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This phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

Introduction: The transformation of chronic lymphocytic leukemia (CLL) into a highly aggressive B-cell lymphoma histology, known as Richter's syndrome (RS), is associated with rapid progression and remains a serious treatment challenge. Standard chemoimmunotherapy approaches often yield poor response rates, short remission durations, and limited overall survival. The role of radiation therapy (RT) in the management of RS has not been explored, and decision making regarding the use of RT in RS is extrapolated from the de novo diffuse large B cell lymphoma (DLBCL) literature. Herein, we report, to the best of our knowledge, the largest case series of patients with RS who received RT. Methods: We conducted a retrospective review of all patients Memorial Sloan Kettering Cancer Center diagnosed with DLBCL RS between April 2002 and August 2020 who received RT at any time following RS diagnosis. Baseline characteristics, information regarding CLL- and RS-directed therapy, RT characteristics including its therapeutic intent, and outcomes were collected. Progression free and overall survival (PFS, OS) were estimated using Kaplan Meier method. All other analyses were descriptive. Analyses were performed using STATA 17.0. Results: 34 RS patients who received RT were identified. Twenty-one received RT as part of a definitive therapeutic strategy while 13 received RT solely for palliation. Baseline characteristics for the entire cohort, as well as divided by RT therapeutic intent, are described in Table 1. Patients received a median of 1 (range 0-5) prior line of CLL-directed therapy prior to RS diagnosis; 24% had prior ibrutinib while 9% had prior venetoclax. Patients received a median of 2 (range 0-5) lines of RS-directed therapy prior to RT; chemoimmunotherapy was first-line RS-directed therapy for 82%. Figure 1 depicts a swimmer's plot for all patients from time of RS diagnosis and includes timing of RT and cellular therapy (CAR-T or allogeneic stem cell transplant, alloSCT). Heterogeneity in the parameters of radiation utilized reflected diverse clinical situations in this cohort. Across the cohort, most commonly irradiated areas included head and neck sites (n=11), abdomen (n=5), paraspinal (n=4) and pelvis/groin (n=4). Median delivered dose was 30.6 Gy (range: 18-54) and 25 Gy (range: 4.5-45) for the definitively and palliatively-treated patients, respectively. Four patients (3 palliative, 1 consolidative) did not complete prescribed course of RT. We subsequently focused on 21 patients treated with RT as part of a definitive therapeutic strategy. With a median follow-up time of 5.8 (range 0.2 - 18.5) years, median OS was estimated to be 6.8 years from RS diagnosis. Fourteen patients (67%) experienced DLBCL progression following RT. A subset of 12 patients received RT following chemoimmunotherapy without immediate cellular therapy in the front-line setting (58%; 7/12) or relapsed/refractory setting (42%; 5/12). Response at the time of RT was CR/clinical CR in 7 patients (58%), PR in 3 (25%), and PD in 1 (8%); response at the time of RT was unknown for 1 patient. In this subset, four (33%) experienced RS disease relapse with 2 occurring within the prior radiation field and 2 occurring distantly. Two patients received RT as an up-front therapy prior to any chemoimmunotherapy in the setting of localized disease. One of these two subsequently had a DLBCL relapse within the prior radiation field. RT was used as a bridging strategy to cellular therapy in 7 patients including alloSCT (n=4) and CAR-T (n=3). Four patients experienced RS relapse. Estimated median PFS was 1.1 years and median OS was 1.9 years from time of cellular therapy. Conclusion: In the largest single-institution series to describe the use of RT in RS, patients who received RT for the diagnosis of RS experienced favorable long-term survival when used as part of a definitive therapeutic strategy, including consolidation following chemoimmunotherapy and as bridging to cellular therapy. These data suggest a role for RT in the management of RS to be further explored through multicenter collaborations and prospective studies. Figure 1 Figure 1. Disclosures Thompson: VJHemOnc: Honoraria; Curio Science: Honoraria; MJH Life Sciences: Honoraria. Mato: Acerta/AstraZeneca: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; Nurix: Research Funding; Sunesis: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Genmab: Research Funding; AstraZeneca: Consultancy; DTRM BioPharma: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Johnson and Johnson: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; MSKCC: Current Employment. Roeker: AbbVie, AstraZeneca, Janssen, LOXO, Pharmacyclics, TG Therapeutics, Vaniam Group, Verastem: Consultancy; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Consultancy; Loxo Oncology: Consultancy; Abbot Laboratories: Current equity holder in publicly-traded company.

Introduction: World Marrow Donor Association (WMDA) promotes global collaboration for the benefit of stem cell donors and transplant patients. WMDA activities include recording the number of unrelated hematopoietic stem cell (HSC) donations globally. Because the COVID-19 pandemic also has an impact on the treatment of patients with other diseases, we hypothesise that it also impacted the practice of unrelated hematopoietic stem cell transplantation (HSCT). We used the 2020 WMDA data to examine the trends in unrelated HSC donations during the COVID-19 pandemic globally, per continent and per country/region. Methods: Donor registries (DRs) and cord blood banks (CBBs) from 61 countries participated in the 2020 survey, compared to 59 countries in the 2019. Slight differences in participation between the data sets of 2019 and 2020 do not explain the trends we observe in HSC donations. Country/region-specific COVID-19 data on cases and deaths were obtained from the data repository operated by the Johns Hopkins University Center for Systems Science and Engineering(https://github.com/CSSEGISandData/COVID-19, accessed July 12, 2021); and population data were retrieved from the Worldometer website(https://www.worldometers.info/, accessed July 12, 2021). Results: HSC donations from unrelated donors (peripheral blood stem cells (PBSC) and bone marrow (BM)) decreased from 20,330 in 2019 to 19,623 in 2020 (-3.5%), compared to an average annual growth rate of 3.9% from 2015 to 2019 (figure 1). The 3.5% decrease is composed of a 29.0% decrease for BM and a 2.6% increase for PBSC, resulting in a drop in the BM share of unrelated HSC donations from 19.3% in 2019 to 14.2% in 2020. The number of cord blood unit (CBU) shipments globally decreased with 3.5% from 2,851 to 2,750. The percentage of national use of HSC products (PBSC and BM) increased from 51.2% to 53.5%. When considering the continent on which the patient is transplanted (table 1), the change rate of use of HSC donated products in 2020 vs. 2019 ranged from -28.0% in South America to +18.2% in Africa. In absolute numbers, the largest decrease of HSC donations occurred for patients in Asia (n=-485) followed by Europe (n=-205), and the largest increase occurred in North America (n=+88) followed by Oceania (n=+25). The share of HSC donations requiring intercontinental transport decreased from 24.6% in 2019 to 21.9% in 2020. In terms of the country/region of transplant (table 2), the largest percentage decrease occurred in Colombia (-90,5%) followed by Russia (-55,5%). In absolute numbers, the largest decrease occurred in Turkey (-147), with Japan following (-128, although Japan saw an increase of CBU use of +106). The highest growth rate was observed in Iran (+28,7%), followed by South Africa (+28,2%). In absolute figures, the greatest increase occurred in Italy (+67). The two countries receiving the largest HSC donation numbers showed no major changes versus the previous year: USA: +0.6% (although a decrease for CBU of -21,0% was observed) and Germany: -2.4%. We did not find any significant correlation between the numbers of COVID-19 cases or COVID-19-related deaths per 1 million inhabitants with the HSC donation numbers (Spearman's r=0.05 for cases and =0.08 for deaths). Discussion: The decline in the number of unrelated HSC donations in 2020 suggests an impact of the COVID-19 pandemic on HSC donation and unrelated HSCT. The significant decrease in BM collections and intercontinental/cross-border shipments can be explained by logistically complex processes, as well the increased risk to the donor of being exposed to an operative procedure. CBU as a stem cell source potentially circumvents these logistical complications. However, on a global scale our data does not show increased use of CBU suggesting that decisions to use CBU as a stem cell source did not change in the pandemic . We were unable to demonstrate a correlation between country/region-specific severity of the pandemic and HSC donation numbers. We suspect this is due to the data quality of reported number of COVID-19 cases and COVID-19-related deaths. Also, we did not gather monthly data and therefore could not specify pandemic waves. In conclusion, we would like to point out the fact that global exchanges of HSC products continued and only decreased slightly is an extraordinary achievement of DRs, CBBs and their donors and is a testament to the importance of international collaborations in the WMDA. Figure 1 Figure 1. Disclosures Devine: Orca Bio: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding; Be the Match: Current Employment. Shaw: Orca bio: Consultancy; mallinkrodt: Other: payments. Forman: Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company; Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy.

Background: Targeted therapies including ibrutinib, acalabrutinib and venetoclax (ven) have fundamentally changed the treatment of patients (pts) with chronic lymphocytic leukemia (CLL) leading to improved outcomes and durable remissions for many pts. However, CLL remains an incurable disease and a subset of pts will ultimately have progressive CLL following treatment with a covalent Bruton's Tyrosine Kinase inhibitor (cBTKi, e.g., ibrutinib, acalabrutinib) and ven. Data on efficacy of therapies for "double exposed" pts (i.e., pts exposed to both a cBTKi and ven) are extremely limited. Available approved options include chemoimmunotherapy (CIT) and phosphatidylinositol 3-kinase inhibitors (PI3Ki). However, the landmark clinical trials leading to the approvals of CIT and PI3Kis did not include pts treated with either cBTKi or ven (Furman et al. NEJM 2014, Flinn et al. Blood 2018). Non-covalent BTKis (ncBTKi) and chimeric antigen receptor (CAR) T-cell therapy have demonstrated promising clinical activity in double exposed CLL pts in clinical trials (Mato et al. Lancet 2021, Siddiqi et al. ASH 2020), but have not yet been compared to other novel agents or CIT in clinical trials or real-world analyses. We sought to describe outcomes of therapies for "double exposed" CLL pts. Methods: A retrospective, international, multicenter study was conducted. CLL pts were included if they received a cBTKi and ven and then a subsequent CLL-directed therapy. Therapies for Richter Transformation were excluded. Investigators identified pts at each site and collected data on demographics, disease characteristics, prior therapies, subsequent therapies and response assessments. Information was collected on up to three subsequent lines of therapy (LOT 1-3) per patient. The primary study endpoint was investigator-assessed overall response rate (ORR) per iwCLL 2018 criteria to therapies (LOT 1-3) following both cBTKi and ven. Kaplan-Meier method was used to estimate progression free survival (PFS). All other analyses were descriptive. Analyses were performed using STATA 17.0. Results: We report outcomes on 125 CLL pts who had prior cBTKi and ven and received a subsequent LOT. Baseline characteristics are presented in Table 1. ORR to prior cBTKi was 84.7% and 69.6% to prior ven. The most common reason for discontinuation of prior cBTKi and ven was CLL progression (71.1% cBTKi, 68.8% ven) followed by toxicity (25.6% cBTKi, 16.8% ven). Most common treatment strategies included ncBTKi (n=45), cBTKi (n=43), CIT (n=23), PI3Ki (n=24), alloSCT (n=17), CAR T-cell therapy (n=9), ven re-treatment (n=6), and other (n=44). ORR for selected agents following cBTKi and ven are presented in Table 2. ORR and PFS estimates were as follows: CAR T-cell therapy (85.7%, median PFS 4 months), alloSCT (76.5%, median PFS 11 months), ncBTKi (75.0%, median PFS not reached), PI3Ki (40.9%, median PFS 5 months), CIT (31.8%, median PFS 3 months) and ven re-treatment (ORR 40%, median PFS 14 months). ORR to cBTKi was 53.7%; however, median PFS for pts who discontinued a previous cBTKi for PD was 1 month versus 7 months for pts who discontinued due to AE. Figure 1 shows Kaplan-Meier estimated PFS for ncBTKi, PI3Ki, alloSCT, and CIT. Conclusions: In the largest series of "double exposed" CLL pts, several key findings warrant further investigation and discussion. Practice patterns are variable and no standard of care exists for CLL pts previously treated with a cBTKi and ven. Additionally, approved standard therapies including CIT combinations and PI3Kis yield poor outcomes with responses which are not durable. The low response rates and short PFS for PI3Ki and CIT call into question the use of these therapies as standard comparator arms in planned randomized trials. At this time, ncBTKi has a high ORR with durable responses (median PFS not reached). There appears to be a promising role for alloSCT in select, fit patients (ORR 76.5%, median PFS 11 months), and CAR T-cell therapy should be further explored in this population (ORR 85.7%, median PFS 4 months). Overall, this study highlights a continued unmet need for therapies for "double exposed" CLL pts. Figure 1 Figure 1. Disclosures Thompson: MJH Life Sciences: Honoraria; VJHemOnc: Honoraria; Curio Science: Honoraria. Roeker: Abbot Laboratories: Current equity holder in publicly-traded company; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; TG Therapeutics: Consultancy; AbbVie, AstraZeneca, Janssen, LOXO, Pharmacyclics, TG Therapeutics, Vaniam Group, Verastem: Consultancy; Pfizer: Consultancy, Research Funding. Coombs: LOXO: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria; Genentech: Honoraria; MEI Pharma: Honoraria. Kamdar: AbbVie: Consultancy; TG Therapeutics: Research Funding; SeaGen: Speakers Bureau; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy; Celgene: Other; Celgene (BMS): Consultancy; Kite: Consultancy; KaryoPharm: Consultancy; Genentech: Research Funding; Genetech: Other. Pagel: Epizyme: Consultancy; Incyte/MorphoSys: Consultancy; BeiGene: Consultancy; Pharmacyclics/AbbVie: Consultancy; Actinium Pharmaceuticals: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy; Kite, a Gilead Company: Consultancy; MEI Pharma: Consultancy. Jacobs: MEI Pharma: Research Funding; Adaptive Biotechnologies: Consultancy; Genentech: Consultancy; TG Therapeutics: Research Funding, Speakers Bureau; Verastem: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy; TeneoBio: Research Funding; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Jannsen: Speakers Bureau; SecuraBio: Consultancy, Speakers Bureau. Hill: Gentenech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Celgene (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Brander: AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding; ArQule: Research Funding; DTRM: Research Funding; LOXO: Research Funding; Verastem: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding; Novartis: Research Funding; Ascentage: Research Funding; MEI Pharma: Research Funding; Genentech: Consultancy, Research Funding; NCCN: Other: panel member; Pfizer: Consultancy, Other: Biosimilars outcomes research panel; ArQule/Merck: Consultancy. Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy. Ujjani: AbbVie: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Research Funding; Adaptive Biotechnologies: Research Funding; Atara Bio: Consultancy; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; TG Therapeutics: Honoraria; Gilead: Honoraria; ACDT: Honoraria; Kite, a Gilead Company: Honoraria. Battiato: Abbvie: Honoraria; Janssen: Honoraria. Rhodes: AbbVie, Genentech, Pharmacyclics, TG Therapeutics: Other: Consultant; Conquer Cancer Foundation Young Investigator Award: Other: Grant/Research Support. Fakhri: Loxo/Lilly: Research Funding. Barr: Morphosys: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy; TG Therapeutics: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Beigene: Consultancy; Bristol Meyers Squibb: Consultancy; Abbvie/Pharmacyclics: Consultancy; Genentech: Consultancy. Portell: TG Therapeutics: Honoraria, Research Funding; SeaGen: Research Funding; Kite: Honoraria, Research Funding; Xencor: Research Funding; Abbvie: Research Funding; Pharmacyclics: Honoraria; Merck: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Acerta/AstraZeneca: Research Funding; Aptitude Health: Honoraria; Targeted Oncology: Honoraria; Morphosys: Honoraria; Genentech: Research Funding; VelosBio: Research Funding. Lamanna: AbbVie: Consultancy, Research Funding; Verastem Oncology: Research Funding; BeiGene: Consultancy; Pharmacyclics: Consultancy; Celgene Corporation: Consultancy; Oncternal Therapeutics: Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy; Gilead Sciences, Inc.: Consultancy; MingSight Pharmaceuticals, Inc.: Research Funding; Genentech, Inc.: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; TG Therapeutics, Inc: Research Funding; Juno Therapeutics, Inc.: Research Funding. Zelenetz: MorphoSys: Honoraria; Verastem: Honoraria; LFR: Other; Gilead: Honoraria, Research Funding; NCCN: Other; AstraZeneca: Honoraria; MEI Pharma: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria; BMS/Celgene/JUNO: Honoraria, Other; Novartis: Honoraria; SecuraBio: Honoraria; Genentech/Roche: Honoraria, Research Funding; MethylGene: Research Funding; Amgen: Honoraria; Beigene: Honoraria, Other, Research Funding. Schuster: Abbvie: Consultancy, Research Funding; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; Adaptive Biotechnologies: Research Funding; BeiGene: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; DTRM: Research Funding; Genetech: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Incyte: Research Funding; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Merck: Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Pharmaclcyclics: Research Funding; Tessa Theraputics: Consultancy; TG Theraputics: Research Funding. Eyre: Secura Bio: Consultancy, Honoraria; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Research Funding; Incyte: Consultancy; Beigene: Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Janssen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences. Mato: MSKCC: Current Employment; AstraZeneca: Consultancy; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Johnson and Johnson: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Nurix: Research Funding.

Background: TP53 mutations occur in 10-20% of patients with AML, constitute high-risk disease as per ELN criteria, and confer poorer prognosis. Venetoclax combination therapies and CPX-351 were recently approved for AML treatment and lead to improved outcomes in subsets of high-risk AML, however the most effective approach for treatment of TP53-mutated (m) AML remains unclear. In this study we explored the clinical outcome of TP53m AML patients treated over the last 8 years as novel therapies have been introduced to our therapeutic armamentarium. Methods: We conducted a multicenter observational study in collaboration with 4 U.S. academic centers and analyzed clinical characteristics and outcome of 174 TP53m AML patients diagnosed between March 2013 and February 2021. Mutation analysis was performed on bone marrow specimens using 42, 49, 199, or 400 gene targeted next generation sequencing (NGS) panels. Patients with an initial diagnosis of AML were divided into 4 groups (GP) based on the progressive use of novel therapies in clinical trials and their approvals as AML induction therapy during different time periods: 2013-2017 (GP1, n= 37), 2018-2019 (GP2, n= 53), 2019-2020 (GP3, n= 48) and 2020-2021 (GP4, n= 36) to analyze difference in outcome. Results: Baseline characteristics were not significantly different across different GP, as shown in Table 1. Median age of patients was 68 (range [R], 18-83), 65 (R, 29-88), 69 (R, 37-90) and 70 (R, 51-97) years in GP1-4, respectively (p=0.40). The percentage of patients with de novo AML/secondary AML/therapy-related AML in GP1-4 was 40/40/20, 36/29/24, 37.5/37.5/25 and 28/52/20, respectively (p=0.82). The proportion of patients with complex cytogenetics (CG) was 92%, 89%, 96% and 94% in GP1-4, respectively (p=0.54). The median TP53m variant allele frequency (VAF) was 48% (range [R], 5-94), 42% (R, 5-91), 45% (R, 10-94) and 60% (R, 8-82) in GP1-4, respectively (p=0.38). Four (11%), 13 (24.5%), 10 (21%) and 9 (25%) patients had multiple TP53 mutations in GP1-4, respectively (p=0.33). The proportion of patients who received 3+7 (30%, 16%, 6% & 8%; p=0.01), HMA only (11%, 18%, 2% & 8%; p=0.06), venetoclax-based (2.5%, 12%, 48%, & 61%; p The median progression-free survival was 7.7, 7.0, 5.1 and 6.6 months in GP1-4, respectively (p=0.60, Fig 1A). The median overall survival (OS) was 9.4, 6.1, 4.0 and 8.0 months in GP1-4, respectively (p=0.29, Fig 1B). In univariate analysis for OS, achievement of CR/CRi (p Conclusion: We present the largest experience with TP53m AML patients analyzed by NGS. Although outcomes were almost universally dismal, alloHCT appears to improve the long-term survival in a subset of these patients. Effective therapies are warranted to successfully bridge patients to alloHCT and to prolong survival for transplant ineligible patients. Figure 1 Figure 1. Disclosures Badar: Pfizer Hematology-Oncology: Membership on an entity's Board of Directors or advisory committees. Litzow: Omeros: Other: Advisory Board; Pluristem: Research Funding; Actinium: Research Funding; Amgen: Research Funding; Jazz: Other: Advisory Board; AbbVie: Research Funding; Astellas: Research Funding; Biosight: Other: Data monitoring committee. Shallis: Curis: Divested equity in a private or publicly-traded company in the past 24 months. Goldberg: Celularity: Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Aprea: Research Funding; Arog: Research Funding; DAVA Oncology: Honoraria; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Prelude Therapeutics: Research Funding; Aptose: Consultancy, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Atallah: BMS: Honoraria, Speakers Bureau; Takeda: Consultancy, Research Funding; Amgen: Consultancy; Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Research Funding. Foran: revolution medicine: Honoraria; gamida: Honoraria; bms: Honoraria; pfizer: Honoraria; novartis: Honoraria; takeda: Research Funding; kura: Research Funding; h3bioscience: Research Funding; OncLive: Honoraria; servier: Honoraria; aptose: Research Funding; actinium: Research Funding; abbvie: Research Funding; trillium: Research Funding; sanofi aventis: Honoraria; certara: Honoraria; syros: Honoraria; taiho: Honoraria; boehringer ingelheim: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding.

The upper age-limit for patients with hematological malignancies eligible for allo-SCT progressed to 70-75 years. As a consequence, an increase of older patients submitted to allo-SCT has been observed worldwide and in Italy as well. This registry-based retrospective study on behalf of GITMO (GITMO AlloEld) describes the transplant activity among elderly patients in Italy, between 2000 and 2017. Thiry GITMO Centers participated to the Study. 2061 allo-SCTS in patients older than 60 years were exported from PROMISE database and 1996 first transplants were analysed. The median age of the patients at transplant was 63,5 years (59,5-77,8). The most commonly transplanted diseases were acute leukemias and myelodisplastic syndromes (67,5%). 28% and 27% of the patients showed a HCT-CI of 1-2 or grater than 3, respectively. The KPS was 100% in 27,2% and 90% in 42,9% of the cases. 32% of the patients received a myeloablative conditioning regimen and 55% of the patients received an in vivo T-cell depletion (either post transplant cyclophosphamide or ATG). With a median follow up of 10,4 years, the OS at 5 years significantly improved during time, moving from 28% between 2000-2005 to 37% between 2012-2017 (p=0,012). This was related to a significant reduction in RI (45% vs 30%, p The following significant differences were observed across the years of the present study: 1) a longer 5 years OS in patients younger than 65 years (34%) vs those older than 70 years (19%) between 2000 and 2011 only (p=0,003) (Figure 1A and 1B); 2) a longer 5 years OS (p3 between 2000-2011 only (Figure 2A and 2B); 3) a different 5 years OS according to donor type between 2000 and 2011 only (19% for haplo vs 31% for sibling vs 33% for mismatch UD and 38% for MUD; p 4) a reduction in the incidence of extensive cGVHD at 1 year (15,6% between 2000 and 2005 vs 10,3% between 2012 and 2017, p=0,004) (Figure 4). Comparing 2000-2005 vs 2012-2017, the major significant differences of the patients regard: the baseline disease (more AL/MDS: 40% vs 77%; p 3 moved from 10% to 30% (p By multivariate analysis MUD donor or UCB, no response at the time of SCT and male recipient significantly impaired OS, whereas HCT-CI These retrospective data showed that the transplant procedure for elderly patients became safer and more effective over time, for a reduction of the RI related to a better selection of patients (more acute leukemias in CR) and a better selection of conditionings (more MAC and more alkylators). Nowdays, the HCT-CI score is probably not sufficient for estimate elderly patients probability of OS and NRM. Figure 1 Figure 1. Disclosures Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment.

Introduction. Bcl-2 family proteins comprise anti-apoptotic and pro-apoptotic proteins. Interaction between these proteins, as well as severe regulation of their expression, mediates cell survival and can quickly induce cell death. Venetoclax is Bcl-2-targeting that has shown preclinical and clinical activity in hematologic malignancies. Due to the development of resistance and the loss of dependence on the target protein, the monotherapy may be insufficient for maximal effectiveness. To circumvent the resistance mechanisms, many preclinical studies have shown that combination of venetoclax with other agents may represent a more effective therapeutic strategy. Ubiquitin-proteasome signaling pathway is a potential target that plays an important role in the proteolysis of key regulatory proteins. Proteasome inhibitors include ixazomib that inhibits cell growth and induces apoptosis in hematological malignancies cells resistant to conventional therapies and bortezomib. Objective: To analyze the preclinical efficacy and associated biological effects of venetoclax combined with ixazomib in a panel of lymphoma cell lines with diverse expression levels of Bcl-2 and other Bcl-2 family proteins. Methods: 12 lymphoma cell lines including FL (RL, WSU-NHL, Karpas422), MCL (Jeko1, Granta519), DLBCL (OCI-LY3, OCI-LY18), CTCL (Hut-78), ALCL (Karpas299), HL (L1236, L540), CLL (Mec1) and two MCL primary patient samples were exposed to venetoclax (0.01 - 8 µM) and ixazomib (10 - 2000 nM) alone for 24 - 72 hours to calculate IC50. Subsequently, lymphoma cells were exposed to venetoclax (0.015 - 25 nM) in combination with ixazomib (0.015 - 0.5 nM) for 24 hours. Cell viability was determined by MTT. Coefficient of synergy (combination index - CI) was calculated using CalcuSyn. Cell cycle and induction of apoptosis were evaluated by flow cytometry and changes in Bcl-2 family members, caspase activation and AKT phosphorylation were determined by western blotting. Results. In vitro, venetoclax and ixazomib alone induced cell death in a dose- and time-dependent manner against lymphoma cell lines. The IC50 is between 0.5 and 8 µM for venetoclax and between 12 and 1250 nM for ixazomib. The combination of venetoclax (0.03, 0.06, 12.5, 25 nM) with ixazomib (0.03, 0.06, 0.25, 0.5 nM) produced a synergistic effect (CI < 1) after 24 h of treatment in the most lymphoma cells lines leading to inhibition of cell growth and induction of apoptosis between 26 % and 59 % accompanied by increased with cleavage of caspases-3, -9 and PARP. We observed an additive effect (CI = 1) in Jeko1 (MCL) and MEC1 cells (CLL) and antagonist effect (CI > 1) Hut-78 cells (CTCL). Synergistic effect has been seen in two MCL primary patient samples (CI = 0.5 - 0.7). In sensitive lymphoma cells, the combination abrogated colony formation in the methylcellulose medium. When lymphoma cell lines were co-cultured with mesenchymal stromal cells with both drugs we observed a decrease of cell viability and a fraction of apoptotic cells indicating that drug combination may overcome the tumor promoting effects of stromal cells. The apoptosis induced in FL and Granta519 cells (MCL) by drug combination was accompanied by partial downregulation of Bcl-2 and strong upregulation of Bax, Bad, Bim and Noxa proteins. Jeko-1 cells were less sensitive to venetoclax-ixazomib combination-induced apoptosis. Western blot analysis showed a differential expression of Bcl-2, Mcl-1 and Bcl-XL proteins in FL, MCL and HL cell lines. Jeko-1 cells showed a normal expression of Bcl-2 and Mcl-1 proteins and high Bcl-xL protein level. Co-expression of related anti-apoptotic Bcl-2 family proteins could limit activity of treatment. Combined treatment induced G0/G1 cell cycle arrest and increased the sub-G1 population that was linked by the upregulation of p27 and p21. In addition, in RL, WSU-NHL and Granta519, enhanced cell death is associated with AKT inactivation and with a reduction of p-4EBP1, leading to decreased levels of c-MYC. Conclusion. Venetoclax exhibits strong synergistic activity with ixazomib in lymphoma cells. Studies are still ongoing and signaling pathways that promote the combination of venetoclax with ixazomib are to be analyzed. These data offer a rationale to continue exploring venetoclax-ixazomib combination and suggest that suppression of Bcl-2 family protein driven survival signaling may be one important mechanism for combination synergy. Disclosures No relevant conflicts of interest to declare.

Introduction: Mediastinal gray zone lymphoma (MGZL) is an extremely rare form of non-Hodgkin lymphoma with a predominance in young men and with features that are intermediate between nodular sclerosis classical Hodgkin lymphoma (cHL) and primary mediastinal B-cell lymphoma (PMBL). Shared features of these tumor types include tumor CD30 expression and the presence of 9p24.1 chromosomal alterations with expression of programmed death 1 (PD-1) ligand. Compared with PMBL, patients (pts) with MGZL have inferior survival outcomes when treated with conventional chemotherapy (Wilson et al. Blood 2014). Nivolumab is a fully human immunoglobulin G4 anti-PD-1 immune checkpoint inhibitor monoclonal antibody; brentuximab vedotin (BV) is an anti-CD30 antibody-drug conjugate. In the CheckMate 436 study, the combination of nivolumab and BV demonstrated a high objective response rate (ORR; 73%) and complete response (CR) rate (37%) in pts with relapsed/refractory (R/R) PMBL (Zinzani et al. J Clin Oncol 2019). A separate study in R/R cHL also showed impressive efficacy (ORR: 82%; CR: 61%), suggesting some complementary action between the two agents (Herrara et al. Blood 2018). A case series highlighted the clinical activity of PD-1 inhibitor monotherapy in R/R MGZL (Melani et al. N Engl J Med 2017). Given the overlapping features of MGZL with PMBL and cHL, we evaluated the efficacy and safety of nivolumab + BV in a separate MGZL cohort in CheckMate 436. Methods: The expansion cohort of the open-label, phase 1/2 CheckMate 436 (NCT02581631) study enrolled pts ≥ 18 years old with ECOG performance status of 0 or 1, and with confirmed R/R MGZL after autologous hematopoietic cell transplantation (auto-HCT) or, if ineligible for auto-HCT, after ≥ 2 multi-agent chemotherapy regimens. Pts received 240 mg nivolumab (on Day 8 of Cycle 1, then Day 1 of following cycles) and 1.8 mg/kg BV (on Day 1 of each cycle) every 3 weeks until disease progression or unacceptable toxicity. Primary endpoints were investigator-assessed ORR per the Lugano 2014 criteria and safety. Key secondary endpoints included CR rate, overall survival (OS), duration of response (DOR), and progression-free survival (PFS). Results: A total of 10 pts were treated and evaluable. Median age (range) was 35 (25-72) years, with only 1 pt aged > 65 years (72 years). Six pts (60%) were male; all pts had a mediastinal mass. Pts had a median of 2 prior lines of systemic cancer therapy, and none had received prior auto-HCT. At database lock, 8 months after the last pt received the first treatment, all pts had discontinued treatment (5 due to disease progression, 3 due to maximum clinical benefit, 1 due to allogenic [allo]-HCT, and 1 due to auto-HCT). Pts received a median of 7 doses of nivolumab and 7 doses of BV. ORR per investigator was 70% (80% CI, 45-88), with 5 pts (50%) achieving CR (Table). The time to CR was 1.2-1.3 months and the duration of CR was 1.5-3.2 months before pts were censored for subsequent therapy. The 5 pts who achieved CR were bridged to hematopoietic cell transplantation (4 allo- and 1 auto-HCT) and censored (all were alive at database lock). Eight pts (89%) who were evaluable for response had tumor reduction of > 25% (Figure). At a median follow-up of 12.4 (range, 0.1-25.5) months, the 6-month OS rate was 80.0% (95% CI, 40.9-94.6). DOR and PFS could not be estimated due to earlier censoring of pts who received subsequent therapies. Nine pts (90%) experienced any grade treatment-related adverse events (TRAEs); the most common any grade TRAEs were neutropenia (n = 3; 1 grade 1, 1 grade 2, 1 experienced 4 grade 1/2 events and 1 grade 3 event) and paresthesia (n = 3; all grade 1). Three pts (30%) had grade 3-4 TRAEs. Infusion-related reaction occurred in 1 pt (grade 1). One pt had an immune-mediated AE (grade 2 maculo-papular rash, which resolved without systemic steroids). A serious drug-related AE occurred in 1 elderly pt (grade 3 febrile neutropenia). There were 3 deaths, all caused by disease progression. Conclusions: Nivolumab + BV demonstrated a high investigator-assessed ORR of 70%, with a 50% CR rate and a tolerable safety profile in pts with R/R MGZL, similar to findings in PMBL. The regimen represents a potential option for bridging to hematopoietic cell transplantation based on the brisk and frequent responses and a safety profile that compares favorably with historic data using standard chemotherapy regimens. Study support: BMS. Writing support: Jane Cheung, Caudex, funded by BMS. Figure 1 Disclosures Santoro: Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Arqule, Sanofi: Consultancy; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau. Moskowitz:Merck: Consultancy; Imbrium Therapeutics, L.P.: Consultancy; Miragen Therapeutics: Consultancy; Incyte: Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Consultancy. Carlo-Stella:Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; Boehringer Ingelheim and Sanofi: Consultancy; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding. Fanale:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Francis:Bristol-Myers Squibb Company: Current Employment, Current equity holder in publicly-traded company. Sacchi:Bristol-Myers Squibb Company: Current Employment. Savage:Roche (institutional): Research Funding; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie, Servier: Consultancy; BeiGene: Other: Steering Committee; Merck, BMS, Seattle Genetics, Gilead, AstraZeneca, AbbVie: Honoraria. OffLabel Disclosure: Nivolumab was used in combination with brentuximab vedotin (BV) for evaluation of its efficacy and safety in patients with relapsed/refractory mediastinal gray zone lymphoma.

Introduction Brentuximab vedotin (BV) targets CD30, a receptor expressed on the Reed-Sternberg cells of classic Hodgkin lymphoma (cHL). Nivolumab (Nivo) restores antitumor immunity by blocking the PD-1 receptor on activated T-cells. In this phase 1/2 study, combination treatment (tx) with BV + Nivo demonstrated durable efficacy in patients (pts) with relapsed/refractory (R/R) cHL (Herrera, Blood 2018; NCT02572167). Biomarkers consistent with innate and adaptive immune activation were observed in the peripheral blood of pts treated with the combination regimen. Herein, we associate biomarkers in the peripheral blood with clinical response, and present follow-up results for pts who received BV + Nivo under staggered and concurrent dosing schedules. Methods Enrolled pts had cHL that relapsed or was refractory to frontline chemotherapy. In Parts 1 and 2 (staggered dosing), pts received up to 4 cycles of BV 1.8 mg/kg and Nivo 3.0 mg/kg given on Days 1 and 8 of Cycle 1, respectively, and together on Day 1 of Cycles 2-4. Pts in Part 3 (concurrent dosing) received the same dose of both agents on Day 1 of all 4 cycles. After investigators assessed response (Cheson 2014, with the incorporation of LYRIC [Cheson 2016] for pts in Part 3), pts could undergo ASCT. Results Demographics and baseline characteristics were similar across all treated pts (N=91) in the staggered and concurrent dosing cohorts; median age 34 years (yrs, range; 18-69), 42% with primary refractory disease, and 30% with relapse within 1 yr of frontline therapy. All 91 pts are off-tx and have been observed through the 100-day safety reporting period. A total of 86 pts (92%) completed all 4 cycles of BV + Nivo. Early tx discontinuations were due to; AE (peripheral neuropathy and increased GGT [1 pt each]), progressive disease (PD), investigator decision, and pt decision (1 pt each). Most common AEs prior to ASCT or additional salvage therapy were nausea (52%) and infusion-related reactions (IRRs, 43%). Excluding IRRs, 14% of pts had immune-related AEs requiring tx with systemic steroids, including rash (8%), pneumonitis (4%), and AST increased, diarrhea, and Guillain-Barre syndrome (1% each). The ORR for all-treated pts was 85%, with 67% complete response (CR). A total of 67 pts (74%) underwent ASCT after tx with BV + Nivo. There were 22 pts who received additional salvage therapy after BV + Nivo (7 PD, 6 partial response, 5 stable disease, and 4 CR at EOT), 17 of whom later underwent ASCT. At a median of 22.6 months (range; 1.2, 41.2) from the start of tx, the estimated 2-yr PFS rate in all treated pts was 78%, and for pts who underwent ASCT after tx with BV + Nivo was 91% (Figure 1). At 2 years, the estimated OS rate for all treated pts was 93%. Staggered and concurrent dosing of BV + Nivo resulted in increased levels of activated and dividing CD4+ T cells, activated and dividing CD8+ T cells (concurrent dosing-only), regulatory T cells (Tregs), and circulating plasmablasts in blood. We did not observe any associations between the magnitude of these changes and clinical response. Pts with CR exhibited trends for higher pre-tx blood levels of CD30+ Tregs and CD30+ Th subsets compared to pts without CR, suggesting BV depletion of these populations may have a role in the clinical mode of action of BV + Nivo. Although pre-tx levels of cytotoxic lymphocytes (CTLs) in blood did not differentiate pts with CR from other pts, pts in the lower quartile of pre-tx CTL levels showed significantly shorter PFS than other pts, suggesting a potential association between CTLs and disease control. Changes in blood cytokine and chemokine levels were observed after BV + Nivo, including increased levels of IL-18, IP-10, I-TAC, and sCD30, and decreased levels of TARC, IL-2Ra, and IL-6. Our analyses support strong correlations between pre-tx cytokine/chemokine levels and clinical benefit including trends linking lower pre-tx levels of IL-18, I-TAC, and IL-2RA to achieving CR and longer PFS. Conclusion BV + Nivo, both staggered and current dosing, showed tolerability and high CR rates with durable remissions among pts with R/R cHL. Analysis of blood biomarkers identified trends potentially linking baseline levels of CD30+ immune cells and the baseline pt inflammatory state with the activity of BV + Nivo. Together, these encouraging results support further investigation of BV + Nivo as initial salvage therapy in pts with R/R cHL. Figure 1 Disclosures Moskowitz: Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Merck: Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Merck: Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Incyte: Research Funding; Merck: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding. Advani:Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Forty-Seven: Research Funding; Infinity Pharma: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Merck: Research Funding; Kura: Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agensys: Research Funding; Cell Medica, Ltd: Consultancy; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Millennium: Research Funding; Janssen: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bartlett:Affimed Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Dynavax: Research Funding; Forty-Seven: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medimmune: Research Funding; Merck: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vose:Acerta Pharma: Honoraria, Other: Grants, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Celgene Corporation: Research Funding; Incyte Corporation: Research Funding; Kite Pharma: Honoraria, Other: Grants, Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; AbbVie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Legend Pharmaceuticals: Honoraria. Ramchandren:Genentech: Research Funding; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Pharmacyclics LLC, an Abbvie company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Sandoz-Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Feldman:Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Trillium: Research Funding; Viracta: Research Funding. LaCasce:BMS: Consultancy; Research to Practice: Speakers Bureau; Humanigen: Consultancy; Seattle Genetics: Consultancy, Research Funding. Christian:Bristol-Myers Squibb: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cephalon: Research Funding; Janssen: Research Funding; Immunomedics: Research Funding; Celgene: Research Funding; Acerta: Research Funding; Triphase: Research Funding; Millennium Pharmaceuticals Inc: Research Funding; Merck: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding. Moskowitz:ADC Therapeutics: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Celgene: Consultancy; Pharmacyclics: Research Funding. Brown:Seattle Genetics, Inc.: Employment, Equity Ownership. Taft:Seattle Genetics, Inc.: Employment, Equity Ownership. Ansari:Seattle Genetics, Inc.: Employment, Equity Ownership. Zak:Seattle Genetics, Inc.: Employment, Equity Ownership. Sacchi:Seattle Genetics, Inc.: Research Funding. Manley:Seattle Genetics: Employment, Equity Ownership. Herrera:Merck: Consultancy, Research Funding; AstraZeneca: Research Funding; Adaptive Biotechnologies: Consultancy; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding.