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The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy.

Aging is associated with impaired hematopoietic and immune function caused in part by decreased fitness in the hematopoietic stem cell (HSC) population and an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. Here we demonstrate that older specific pathogen free (SPF) wild-type (WT) mice in contrast to young SPF mice produce more interleukin-1a and interleukin-1b (IL-1a/b) in steady-state bone marrow (BM), with most of the IL-1a/b being derived from myeloid BM cells. Furthermore, blood from steady-state older SPF WT mice contains higher levels of microbe-associated molecular patterns, specifically TLR4 and TLR8 ligands. In addition, BM myeloid cells from older mice produce more IL-1b in vitro, and older mice show higher and more durable IL-1a/b responses upon stimulation with lipopolysaccharide in vivo. To test whether HSC aging is driven by IL-1a/b, we evaluated HSCs from IL-1 receptor 1 (IL-1R1) knockout (KO) mice. Indeed, older HSCs from IL-1R1KO mice show significantly mitigated aging-associated inflammatory signatures. Moreover, HSCs from older IL-1R1KO and from germ-free mice maintain unbiased lymphomyeloid hematopoietic differentiation upon transplantation, thus resembling this functionality of young HSCs. Importantly, in vivo antibiotic suppression of microbiota or pharmacologic blockade of IL-1 signaling in older WT mice was similarly sufficient to reverse myeloid-biased output of their HSC populations. Collectively, our data define the microbiome/IL-1/IL-1R1 axis as a key, self-sustaining and also therapeutically partially reversible driver of HSC inflammaging.

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we aimed to assess survival and safety in ZUMA-1 after 5 years of follow-up. Eligible adults with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) received lymphodepleting chemotherapy followed by axi-cel infusion targeted at 2×106 cells/kg. Investigator-assessed response, updated survival, safety, and pharmacokinetic outcomes were assessed in treated patients. The objective response rate in the 101 treated patients was 83% (58% complete response rate), and with a median follow-up of 63.1 months, responses were ongoing at data cutoff in 31%. Median overall survival (OS) was 25.8 months and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91%. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. ClinicalTrials.gov, number NCT02348216

Background: KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is currently being evaluated in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who received 1 - 5 prior therapies (including a Bruton tyrosine kinase inhibitor) in the Phase 2, registrational, multicenter ZUMA-2 study. With a median follow-up of 12.3 months, we previously reported an objective response rate (ORR) of 93% (67% complete response [CR] rate) with KTE-X19 treatment in the 60 efficacy-evaluable patients in ZUMA-2 (Wang et al. N Engl J Med. 2020;382:1331). Here, we present an updated analysis of efficacy, safety, and pharmacology for all patients with a minimum follow-up of 1 year. Methods: Eligible patients with R/R MCL underwent leukapheresis and conditioning chemotherapy followed by a single infusion of KTE-X19 (2 × 106 CAR T cells/kg; Wang et al. N Engl J Med. 2020;382:1331). The primary endpoint was ORR (CR + partial response) as assessed by an Independent Review Committee according to the Lugano Classification (Cheson et al. J Clin Oncol. 2014;32:3059). Efficacy data are reported for the 60 treated patients with ≥ 1 year of follow-up; safety data are presented for all 68 treated patients. Results: As of December 31, 2019, the median follow-up was 17.5 months (range, 12.3 - 37.6). The ORR was 92% (95% CI, 81.6 - 97.2), with a CR rate of 67% (95% CI, 53.3 - 78.3). Of all efficacy-evaluable patients, 48% had ongoing responses at the data cutoff. Medians were not reached for duration of response, progression-free survival (PFS), or overall survival; 15-month estimates were 58.6% (95% CI, 42.5 - 71.7), 59.2% (95% CI, 44.6 - 71.2), or 76.0% (95% CI, 62.8 - 85.1), respectively. In patients who achieved a CR, the median PFS was not reached (15-month rate, 75.1% [95% CI, 56.8 - 86.5]); in those who achieved a partial response, the median PFS was 3.1 months (95% CI, 2.3 - 5.2). Median PFS was 1.1 months (95% CI, 0.9 - 3.0) in nonresponding patients. The first 28 patients treated had a median follow-up of 32.3 months (range, 30.6 - 37.6); 39.3% of these patients remain in remission with no further therapy. Common grade ≥ 3 adverse events were neutropenia (85%), thrombocytopenia (53%), anemia (53%), and infections (34%). Grade ≥ 3 cytopenias were reported in 60% of patients ≥ 30 days post-infusion. Grade ≥ 3 cytokine release syndrome (CRS; per Lee et al. [Blood. 2014;124:188]) occurred in 15% of patients; 59% received tocilizumab for management of CRS. Grade ≥ 3 neurologic events (NEs) were reported in 31% of patients, and 38% received steroids for NE management. All CRS events and most NEs (37/43) resolved, as previously reported. There were no Grade 5 CRS events or NEs, and no new Grade 5 events occurred with additional follow-up. As previously reported, there were 2 cases of Grade 2 cytomegalovirus infection, 1 case each of Grade ≥ 3 hypogammaglobulinemia and Grade ≥ 3 tumor lysis syndrome, and no cases of Epstein-Barr virus-associated lymphoproliferation, replication-competent retrovirus, hemophagocytic lymphohistiocytosis, or KTE-X19-related secondary cancers. Median peak CAR T cell levels and median area under the curve (Days 0 - 28) were 98.9 cells/µL (range, 0.2 - 2565.8) and 1394.9 cells/µL (range, 3.8 - 27,700) in patients with ongoing responses at 12 months, 202.6 cells/µL (range, 1.6 - 2589.5) and 2312.3 cells/µL (range, 19.0 - 27,200) in patients who were relapsed at 12 months, and 0.4 cells/µL (range, 0.2 - 95.9) and 5.5 cells/µL (range, 1.8 - 1089.1) in nonresponders. Of the 57 efficacy-evaluable patients with data available, 84% had B cells detectable by flow cytometry at baseline. Of those in ongoing responses at 12 months, 10 of 26 patients (38%) with evaluable samples had B cells detectable at 3 months, and 10 of 18 (56%) had detectable B cells at 12 months; gene-marked CAR T cells were no longer detectable at 12 months in 5 of 28 evaluable patients (17%). Conclusions: The ZUMA-2 study continues to demonstrate substantial and durable clinical benefit of KTE-X19 therapy with manageable safety in patients with R/R MCL. Within this patient population, which lacks curative treatment options, most patients achieved durable CR, and no new safety signals were reported. Although early CAR T cell expansion was higher in patients who achieved an objective response, those who later relapsed showed elevated CAR T cell levels pointing to alternate mechanisms of secondary treatment failure in MCL. Disclosures Wang: Verastem: Research Funding; Molecular Templates: Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Dava Oncology: Honoraria; Targeted Oncology: Honoraria; VelosBio: Research Funding; BioInvent: Research Funding; Juno: Consultancy, Research Funding; OncLive: Honoraria; Pulse Biosciences: Consultancy; Loxo Oncology: Consultancy, Research Funding; Guidepoint Global: Consultancy; OMI: Honoraria, Other: Travel, accommodation, expenses; Nobel Insights: Consultancy; Acerta Pharma: Research Funding; Oncternal: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; InnoCare: Consultancy; Beijing Medical Award Foundation: Honoraria; Lu Daopei Medical Group: Honoraria. Munoz:Merck: Research Funding; Portola: Research Funding; Incyte: Research Funding; AbbVie: Consultancy, Speakers Bureau; Genentech/Roche: Research Funding, Speakers Bureau; AstraZeneca: Speakers Bureau; Verastem: Speakers Bureau; Acrotech/Aurobindo: Speakers Bureau; Innovent: Consultancy; Fosunkite: Consultancy; Beigene: Consultancy, Speakers Bureau; Alexion: Consultancy; Juno/Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Millenium: Research Funding. Goy:MD Anderson: Research Funding; Regional Cancer Care Associates/OMI: Current Employment; Xcenda: Consultancy; AbbVie: Research Funding; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Hackensack UMC and University of Nebraska: Research Funding; Infinity Verastem: Research Funding; Morphosys: Research Funding; Karyopharm: Research Funding; Infinity: Research Funding; Constellation: Research Funding; Genentech/Roche: Research Funding; CALBG: Research Funding; Bayer: Research Funding; PracticeUpdate Oncology: Consultancy; RCCA/OMI: Current Employment. Locke:Wugen: Consultancy; GammaDelta Therapeutics: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Calibr: Consultancy; Allogene: Consultancy; Cellular Biomedicine Group: Other: Consultancy with grant options. Hill:Genentech: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding. Timmerman:Corvus: Current equity holder in publicly-traded company; Marker Therapeutics: Current equity holder in publicly-traded company; Bluebird Bio: Current equity holder in publicly-traded company; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Immune Design: Honoraria; Celldex Therapeutics: Consultancy; BMS: Other: Travel support, Research Funding; Spectrum Pharmaceuticals: Research Funding; Merck: Research Funding; Valor: Research Funding; Genmab: Current equity holder in publicly-traded company. Holmes:Texas Oncology PA: Current Employment; Gilead/Kite, Celgene/Juno, Rigel, Karyopharm, Janssen, Dova: Consultancy; Gilead/Kite, Novartis, Autolus, Celgene/Juno/bluebird, Genentech, Inc., Rigel, Janssen, Unum, ADC Therapeutics, Seattle Genetics, Incyte, Verastem: Research Funding; Kite, Karyopharm, Seattle Genetics, Rigel, Dova: Speakers Bureau. Jaglowski:CRISPR: Consultancy; Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Flinn:Karyopharm Therapeutics: Research Funding; AstraZeneca: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Vincera Pharma: Consultancy; Iksuda Therapeutics: Consultancy; Janssen: Consultancy, Research Funding; Agios: Research Funding; ArQule: Research Funding; Infinity Pharmaceuticals: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Forty Seven: Research Funding; Great Point Partners: Consultancy; Pfizer: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Novartis: Research Funding; Nurix Therapeutics: Consultancy; Curis: Research Funding; MorphoSys: Consultancy, Research Funding; Juno Therapeutics: Consultancy, Research Funding; Incyte: Research Funding; Acerta Pharma: Research Funding; Genentech, Inc.: Research Funding; Gilead Sciences: Consultancy, Research Funding; F. Hoffmann-La Roche: Research Funding; AbbVie: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; IGM Biosciences: Research Funding; TG Therapeutics: Consultancy, Research Funding; Trillium Therapeutics: Research Funding; Triphase Research & Development Corp.: Research Funding; Verastem: Consultancy, Research Funding; Yingli Pharmaceuticals ≠: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Johnson & Johnson: Other; Teva: Research Funding; Seattle Genetics: Consultancy, Research Funding; Portola Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Merck: Research Funding; Celgene: Research Funding; Calithera Biosciences: Research Funding; BeiGene: Consultancy, Research Funding; Loxo: Research Funding; Kite Pharma: Consultancy, Research Funding; Curio Science: Consultancy. McSweeney:Fred Hutchinson: Patents & Royalties; Colorado Blood Cancer Institute: Current Employment; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau. Miklos:Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Miltenyi Biotec: Research Funding. Pagel:Gilead, Pharmacyclics LLC, an AbbVie Company, and AstraZeneca: Consultancy. Kersten:Novartis: Consultancy, Honoraria, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: travel support; Celgene: Research Funding; Roche: Research Funding; Takeda: Research Funding; Miltenyi: Consultancy, Honoraria, Other: travel support. Milpied:Celgene: Other: Travel support; Gilead Sciences: Other: consultancy or advisory role; Janssen: Honoraria; Sandoz: Honoraria, Other: consultancy or advisory role; Astellas: Honoraria; Roche: Honoraria, Other: Travel support. Fung:Takeda: Honoraria, Other: speakers' bureau, travel support; Sanotif: Honoraria, Other: speakers' bureau, travel support; Genentech: Honoraria, Other: speakers' bureau, travel support; AbbVie: Honoraria, Other: speakers' bureau, travel support; Kite, a Gilead Company: Honoraria, Other: speakers' bureau, travel support; AstraZeneca: Honoraria, Other: speakers' bureau, travel support; Janssen Oncology: Honoraria, Other: speakers' bureau, travel support. Topp:Amgen, Boehringer Ingelheim, KITE, Regeneron, Roche: Research Funding; Amgen, KITE, Novartis, Regeneron, Roche: Consultancy. Houot:Janssen: Honoraria; Gilead: Other: Personal fees; Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Beitinjaneh:Jazz: Other: speaker's bureau; Kite, a Gilead Company: Honoraria, Other: consulting or advisory role, speaker's bureau, ; ATARA: Research Funding; Gilead: Research Funding. Peng:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Zheng:Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Rossi:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Murugappan:Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Kloos:Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company. Reagan:Curis: Consultancy; Seattle Genetics: Research Funding; Kite, a Gilead Company: Consultancy.

Background: Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for the treatment of patients (pts) with relapsed/refractory large B cell lymphoma (LBCL) with ≥ 2 prior systemic therapies. ZUMA-1 is the multicenter, single-arm, registrational Phase 1/2 study of axi-cel in pts with refractory LBCL. In a 2-year analysis of ZUMA-1 (median follow-up, 27.1 months; N=101), axi-cel demonstrated objective response, complete response (CR), and ongoing response rates of 83%, 58%, and 39%, respectively (Locke et al. Lancet Oncol. 2019). Here, we present additional survival follow up and recovery of normal, polyclonal B cells from ongoing responders in ZUMA-1. Methods: Eligible pts with refractory large B cell lymphoma (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, transformed follicular lymphoma) underwent leukapheresis at enrollment and subsequently received low-dose conditioning chemotherapy (fludarabine and cyclophosphamide) followed by a target dose of 2 × 106 anti-CD19 CAR T cells/kg (Neelapu et al. NEJM. 2017; NCT02348216). The primary endpoint was objective response rate (ORR), and the first response assessment was 4 weeks post infusion. Response assessments were performed per protocol up to 24 months or disease progression, whichever occurred first. For pts in ongoing response beyond Month 24, response assessments continued per institutional standard-of-care (SOC). Blood levels of CAR T cells were quantified using polymerase chain reaction and B cells were characterized using flow cytometry in pts with ongoing responses and evaluable samples. Results: A total of 111 pts were enrolled, and axi-cel was administered to 101 pts. As previously reported in the ZUMA-1 2-year analysis, among pts who received axi-cel, the median time from axi-cel infusion to both objective response and CR was 1.0 month (range, 1 - 12 months; Locke et al. Lancet Oncol 2019). When the entire enrolled population (N = 111) was included on an intent-to-treat basis, the median manufacturing time was 17 days (range, 14 - 51; n = 110 as manufacturing was not feasible for 1 pt). Additionally, among the 111 pts, the median time from enrollment/leukapheresis to objective response and CR was 1.7 months (range, 0.7 - 12.9) and 1.9 months (range, 0.7 - 13.3), respectively. Responses have been durable, and with a minimum of 3 years of follow-up (median, 39.1 months), the median overall survival (OS) was 25.8 months, and the 3-year OS rate was 47%. Importantly, no axi-cel-related secondary malignancies have been reported. As previously reported, pts in ongoing response after 2 years had significantly greater peak CAR T cell expansion in blood 7 - 14 days after axi-cel infusion than did those with relapse (P = 0.014) or no response (P = 0.0003; Locke et al. Lancet Oncol 2019). Blood samples from 22 pts in ongoing response (per institutional SOC) at ≥ 3 years were available for analysis of CAR T cells and evaluation of B cell recovery. All evaluable pts had detectable B cells in blood at 3 years post axi-cel. Notably, 91% of pts in ongoing response at 3-year follow-up demonstrated recovery of polyclonal B cells measured by presence of both kappa and lambda light chains on non-malignant CD19+CD20+ B cells. The median kappa-lambda ratio of 1.6 and relative levels of key B cell subsets, including memory and naive B cell immunophenotypes, suggested reconstitution of B cell repertoire, consistent with published data from healthy individuals (Deneys et al. J Immunol Methods 2001; Scott et al. J Clin Pathol 2018). Additionally, 15/22 (68%) had both minimal levels of detectable CAR gene-marked cells and detectable polyclonal B cells in blood. Altogether, these findings support the hypothesis that persistence of functional CAR T cells is not necessary for durable remissions of LBCL. Overall survival and translational findings with ≥ 4 years of follow-up will be presented. Conclusions: Axi-cel produced rapid responses and longterm disease control in pts with refractory LBCL. Most responses occurred by the first assessment, and the brief time elapsed between enrollment and response supports both the speed and success of manufacturing. Furthermore, axi-cel-treated pts with ongoing responses at ≥ 3 years showed evidence of restoration of a normal B cell compartment and clearance of functional CAR T cells, a critical component of the long-term safety of CD19-directed CAR T cell therapies. Disclosures Locke: Kite, a Gilead Company: Consultancy, Research Funding; Wugen: Consultancy; Calibr: Consultancy; Allogene: Consultancy; Cellular Biomedicine Group: Other: Consultancy with grant options; GammaDelta Therapeutics: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. Ghobadi:Celegene: Consultancy; Wugen: Consultancy; Atara: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; EUSA: Consultancy. Miklos:Novartis: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Oluwole:Pfizer: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Spectrum Pharmaceuticals: Consultancy; Bayer: Consultancy. Lin:Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Merck: Research Funding; Vineti: Consultancy. Hill:Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding. Timmerman:Merck: Research Funding; Corvus: Current equity holder in publicly-traded company; Marker Therapeutics: Current equity holder in publicly-traded company; Immune Design: Honoraria; Celldex Therapeutics: Consultancy; BMS: Other: Travel support, Research Funding; Spectrum Pharmaceuticals: Research Funding; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Genmab: Current equity holder in publicly-traded company; Valor: Research Funding. Deol:Novartis: Consultancy; Kite, a Gilead Company: Consultancy. Reagan:Kite, a Gilead Company: Consultancy; Curis: Consultancy; Seattle Genetics: Research Funding. Stiff:Kite, a Gilead Company: Research Funding; Delta-Fly: Research Funding; Gamida Cell: Research Funding; Atara: Research Funding; Unum: Research Funding; Macrogenics: Research Funding; Amgen: Research Funding. Flinn:Celgene: Research Funding; TG Therapeutics: Consultancy, Research Funding; Trillium Therapeutics: Research Funding; Curio Science: Consultancy; Merck: Research Funding; Constellation Pharmaceuticals: Research Funding; BeiGene: Consultancy, Research Funding; ArQule: Research Funding; Kite Pharma: Consultancy, Research Funding; Genentech, Inc.: Research Funding; Pfizer: Research Funding; Calithera Biosciences: Research Funding; Agios: Research Funding; Karyopharm Therapeutics: Research Funding; AstraZeneca: Consultancy, Research Funding; Forty Seven: Research Funding; Forma Therapeutics: Research Funding; Loxo: Research Funding; F. Hoffmann-La Roche: Research Funding; Incyte: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Novartis: Research Funding; MorphoSys: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Yingli Pharmaceuticals ≠: Consultancy, Research Funding; Johnson & Johnson: Other; Roche: Consultancy, Research Funding; Vincera Pharma: Consultancy; Gilead Sciences: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; Great Point Partners: Consultancy; Curis: Research Funding; Nurix Therapeutics: Consultancy; Portola Pharmaceuticals: Research Funding; Acerta Pharma: Research Funding; Juno Therapeutics: Consultancy, Research Funding; Unum Therapeutics: Consultancy, Research Funding; Infinity Pharmaceuticals: Research Funding; IGM Biosciences: Research Funding; Takeda: Consultancy, Research Funding; Teva: Research Funding; Seattle Genetics: Consultancy, Research Funding; Triphase Research & Development Corp.: Research Funding; Verastem: Consultancy, Research Funding. Farooq:Kite, a Gilead Company: Honoraria. Goy:COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Karyopharm: Research Funding; Genentech/Roche: Research Funding; Constellation: Research Funding; Bayer: Research Funding; CALBG: Research Funding; PracticeUpdate Oncology: Consultancy; RCCA/OMI: Current Employment; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Celgene: Honoraria, Research Funding; Hackensack UMC and University of Nebraska: Research Funding; Infinity: Research Funding; Xcenda: Consultancy; Infinity Verastem: Research Funding; Morphosys: Research Funding; AbbVie: Research Funding; MD Anderson: Research Funding; Regional Cancer Care Associates/OMI: Current Employment; Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding. McSweeney:Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Colorado Blood Cancer Institute: Current Employment; Fred Hutchinson: Patents & Royalties. Munoz:Juno/Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Alexion: Consultancy; Beigene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Acrotech/Aurobindo: Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Verastem: Speakers Bureau; AstraZeneca: Speakers Bureau; Genentech/Roche: Research Funding, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Merck: Research Funding; Portola: Research Funding; Incyte: Research Funding; Millenium: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau. Siddiqi:Oncternal: Research Funding; TG Therapeutics: Research Funding; Janssen: Speakers Bureau; Seattle Genetics: Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Juno: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Rossi:Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Bot:Kite, a Gilead Company: Current Employment; Gilead Sciences: Consultancy, Current equity holder in publicly-traded company, Other: Travel support . Zheng:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Vezan:Merck: Current equity holder in publicly-traded company; Abbvie: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment, Honoraria, Other: Travel support. Bashir:Kite, a Gilead Company: Current Employment; OmniacPharmConsult Ltd: Current Employment, Current equity holder in private company. Kim:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Chu:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company; Amgen: Current equity holder in publicly-traded company; Celgene: Current equity holder in publicly-traded company. Neelapu:N/A: Other; Takeda Pharmaceuticals: Patents & Royalties; Acerta: Research Funding; Karus Therapeutics: Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Unum Therapeutics: Other, Research Funding; Calibr: Other; Kite, a Gilead Company: Other: personal fees, Research Funding; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Novartis: Other: personal fees; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Allogene Therapeutics: Other: personal fees, Research Funding; Adicet Bio: Other; Legend Biotech: Other; Precision Biosciences: Other: personal fees, Research Funding; Incyte: Other: personal fees; Cell Medica/Kuur: Other: personal fees.