ALBERT

Description: The phase II CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective, B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC-positive). Eligible patients ≥18 years with previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2-5. Venetoclax 800 mg (days 4-10, cycle 1 and days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and CHOP (6-8 cycles); 21-day cycles. Primary endpoints: safety, tolerability, and complete response (CR) at end of treatment (EOT). Secondary endpoints: progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC-positive subgroups. With median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (Hazard ratio [HR] = 0.61, 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC-positive subgroups (HR = 0.55, 95% CI, 0.34-0.89), versus R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI versus GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased but manageable myelosuppression and the potential of improved efficacy particularly in high-risk, Bcl-2 IHC-positive patient subgroups.

Description: Introduction: Idelalisib (IDELA) is a selective, small molecule inhibitor of PI3Kd that has shown significant efficacy in treatment of patients (pts) with relapsed chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). A common adverse event (AE) observed in IDELA studies is diarrhea/colitis (DC): grade ≥3 ~15%. Published preclinical data suggests that PI3Kd plays a critical role in regulating the function and development of regulatory T-cells (T-regs). This biomarker analysis aimed to evaluate possible immune mechanisms that may have contributed to DC in IDELA-treated pts. Methods: Longitudinal absolute peripheral blood T (CD4+ and CD8+), NK (CD16+/CD56+) cell subsets, cytokines, and chemokine levels from patients treated with IDELA were analyzed (Table 1). Since absolute numbers of T-reg cells were not available, we utilized epigenetic qPCR method (Kleen T. et. al. J Immunother Cancer 2015) to assess the status of T-regs by quantifying FOXP3 utilizing banked peripheral blood mononuclear cells (PBMCs). The following cytokines and chemokines were measured: IL-12p40, IL-17A, IFNγ, TNFα, G- CSF, MIP1α (CCL3), CCL5 (RANTES), IL-10, IL-1RA, IL-6, IL-7, IL-8, IL-15, CRP, and IP-10 (CXCL10). We evaluated the association of changes from baseline of these biomarker(s) with the occurrence and severity of DC events during IDELA treatment. Association of cytomegalovirus (CMV) with DC was not addressed in this study and is being presented separately. Results: There were no differences in absolute numbers of T (CD4+ or CD8+) and NK cells between pts treated with IDELA in both trials with grade ≥3 DC vs those with no DC. Consistently, results from epigenetic qPCR analysis also demonstrated no differences in temporal profiles for peripheral T-cell subsets (CD3+, CD8+, or FOXP3+) in CLL pts treated with IDELA with grade ≥3 DC vs no DC. Baseline and on-treatment changes in peripheral T-cell subsets were not predictive of DC. Analysis of T-cell subsets from the visit immediately prior (t-1) to the first occurrence of grade ≥3 DC was not predictive, and revealed no differences compared to pts with no DC. Lower levels of CD3+, CD8+, and FOXP3+ were noted longitudinally as well as at t-1 visits in grade 1/2 DC vs non-DC pts, but these changes were not predictive of grade 1/2 DC. Increased levels of circulating pro-inflammatory cytokines (IL-15, IFN-γ, and CLL5) were noted in both CLL and indolent non-Hodgkin lymphoma (iNHL) pts treated with IDELA. IL-17A level was significantly higher at the t-1 visit in CLL pts with grade ≥3 DC vs no DC. However, Receiver Operating Characteristic analysis deemed that neither individual cytokine/chemokine or in combination was not predictive for DC occurrence. CLL/iNHL pts with grade ≥3 DC vs no DC were noted to have higher on treatment IL-8. CLL pts presented lower baseline IL-6 and G-CSF levels in patients with grade ≥3 DC vs no DC (Table 2). There were no associations between baseline circulating plasma markers and DC in pts with iNHL. Conclusion: With currently available data, no single circulating immune biomarker is associated with or is predictive for the development of DC during treatment with IDELA. Lower levels of CD3+, CD8+, and FOXP3+ were noted longitudinally in grade 1/2 DC vs no DC pts. No differences were observed in temporal profiles for T-cell subsets in pts with grade ≥3 DC vs those with no DC. However, higher on-treatment IL-8 and lower baseline IL-6 and G-CSF were noted in the relapsed CLL pts with grade ≥3 DC when compared with no DC pts. While quantitative analysis of these T-cell subsets was not associated with grade ≥3 DC, the qualitative function of T-cells may play a role in mediating DC. Functional assays for T-cells were not explored in this study. In addition, our concurrent analysis of colonic biopsies and association with CMV in pts with IDELA associated DC will be presented separately. Disclosures Furman: Pharmacyclics: Consultancy, Speakers Bureau; Gilead Sciences: Consultancy; Janssen: Consultancy; Genentech: Consultancy; Abbvie: Consultancy, Honoraria. Hallek:Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau. Sharman:Gilead Sciences, Inc.: Honoraria, Research Funding. Hillmen:Pharmacyclics: Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Abbvie: Research Funding. Zelenetz:Gilead Sciences: Research Funding. Flinn:Janssen: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Gilead Sciences: Research Funding; ARIAD: Research Funding; RainTree Oncology Services: Equity Ownership. Jurczak:Gilead Sciences: Research Funding; Janssen: Research Funding; Celltrion, Inc: Research Funding; Acerta: Research Funding; Bayer: Research Funding. Munugalavadla:Gilead Sciences: Employment, Equity Ownership. Xiao:Gilead Sciences: Employment, Equity Ownership. Zheng:Gilead Sciences: Employment, Equity Ownership. Rao:Gilead Sciences: Employment, Equity Ownership. Dreiling:Gilead Sciences: Employment, Equity Ownership. Salles:Roche/Genentech: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Gilead: Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Mundipharma: Honoraria. O'Brien:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria.

Description: Introduction: Venetoclax (VEN) based therapy has become a standard of care in front line and relapsed-refractory (R/R) CLL based on favorable efficacy and toxicity. Whereas prospective data regarding activity of therapies following ibrutinib (IBR) or idelalisib (IDE) are available in the settings of progression (VEN, non-covalent BTKi) and intolerance (acalabrutinib), how best to manage patients (pts) who discontinue (dc) VEN remains a key unanswered question. With the increased use of VEN in early lines of therapy (LOT; CLL 14, MURANO), the activity of BTK inhibitors (BTKi) and cellular therapies following VEN becomes a critical issue. No prospective study has addressed this question, and currently reported VEN clinical trials have limited information about subsequent treatments. While recent data describe VEN resistance mechanisms (Guieze 2018, Blombery 2019), the impact of VEN resistance on efficacy of post VEN therapies is unknown. To address this gap, we conducted an international study to identify a large cohort of pts who dc VEN and have been subsequently treated. Methods: We conducted an IRB approved multicenter (31 US, EU, South American sites, in partnership with UK CLL Forum and CORE registry), retrospective cohort study of CLL pts who dc VEN for any reason. We examined demographics, dc reasons, responses, survival, adverse events (AEs) and activity of post VEN therapies. Primary endpoints were overall response rate (ORR) and progression free survival (PFS) for the post VEN treatments stratified by treatment type (BTKi, PI3Ki and cellular therapy: CAR-T or alloHSCT). ORR was defined by iwCLL criteria and PFS was defined from VEN dc to disease progression (PD), death, or last follow up for next treatment. Pts were further stratified by BTKi (resistant / intolerant) and PI3Ki exposure prior to VEN. PFS-2 was defined as time from VEN start to tumor progression on IBR or death from any cause. Results: 326 CLL pts who dc VEN in the front line (4%) and R/R settings (96%) were identified. The cohort was 69% male, 87% white, median (med) age 66 (38-91) at VEN start, 27% treated with VEN based combinations (n=88, med 6 cycles anti-CD20 abs). Pre VEN prognostic features: 82% IGHV unmutated (n tested=166), 47% del17p (n=306), 45% TP53 mut (n=217), 39% complex karyotype (n=273), 23% BTK mut (n=79), 18% NOTCH1 mut (n=103), 10% PLCγ2 mut (n=74). Pts received med 3 therapies (0-11) prior to VEN; 40% were BTKi naïve (n=130), 60% were BTKi exposed (196) and 81% were IDE naïve (n=263). Most common reasons for VEN dc were PD (38%), AE (20%), Richter's transformation (RT, 14%), 8% pt preference, and HSCT 5%. Of 326 pts who dc VEN, 188 (58%) were treated with a subsequent LOT, 61 are alive and untreated and 77 died prior to a subsequent LOT. Post VEN sequencing analyses focused on BTKi, PI3Ki and cellular therapy (CAR-T or alloHSCT) activities following VEN dc (Table1). ORR to BTKi was 84% (n=44) vs. 54% (n=30, p

Description: Background: NHL is a disease of older adults and henceforth the oncology community will be increasingly confronted with the challenges of the older lymphoma patient (pt). Phase II data demonstrates dose-adjusted (DA)-EPOCH +/- rituximab is efficacious in high grade and aggressive NHL (J Clin Oncol. 2008 Jun 1;26(16): 2717-24). Additionally, infusional doxorubicin may confer greater safety in elderly pts compared with bolus delivery. A Phase III trial (NCT00118209) comparing DA-R-EPOCH and R-CHOP has been completed, but the results are not currently available. To date, there is limited data on efficacy and safety in elderly patients treated with DA-R-EPOCH. We explored our single center experience to inform therapeutic choices in older adults. Methods: We retrospectively reviewed all pts treated with EPOCH at MSKCC from 2003 to 2014, identifying 181 pts in total, of which 54 pts 〉 60 yrs (out of 73 pts 〉60 yr) received DA-EPOCH at initial diagnosis. Data was available regarding their baseline characteristics, dose adjustments/treatment modifications, hospitalizations, and disease related outcomes for all pts. Outcome measures included progression free (PFS) and overall survival (OS), hospitalizations, and dose adjustments. Results: Of 54 patients, histologies included DLBCL (n=42, 78%), T-cell lymphoma (n=8, 15%), and Burkitt lymphoma (BL) (n=4, 7%). The median age of all patients was 70.5 yrs (range 61-93 yrs), with 54% female. Prior malignancy was present in 31% and baseline LVEF was 〉55% in 98% of pts. For DLBCL patients (n=42): median age 72 yrs (61-92 yr), M:F 24:18, Stage I/II v. III/IV: 21% v. 79%, aaIPI 0-1 v. 2-3: 24% v 76%; cell of origin (Hans) GC/ABC/unknown: 43%/52%/5%. Ki67%: median 90% (range 20-100%). T-cell pts (n=8): median age 68 yrs (61-75 yr), female 50%, histology ATLL(n=4), PTCL (n=3), ALCL ALK- (n=1); 100% adv. stage; BL pts (n=4): ages 65, 69, 82, 81 yrs, 1 early stage, 3 adv. stage, 1 low risk, 3 high risk. Rituximab was given in 96% of b-cell NHL. Peg-GCSF/GCSF was used with each cycle of EPOCH. A full 6 cycles of EPOCH was completed 52% of the time and dose adjusted in 66% of pts with a median of 4 adjusted cycles/pt (range 1-6). Dose increases occurred in 30% of pts, dose decreases 26%; 11% of pts started at dose level -1. Safety: Cardiac events occurred in 22% of pts, with 2 pts experiencing anthracycline induced cardiomyopathy/CHF, the remainder included G ≥3 arrhythmias (n=6) or chest pain/angina (n=4) without change in EF. Hospitalization for G≥3 toxicity occurred in 68.5% (n=37) of pts (41% more than once): neutropenic fever/infection (n=19/9), AKI/dehydration (n=7), syncope (n=2); Treatment related mortality was 4% (n=2). Outcomes: With a median followup of 1.5 yrs, 33 of 54 pts remain progression free (DLBCL 30/42, TCL 1/8, BL 2/4, p=0.007). For all pts, median PFS and OS have not been reached: PFS and OS at 1.5 yr is 57% and 66%, respectively. For DLBCL pts, median PFS and OS is not reached: PFS and OS at 1.5 yr is 69% and 78%, respectively. In log-rank analysis: aaIPI (p=.15), Stage (p=.08) and cell of origin (p=.35) did not predict OS; aaIPI (p=.05) and stage (p=.04) predicted PFS, but cell of origin was not significant. There was no significant difference in outcome based on dose adjustments. Conclusions: DA-EPOCH +/- R is an effective treatment option for pts 〉 60 yrs with advanced stage, high risk DLBCL; Hospitalizations for toxicity were frequent, but TRM was low. Cardiomyopathy was infrequent. Dedicated efforts to explore initial dose-reductions and optimal number of cycles in this older pt population would be beneficial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background: Recent reports from prospective clinical trials of R-containing chemotherapy in DLBCL patients suggest that gender, weight and/or BMI influence clinical outcomes. Pharmacokinetic studies by the German High Grade Lymphoma Study Group have shown that R clearance is relatively slow in elderly women compared to men, leading to higher levels and prolonged exposure and hence better clinical outcomes in elderly females. Specifically, it has been suggested that elderly men are underdosed, based on faster R clearance (Muller et al., 2012; Pfreundschuh et al., 2014). Regarding BMI as a predictor of clinical outcome, analysis of the US Veterans Administrative database showed an association between increased BMI and improved survival in DLBCL patients (Carson et al., 2012), while the ECOG clinical trial (E4494) for elderly DLBCL patients failed to reveal a significant association of BMI with clinical outcomes, or a gender difference related to BMI in failure-free survival (Hong et al., 2014). To further investigate these associations, we studied the effect of gender, BMI as well as body surface area (BSA, the actual dosing parameter), and potential interactions among these factors on long-term clinical outcomes for elderly DLBCL patients in the National Comprehensive Cancer Network (NCCN) non-Hodgkin lymphoma database. Methods: De novo DLBCL patients with age 〉 60 yrs. were identified from the NCCN adult DLBCL cohort. Patients were diagnosed between June 2000 and December 2010. All received R as part of first-line therapy. Outcomes evaluated included progression free survival (PFS) and overall survival (OS) at 3 years based on patient gender, age and BMI/ BSA at presentation. Gender was stratified based on BMI (18.5-25, 〉25) or BSA (2), and Kaplan-Meier estimates were calculated. Associations with disease progression and survival were additionally adjusted for the International Prognostic Index (IPI) in the multivariable Cox regression analyses. Results: Of the 1,386 DLBCL patients who received R, 627 were elderly with age 〉60 yrs. The majority of elderly men were either overweight or large: only 13% had BMI

Description: Background: PI3Kδ signaling is at the crossroads of B-cell receptor signaling pathways that are major drivers of survival and proliferation of B-cell malignancies, making it an attractive target for drug development. PI3Kδ inhibitors have proven clinical efficacy in relapsed or refractory non-Hodgkin's lymphoma (NHL); however, the high incidence of immune-related adverse events (irAEs) of early generation PI3Kδ inhibitors has limited their use. Management of toxicities by daily dose reduction may reduce the incidence of toxicities but also can lead to potential loss of efficacy, therefore novel approaches are needed to maximize clinical utility. ME-401 is an oral once-daily selective PI3Kδ with a molecular structure and pharmacodynamic characteristics that are distinct from other PI3Kδ inhibitors, either approved or under development. ME-401's high volume of distribution, long half-life (~30 hours), and intracellular penetration/ retention kinetics predict a significantly higher tumor exposure to drug relative to plasma which has been borne out in pre-clinical mouse lymphoma studies. These properties allow use of an intermittent dosing schedule to minimize immune-related toxicities common to other PI3kδ agents. ME-401 has demonstrated high and objective response rates (ORR) in both FL and CLL/SLL; 80% in 50 patients with relapsed/refractory (R/R) FL and 100% in 14 patients with R/R CLL/SLL (Zelenetz et al 2019). During the Phase 1b dose escalation study of ME-401 administered on a continuous daily dosing schedule (CS, 28-day cycle), no dose limiting toxicities were identified, and the first dose level of 60 mg was selected for further development due to its high response rate. Delayed (≥ cycle 3) grade 3 AEs such as diarrhea and rash occurred in approximately one third of patients (Zelenetz, 2018). These AEs are likely related to on-target effects on T-regulatory cells (T-regs) resulting in immune-mediated toxicity. With the goal of improving tolerability we developed a novel dosing approach for ME-401, reducing dose intensity via intermittent dosing (IS) 7 days on/21 days off, with the goal of allowing Treg repopulation. The IS is introduced after an initial period (2 cycles) of daily dosing for tumor debulking. Preliminary evaluation of this novel schedule resulted in a marked decrease in delayed Grade 3 irAEs compared to the CS. The ME-401-003 (TIDAL) study was designed to further evaluate risk-benefit profiles of these two treatment schedules of this potent PI3Kδ inhibitor in patients with relapsed or refractory FL. Study Design and Methods:ME-401-003 (TIDAL) is a global study of ME-401 in patients with FL after failure of ≥2 prior systemic therapies and will enroll approximately 166 subjects. Subjects must have received prior therapy with an anti-CD20 antibody and chemotherapy with an alkylating agent or purine analogue with adequate organ and bone marrow function; no prior therapy with a PI3Kδ is allowed. Upon meeting eligibility criteria, patients are randomized to the CS or IS dosing group with a 1:1 allocation ratio at baseline and receive open-label ME-401 at 60 mg daily for the first two cycles. The stratification factors for randomization are disease status (relapsed or refractory) and tumor bulk. Patients with stable disease or an objective response after 2 cycles will then continue onto the blinded, placebo-controlled portion of the study and will receive ME-401 either on a CS or an IS. Patients who experience disease progression on IS will be able to receive open-label ME-401 on CS to explore the recapture of response. Subjects who develop grade ≥ 2 adverse of special interest (AESI) will have study drug halted and upon resolution of AE will continue on open label IS to mitigate toxicity. The primary objectives are ORR using Lugano Response Criteria, as determined by an Independent Response Review Committee, and tolerability defined as the rate of AEs requiring dose modification or study drug discontinuation utilizing a sample size of 75 subjects per treatment schedule. A correlative study will evaluate the effects of ME-401 on T-cell subsets, cytokines and chemokines. The study opened to enrollment in December 2018 with sites planned in North America, Europe, Asia, New Zealand and Australia. (NCT03768505) Disclosures Zelenetz: Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: 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; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: 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; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zinzani:VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GILEAD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; JANSSEN-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Consultancy. Buske:Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding; Roche: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; Bayer: Research Funding; Celltrion: Honoraria, Speakers Bureau; Hexal: Honoraria, Speakers Bureau. Ribrag:AZ: Membership on an entity's Board of Directors or advisory committees; argenX: Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Cunningham:Bayer: Research Funding; Amgen: Research Funding; MedImmune: Research Funding; Clovis: Research Funding; Merck: Research Funding; 4SC: Research Funding; Eli Lilly: Research Funding; Merrimack: Research Funding; AstraZeneca: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Janssen: Research Funding. Jurczak:Gilead: Research Funding; Takeda: Research Funding; Celtrion: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Research Funding; Incyte: Research Funding; Celgene Corporation: Research Funding; TG Therapeutics: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Novo Nordisk: Research Funding; Roche: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding. Abrisqueta:Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau. Brown:Kite, a Gilead Company: Consultancy, Research Funding; Pharmacyclics: Consultancy; Pfizer: Consultancy; Juno/Celgene: Consultancy; BeiGene: Consultancy; Loxo: Consultancy, Research Funding; Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Catapult Therapeutics: Consultancy; Dynamo Therapeutics: Consultancy; AstraZeneca: Consultancy; Novartis: Consultancy; Octapharma: Consultancy; Invectys: Other: Data safety monitoring board; Morphosys: Other: Data safety monitoring board; Teva: Honoraria; Janssen: Honoraria; Sun Pharmaceuticals: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy; Sunesis: Consultancy; Acerta Pharma: Consultancy; AbbVie: Consultancy.

Description: Background Disease characteristics, treatment patterns, and outcomes of follicular lymphoma (FL) patients (pts) aged 〉80 years (yrs) are infrequently reported. Further, the original Follicular Lymphoma International Prognostic Index (FLIPI) has not been formally studied in pts aged 〉80 yrs. Also, whether FLIPI is associated with overall survival (OS) in pts aged 〉80 yrs is unknown. Patients/Methods We used the National LymphoCare Study—a Genentech-sponsored, prospective, multicenter registry of FL pts across the United States without study-specific treatment—to comprehensively analyze FL pts aged 〉80 yrs. Using Pearson chi-squared tests, associations of age groups with disease characteristics and overall response rate (ORR) were examined. Median progression-free survival (PFS) and OS by treatment regimen were estimated using the Kaplan-Meier method. Cox proportional hazards regression that were adjusted for baseline disease factors were used to assess treatment differences in PFS, lymphoma-related mortality (LRM, which includes both disease and treatment-related deaths), and OS, as well as the significance of age by treatment interactions. FLIPI and a prognostic model that was constructed based on the findings were used to predict outcomes. Results Of 2649 evaluable pts, 209 (8%) were aged 〉80 yrs. Compared with pts aged ≤60, pts aged 〉80 yrs were more likely to be Caucasian, to have worse performance status, to have lower hemoglobin (Hgb) value (80 yrs had lower ORR compared with younger pts and were less likely to receive rituximab + chemotherapy (P 80 yrs when rituximab + chemotherapy induction was administered (44% for pts aged ≤60, 59% for pts aged 〉80, P=.04). After adjusting for maintenance use, sex, and baseline factors, age significantly differentiated PFS impact of observation, rituximab monotherapy, and rituximab + chemotherapy (P=.01). No treatment regimen provided superior PFS or OS in pts aged 〉80 yrs. With a median follow-up of 6.5 yrs for all pts (4.3 yrs for pts aged 〉80 yrs), 5-year OS was 59% and 92%for patients aged 〉80 and ≤60 yrs, respectively. OS in pts aged 〉80 yrs varied based on FLIPI score (log-rank test, P=.01; Figure 1). Interestingly, the percentage of deaths that were disease-related was 40% in pts aged 〉80 yrs, which was comparable to the percentage in pts aged ≤60 yrs of 48%. Cox modeling showed that lower Hgb, B symptoms, and male sex predicted worse OS (P80 yrs. Recognizing that males have inferior OS compared with females in the general population, we constructed a prognostic model composed only of B symptoms and Hgb level 80 yrs and so was a proposed prognostic model comprising lower Hgb and B symptoms. Independent validation of this model is required, and additional prospective studies that are designed for the oldest old are warranted. Disclosures: Nabhan: Genentech Inc.: Advisory Board Other, Honoraria. Byrtek:Genentech, a member of the Roche group: Employment, Equity Ownership; Roche: Equity Ownership, stock options, stock options Other. Dawson:Genentech: Employment; Roche: Equity Ownership. Link:Genentech: Consultancy; Millenium: Consultancy; Pharmacyclics: Consultancy; Spectrum: Consultancy; Genentech: Research Funding; Millenium: Research Funding; Pharacyclics: Research Funding. Zelenetz:GSK: Consultancy; Celgene: Consultancy; Cephalon: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; Sanofi-Aventis: Consultancy; Genentech: Research Funding; GSK: Research Funding; Roche: Research Funding; Cancer Genetics: Scientific Advisor Other. Cerhan:Genentech: Scientific Advisory Board of the National LymphoCare Study Other. Flowers:Abbott, Celgene, Millennium/Takeda, Sanofi, Spectrum, Janssen: Research Funding; Celgene, Genentech Bio-oncology: Consultancy.

Description: Introduction: Optimal management of mantle cell lymphoma (MCL) remains undefined. However, recent data support the conclusion that upfront consolidation with high dose therapy with autologous stem cell rescue (HDT/ASCR) can improve the PFS (Dreyling, et al., 2005; Geisler, et al., 2008) and possibly OS (Geisler, et al. 2008). Based on gene expression profiling data, the proliferation signature has emerged as a critical determinant of prognosis in MCL (Rosenwald, et al., 2003). Immunohistochemical assessment of proliferation as estimated by MIB-1 (Ki-67) staining has been shown to predict outcome in patients with MCL treated with chemotherapy or immunochemotherapy. With conventional chemotherapy, the reported MIB-1 staining cutoff associated with poor prognosis reportedly varies from 10–30%. Since 1994 we have treated patients (pts) with MCL with sequential chemotherapy followed by HDT/ASCR. The current analysis is a retrospective review of our treatment program focused on the impact of upfront consolidation with HDT/ASCR on the prognostic significance of proliferation as measured by MIB-1 immunohistochemistry. Methods: Seventy-nine patients underwent upfront consolidation with HDT/ASCR for MCL. Fifty-two patients had evaluation of proliferation by MIB-1 immunohistochemistry. MIB-1 expression was estimated visually and assigned a percentage. Patients were binned into quintiles of MIB-1 expression: 0–20% (n=32, 61.5%); 21–40% (n=5, 9.6%); 41–60% (n=5, 9.6%); 61–80% (n=5, 9.6%); and 81–100% (n=5, 9.6%). Outcomes were analyzed by the method of Kaplan-Meier and comparisons were by log-rank. Results: The EFS and OS at 5 years was 65.1% and 61.4% respectively for the subset of patients with available MIB-1 staining (n=52); the outcomes for the entire group (n=79) did not differ from the subset. Outcomes (PFS, OS) were evaluated by MIB-1 quintile with successive cutoff values of 20%, 40%, 60% and 80%. MIB-1 cutoff values of 40% or less were not predictive of outcome. However, when the cutoff was 60% or 80%, both the PFS and OS were significantly worse for the high proliferation group. Nineteen percent of patients had a proliferation fraction of greater than 60%. For patients with MIB-1 staining of 〉60% the PFS was 4.2 years and was not reached for the group with staining ≤60% (p=0.004). Similarly, overall survival was significantly different, (p=0.031). Conclusions: These findings suggest that upfront consolidation with HDT/ASCR can partially overcome the adverse impact of proliferation on outcome and the adverse outcomes are seen in a subgroup of approximately 20% of patients with MIB-1 staining of greater than 60%.

Description: Introduction: Cytarabine-containing induction chemotherapy followed by high dose therapy and autologous stem cell transplant (ASCT) is currently a standard treatment approach for younger patients with mantle cell lymphoma (MCL). This approach, however, may be associated with lesser efficacy in patients with high-risk disease biology (i.e. with elevated proliferative index, blastic morphology, or TP53 alteration). Older patients are treated with rituximab-based chemotherapy regimens without stem cell transplant. In this single-center prospective phase II study, we treated MCL patients, irrespective of their age, with immunochemotherapy combined with lenalidomide without ASCT to evaluate the safety and efficacy of this regimen. Methods: Treatment consisted of 3 parts: A) 4 cycles of lenalidomide (15mg orally days 1-14) and standard RCHOP chemotherapy in a 21-day cycle B) rituximab and high-dose cytarabine (RHIDAC) administered at a dose of 1,000-3,000 mg/m2 every 12 hours x 4 doses for a total of 2 cycles C) rituximab plus lenalidomide maintenance for 6 months. Eligible patients were untreated MCL, stage II-IV, KPS≥70%, and with adequate organ function. We enriched study enrollment for high risk patients, 31 of a total 47 patients, as defined by Ki-67 ≥30% and/or blastic/blastoid/pleomorphic morphologic subtype. PET/CT after each phase of treatment was completed and interpreted with the 5-point Deauville scale (negative=1-3). The primary endpoint of the study was to evaluate the 3-year progression free survival. Herein we are presenting preliminary data on the end-of-treatment (EOT) response rate and the toxicity of the regimen, including the interim and EOT PET data. Results: Interim data (as of June 1, 2018) for the first 45 of a planned 47 patients are presented here. Median age was 63 (range 30-79); 82% stage IV; MIPI low, intermediate and high risk were 31%, 31%, and 38%, respectively; 64% of patients had high-risk disease per our definition (28 patients with a Ki-67 ≥30% and 6 patients with blastic morphology). Of the 39 patients who completed Len-RCHOP induction, 85% were PET-negative and after RHIDAC, 95% of patients achieved a negative PET scan (Figure 1). Of the 26 patients who have completed Len-R maintenance, 92% were PET-negative, 8% PET-positive (Table 1). At EOT, 24 patients (92%) achieved a complete remission, 1 patient achieved a partial response, and 1 patient had progressive disease. Among the 24 patients who achieved a CR, the median follow-up is 9 months. Two relapses have occurred at 18 months and 25 months. The patients with a treatment failure (one PR at EOT, one progressive disease at EOT, and 2 relapses), occurred in patients either with a TP53 mutation (3/3 tested, 1 pending) or blastic morphology (3/4 patients). Overall the treatment program was well-tolerated and predominantly hematologic toxicities were observed, particularly during the RHIDAC phase consistent with past experience with this treatment regimen in MCL. During each phase (Len-RCHOP, RHIDAC, and Len-R maintenance), grade 3/4 neutropenia was observed at a rate of 13%, 52%, 16%, respectively; febrile neutropenia 1%, 4%, 0%, respectively; grade 3/4 anemia 11%, 32%, 1%, respectively; and grade 3/4 thrombocytopenia 8%, 75%, 2%, respectively. Comparing to our historical data in a cohort of 23 MCL patients (57% low risk), Len-RCHOP resulted in a higher PET-negative rate compared to RCHOP alone, 85% versus 65%, respectively. Conclusion: The addition of lenalidomide to RCHOP chemotherapy appeared to increase the rate of PET-negativity compared to historical results with RCHOP alone. Toxicity occurred as expected and was manageable. Early failures were observed in patients with TP53 mutation or blastic morphology. Although follow-up is limited, early results with this approach are promising. Disclosures Kumar: Seattle Genetics: Research Funding; Abbvie Pharmaceuticals: Research Funding; Adaptive Biotechnologies: Research Funding; Pharmacyclics: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Zelenetz:Novartis/Sandoz: Consultancy; Amgen: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; Abbvie: Research Funding; Gilead: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding. Hamlin:Portola: Consultancy. Matasar:Seattle Genetics: Honoraria. Moskowitz:Bristol Myers-Squibb: Consultancy, Research Funding; Takeda: Honoraria; Merck: Research Funding; Incyte: Research Funding; ADC Therapeutics: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Straus:Bayer: Consultancy; Medical Crossfire: Speakers Bureau; DAVA Oncology: Consultancy, Honoraria; JUNO: Consultancy; Millenium (Takeda): Consultancy, Research Funding; Seattle Genetics: Consultancy; Onco Tracker: Consultancy; Roch China: Speakers Bureau; InPractice Elselvier: Consultancy; Memorial Sloan Kettering Cancer Center: Employment. Younes:BMS: Honoraria, Research Funding; Astra Zeneca: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Roche: Honoraria, Research Funding; Novartis: Research Funding; Janssen: Honoraria, Research Funding; Merck: Honoraria; J&J: Research Funding; Curis: Research Funding; Incyte: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Seattle Genetics: Honoraria.

Description: Background/methods: Identifying relapsed or refractory (RR) classical Hodgkin lymphoma (cHL) patients (pts) eligible for lower-intensity second-line therapy (SLT) will aid in improving short-term and long-term treatment-related toxicity. We conducted a phase II study evaluating PET-adapted SLT with single-agent brentuximab vedotin (BV) followed by augICE (augmented ifosfamide, carboplatin, etoposide) for BV-naïve patients with RR cHL (Lancet Oncology 2015). In this study, patients who failed 1 line of therapy for cHL were treated with 2 or 3 cycles of BV, 1.2mg/Kg, administered weekly, 3 weeks on and 1 week off. Those who achieved PET-normalization proceeded directly to consolidation with autologous stem cell transplantation (ASCT). Those with persistent abnormalities on PET received 2 cycles of augICE prior to consideration for ASCT. At 3-year follow-up, outcomes for patients who achieved PET-normalization following BV alone or BV followed by augICE were identical. Furthermore, baseline metabolic tumor volume (bMTV) predicted outcome and improved the prognostic significance of pre-ASCT PET (Blood 2017). We now report 6-year follow-up from this study evaluating PET-adapted SLT with BV and augICE. Results: 65 pts enrolled onto this protocol, of whom 18 achieved PET-normalization (Deauville ≤ 2) after single-agent BV. These 18 pts included 8 (44%) with primary refractory disease, 7 (39%) with advanced stage disease, and 8 (44%) with extranodal disease. 17 of the 18 pts proceeded directly to ASCT and 1 pt experienced delay resulting in disease progression. That individual achieved PET-normalization following additional salvage chemotherapy (gemcitabine/vinorelbine/liposomal doxorubicin) and proceeded to ASCT. Of the other 47 pts who remained PET-positive after single-agent BV, 35 achieved PET-normalization after augICE, 9 remained PET-positive after augICE, 2 received no additional treatment before proceeding to ASCT (1 pt with Deauville 3 response to BV, 1 with Deauville 4 response), and 1 pt withdrew consent and was lost to follow-up. 64 of 65 pts proceeded to transplant and median post-ASCT follow-up is 5.98 yrs (range 4.4-7.2 yrs). 6-yr overall survival is 86%, 6-yr progression free survival (PFS) is 73%, and 6-yr time to tumor progression (TTP) is 78%. Overall, there have been 8 deaths, which were due to disease progression (n=5), progressive multifocal leukencephalopathy (PML) (n=1), treatment-related respiratory failure (n=1), and myelodysplastic syndrome (MDS) (n=1). Pts who proceeded to ASCT following single-agent BV achieved durable remission with 6-year TTP of 80%. Outcomes for the BV-only group were similar to those who required BV and augICE to become PET-negative (6-yr TTP 82%) and were more favorable than for those who remained PET-positive after BV and augICE (6-yr TTP 56%, p=0.058) (Figure 1). With 6-yr follow-up, bMTV 〉 109.5 cm3remained prognostic for the entire group and aided in predicting which pts ultimately developed disease progression. In particular, among the pts who achieved PET-normalization with BV alone prior to ASCT, 6-yr TTP was 92% vs 40% for low and high bMTV respectively, p=0.017 (Figure 2). Similarly, for pts who achieved PET-normalization following BV and augICE, 6-yr TTP was 85% vs 33% for low and high bMTV respectively, p=0.002. Conclusions: For pts with RR cHL, long-term remission can be achieved following lower-intensity SLT with single-agent BV followed by ASCT, provided PET-normalization is achieved after single-agent BV. bMTV identifies which pts within this favorable group are likely to develop disease progression and therefore treatment strategies using bMTV to direct intensity of therapy should be explored. Disclosures Moskowitz: Erytech Pharma: Consultancy; Incyte: Research Funding; Cell Medica: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Erytech Pharma: Consultancy; Merck: Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Erytech Pharma: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Erytech Pharma: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Merck: Research Funding; Cell Medica: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Erytech Pharma: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Cell Medica: Consultancy; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Erytech Pharma: Consultancy; Incyte: Research Funding; Cell Medica: Consultancy; Incyte: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy. Horwitz:Seattle Genetics: Consultancy, Research Funding; Forty-Seven: Research Funding; Trillium: Research Funding; Miragen: Consultancy; Portola: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Affimed: Consultancy; Innate Pharma: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy; Trillium: Research Funding; Portola: Consultancy; Aileron: Research Funding; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Affimed: Consultancy; Mundipharma: Consultancy; Aileron: Research Funding; Forty-Seven: Research Funding; ADCT Therapeutics: Research Funding; Miragen: Consultancy; ADCT Therapeutics: Research Funding; Kyowa Hakko Kirin: Consultancy; ADCT Therapeutics: Research Funding; Astex: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin: Consultancy; Astex: Consultancy; Affimed: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Miragen: Consultancy; Kyowa Hakko Kirin: Consultancy; Miragen: Consultancy; Mundipharma: Consultancy; Aileron: Research Funding; ADCT Therapeutics: Research Funding; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Astex: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Consultancy; Celgene: Consultancy, Research Funding; Forty-Seven: Research Funding; Astex: Consultancy; Portola: Consultancy; Seattle Genetics: Consultancy, Research Funding; Kura: Consultancy; Aileron: Research Funding; Kyowa Hakko Kirin: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Trillium: Research Funding; Innate Pharma: Consultancy; Trillium: Research Funding; Kura: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Forty-Seven: Research Funding; Portola: Consultancy; Kura: Consultancy; Affimed: Consultancy; Kura: Consultancy; Celgene: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding. Kumar:Seattle Genetics: Research Funding. Matasar:Genentech, Inc.: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding; Bayer: Consultancy, Honoraria, Other; Roche: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding; Merck: Consultancy, Equity Ownership; Juno Therapeutics: Consultancy; Teva: Consultancy; Rocket Medical: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, accomodation, expenses, Research Funding; Daiichi Sankyo: Consultancy; GlaxoSmithKline: Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Other: Travel, accommodation, expenses. Noy:Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Janssen: Consultancy; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. Palomba:Hemedicus: Other: Immediate Family Member, Speakers Bureau ; Merck & Co Inc.: Other: Immediate Family Member, Consultancy (includes expert testimony); Seres Therapeutics: Other: Immediate Family Member, Equity Ownership and Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals: Other: Immediate Family Member, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Noble Insights: Consultancy; Evelo: Other: Immediate family member, Equity Ownership; MSK (IP for Juno and Seres): Other: Immediate Family Member, Patents & Royalties - describe: intellectual property rights . Shah:Amgen: Research Funding; Janssen: Research Funding. Perales:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Kyte/Gilead: Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees; Medigene: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Research Funding; NexImmune: Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy; GSK: Consultancy. Straus:Elsevier (PracticeUpdate): Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Hope Funds for Cancer Research: Membership on an entity's Board of Directors or advisory committees. Younes:BMS: Research Funding; Syndax: Research Funding; Genentech: Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Curis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Honoraria; Biopath: Consultancy; Xynomics: Consultancy; Epizyme: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; HCM: Consultancy; Takeda: Honoraria; Pharmacyclics: Research Funding; AstraZeneca: Research Funding. Zelenetz:MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: 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; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: 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; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moskowitz:Merck: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Research Funding; Genentech: Consultancy, Research Funding. OffLabel Disclosure: Brentuximab vedotin is not FDA approved for use in the second-line setting for Hodgkin lymphoma.