcome. Phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promising results in the treatment of relapsed/refractory FL. CAR T-cell therapy (axicabtagene ciloleucel and tisagenlecleucel) has emerged as a novel treatment option for relapsed/refractory DLBCL and TFL. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines for B-Cell Lymphomas regarding the treatment of TFL and relapsed/refractory FL and DLBCL.

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.

Abstract Purpose: Randomized, multicenter, open-label, phase 2/3 trial investigating lenalidomide versus investigator's choice (IC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Experimental Design: Patients with DLBCL who received ≥2 prior therapies were stratified by DLBCL subtype [germinal center B-cell (GCB) vs. non-GCB; determined by immunohistochemistry (IHC)] and then randomized 1:1 to lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin). Crossover to lenalidomide was permitted for IC-treated patients with radiologically confirmed progressive disease. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival, and subtype analysis [GCB vs. activated B-cell (ABC)] using gene expression profiling (GEP) were exploratory endpoints. Results: Stage 1: 102 DLBCL patients (by IHC: non-GCB, n = 54; GCB, n = 48) received ≥1 dose of lenalidomide or IC. Hematologic treatment-emergent adverse events with lenalidomide versus IC included neutropenia (42.6%; 36.4%), anemia (33.3%; 47.3%), thrombocytopenia (24.1%; 43.6%), and leukopenia (5.6%; 12.7%), respectively. Overall, lenalidomide-treated patients had an ORR of 27.5% versus 11.8% in IC (ORRs were similar regardless of IHC-defined DLBCL subtype). Median PFS was increased in patients receiving lenalidomide (13.6 weeks) versus IC (7.9 weeks; P = 0.041), with greater improvements in non-GCB patients (15.1 vs. 7.1 weeks, respectively; P = 0.021) compared with GCB (10.1 vs. 9.0 weeks, respectively; P = 0.550). Conclusions: The clinical benefit of lenalidomide monotherapy in DLBCL patients was more evident in the non-GCB subtype. Exploratory analyses suggest that this preferential benefit was more pronounced in the GEP-defined ABC population, demonstrating a need for additional studies of lenalidomide in DLBCL using GEP subtyping. Clin Cancer Res; 23(15); 4127–37. ©2017 AACR.