Timmerman, John M.

Abstract Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Although patients with FL have high response rates to therapy, most develop increasingly resistant disease. In addition, transformation into an aggressive lymphoma is associated with unfavorable outcomes. Many novel agents are under investigation, and early clinical data are encouraging. Aligning treatment with the underlying tumor biology and sequencing of therapies remain key clinical challenges. At the Lymphoma Research Foundation’s biannual 2024 Follicular Lymphoma Scientific Workshop, experts convened to discuss the role of chemotherapy in the context of new therapies, the impact of early progression on treatment sequencing, novel end points in clinical trials, disease biology and the tumor microenvironment, and new treatments on the horizon. This report focuses on updates in FL biology, first-line treatment, the role of progression of disease in 24 months, clinical trial design, and redefining cure in FL.

Introduction: Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved in the US and EU for treatment of adults with R/R MCL (after ≥2 prior therapies in EU) based on a high objective response rate (ORR; 93%; 67% complete response [CR] rate) in pts who received the pivotal dose (2×106 anti-CD19 CAR T cells/kg; Cohort 1; N=60) in ZUMA-2 (NCT02601313; Wang et al, N Engl J Med 2020). After ~4 years (y) of median follow-up, Brexu-cel demonstrated a median overall survival (OS) of 46.4 months (mo) in 68 pts with R/R MCL in Cohort 1 (Goy et al. ASH 2023). Cohort 2 was established to assess a lower dose (0.5 x 106 anti-CD19 CAR T cells/kg); however, the risk/benefit ratio of the Cohort 1 dose was deemed the optimal dose before Cohort 2 reached full enrollment. Here we report primary outcomes of Cohort 2 and 5-y outcomes of Cohorts 1 and 2. Methods: Pts with R/R MCL and ≤5 prior therapies including a BTKi received optional bridging therapy (protocol-defined), lymphodepleting chemotherapy, and 1 infusion of brexu-cel. The primary endpoint was ORR (CR + partial response [PR]) per Lugano classification (Cheson et al. J Clin Oncol. 2014) by independent radiology review committee (IRRC) assessment. Key secondary endpoints were duration of response (DOR), best objective response (BOR), progression-free survival (PFS), OS, and safety. After ≥24 mo of assessment, pts could transition to long-term follow-up (LTFU), NCT05041309, where they were monitored for late-onset targeted/serious adverse events (AEs) possibly related to brexu-cel, presence of replication-competent retrovirus (RCR), and/or insertional mutagenesis. Descriptive statistics are reported herein. Results: As of the primary analysis data cutoff date, July 24, 2019, 17 pts enrolled in Cohort 2, 14 (82%) of whom were treated with brexu-cel with median follow-up of 16.0 mo (range, 13.9-18.0). Pt characteristics for Cohort 2 (N=14) were similar to Cohort 1; median (range) age and number or prior therapies was 61.5 y (52-73) and 3 (2-5); 100% US-treated, 79% male, 71% extranodal disease, 50% intermediate or high s-MIPI scores, 50% refractory to last therapy, and 43% had prior autologous stem cell transplantation. ORR was 93% (95% CI, 66.1-99.8) per IRRC; 64% had a CR (95% CI, 35.1-87.2), 29% had a PR (95% CI, 8.4-58.1) and 1 pt was not assessed. All 14 pts had ≥1 AE of any grade (Gr), with Gr ≥3 AEs occurring in 93% of pts; the most common being hypotension (50%), white blood cell count decrease (50%), anemia (43%), and neutrophil count decrease (43%). Rates of Gr ≥3 cytokine release syndrome (CRS) and neurological events were 7% and 43%, respectively. As of April 1, 2024, median follow-up (range) for Cohort 1 and 2 was 67.8 mo (58.2-88.6; N=68) and 72.3 mo (70.1-74.3; N=14), respectively. In Cohort 1, 24 pts were still alive (35%; 2 withdrew consent and 1 lost to follow up) and 44 pts died (65%). In Cohort 2, 8 pts were still alive (57%; 2 withdrew consent and 1 lost to follow up) and 6 pts died (43%). A total of 27 pts (Cohort 1, n=23; Cohort 2, n=4) enrolled in the LTFU study by data cutoff with a median follow-up time of 70.2 mo (range, 58.2-88.6). Median (95% CI) investigator-assessed DOR and PFS were 36.5 mo (17.7-48.9; n=60; 17 patients in ongoing response, all CR) and 25.3 mo (12.7-46.6; N=68) in Cohort 1; and 57.5 mo (4.7-not estimable [NE]; n=12; 3 pts in ongoing response, all CR) and 29.5 mo (3.3-NE; N=14) in Cohort 2. Median OS (95% CI) and 60-mo OS rates (95% CI) were 46.5 mo (24.9- 60.2) and 38.5% (26.7-50.1) in Cohort 1; and not reached (9.4-NE) and 53.6% (23.8-76.2) in Cohort 2. One pt had 3 ongoing AEs on LTFU, hypogammaglobulinemia and 2 viral infections that arose prior to LTFU. Two pts died on LTFU, both due to progressive disease; no new secondary malignancies or RCR cases were reported. Conclusions: Consistent with Cohort 1, brexu-cel demonstrated a high ORR, durable responses, and an expected safety profile in pts with R/R MCL in Cohort 2 despite the lower dose. However, small sample size limits interpretation of these results. With >5 y of median follow-up, pts in Cohort 1 and 2 continued to experience durable responses with high 60-mo OS rates. No new safety signals were detected and no secondary malignancies or RCR cases were reported in LTFU. Additionally, ZUMA-2 results are consistent with real-world outcomes of brexu-cel in the post BTKi R/R MCL setting (89% ORR and 81% CR rate; Wang Y, et al. J Clin Oncol. 2023). These results support the continued use of brexu-cel in R/R MCL.

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

Abstract Background: ZUMA-1 is a pivotal, multicenter trial of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, for the treatment of patients with refractory, aggressive NHL. The objective response rate (ORR) was 82% with a 54% rate of complete response and 44% of responses were ongoing at the time of the primary analysis (Locke et al. AACR 2017. #9986). Grade ≥ 3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 13% and 28% of patients, respectively. A safety expansion cohort was added to further characterize mechanisms underlying CRS and NE associated with CAR T cell therapy and to evaluate the impact of prophylactic use of tocilizumab and levetiracetam on the rates of these adverse events (AEs). Methods: Patients (≥ 18 years) must have had an Eastern Cooperative Oncology Group performance status of 0-1 and refractory or relapsed transplant ineligible disease. Patients received low-dose conditioning of 500 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine for 3 days followed by axi-cel at a target dose of 2 × 106 CAR T cells/kg. Patients also received prophylactic treatment with 750 mg of levetiracetam twice a day on day 0 and 8 mg/kg of tocilizumab on day 2 post axi-cel infusion. To evaluate the mechanisms of NE, paired serum and cerebrospinal fluid (CSF) were obtained for all patients prior to conditioning chemotherapy and after axi-cel infusion (day 5). Results: As of April 26, 2017, 31 patients received axi-cel. Median age was 51 years (range, 21-74), 52% were male, 65% had stage III-IV disease, 74% were refractory to ≥ second-line therapy, and 19% relapsed ≤ 12 months after autologous stem cell transplant. Most patients (97%) experienced at least 1 grade ≥ 3 AE. The most common grade ≥ 3 AEs were neutropenia/neutrophil count decreased (71%), anemia (55%), thrombocytopenia/platelet count decreased (52%), leukopenia/white blood cell count decreased (35%), febrile neutropenia (29%), encephalopathy (23%), and hypotension (23%). One patient (3%) experienced a grade ≥ 3 (grade 4) CRS. Grade 3 and 4 NE occurred in 29% and 6% of patients, respectively. One patient died of cerebral edema; there were no other deaths due to AE. Updated efficacy, safety, subgroups, and paired blood/serum/CSF biomarker associative analyses will be presented. Conclusions : Early use of tocilizumab may reduce the incidence of severe CRS but not NE in patients treated with CAR T cell therapy. These data provide evidence that the underlying pathophysiology of NE may differ from that of CRS. Understanding the mechanisms of NE may help to further improve the benefit:risk profile for CAR T cell therapy. Drs Locke and Neelapu contributed equally to this work. Disclosures Locke: Kite Pharma: Consultancy; Cellular Biomedicine Group Inc: Consultancy. Neelapu: Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jacobson: Pharmacyclics, LLC: Consultancy; Kite Pharma: Consultancy. Braunschweig: Kite Pharma: Equity Ownership. Oluwole: Kite Pharma: Consultancy. Siddiqi: Seattle Genetics: Speakers Bureau; Juno: Other: Steering committee for JCAR017; Pharmacyclics, an AbbVie Company: Other: Steering committee for ibrutinib, Speakers Bureau. Timmerman: Celgene: Consultancy; Seattle Genetics: Consultancy; Kite Pharma: Research Funding; ImmuneGene: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Genmab: Consultancy, Equity Ownership. Reagan: Seattle Genetics: Research Funding. Bot: Kite Pharma: Employment, Equity Ownership. Rossi: Kite Pharma: Employment, Equity Ownership. Sherman: Kite Pharma: Employment, Equity Ownership. Navale: Kite Pharma: Employment, Equity Ownership. Jiang: Kite Pharma: Employment, Equity Ownership. Aycock: Kite Pharma: Employment, Equity Ownership. Elias: Kite Pharma: Employment, Equity Ownership. Wiezorek: Kite Pharma: Employment, Equity Ownership. Go: Kite Pharma: Employment, Equity Ownership. Miklos: Pharmacyclics, LLC: Consultancy, Other: Travel expenses, Patents & Royalties, Research Funding; Kite Pharma: Consultancy, Other: Travel expenses, Research Funding; Adaptive Biotechnologies: Consultancy, Other: Travel expenses; Roche: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Janssen: Consultancy, Honoraria, Other: Travel expenses; Sanofi: Honoraria.

Abstract Background: Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is approved for the treatment of pts with relapsed/refractory LBCL with ≥ 2 prior systemic therapies. In the 2-year analysis of ZUMA-1 (NCT02348216), the multicenter, single-arm phase 1/2 study evaluating axi-cel in pts with refractory LBCL, the objective response rate (ORR) was 83%, including a complete response (CR) rate of 58%; 39% of pts had ongoing response with a median follow-up of 27.1 months (Locke et al. Lancet Oncol. 2019). EFS is emerging as a robust surrogate endpoint for OS in hematologic malignancies. A recent systematic analysis demonstrated a linear correlation between EFS and OS in pts with diffuse LBCL after first-line immunochemotherapy (Zhu et al. Leukemia. 2020). Here, we report updated survival findings from the phase 2 portion of ZUMA-1 after 4 years of follow-up, including an evaluation of the association of OS with EFS. Methods: Eligible pts had refractory LBCL (diffuse LBCL, primary mediastinal B cell lymphoma, transformed follicular lymphoma). After leukapheresis at enrollment, pts received low-dose conditioning chemotherapy (fludarabine and cyclophosphamide) followed by a target dose of 2×10 6 anti-CD19 CAR T cells/kg (Neelapu et al. N Engl J Med. 2017). The primary endpoint was ORR, with the first response assessment occurring 4 weeks following infusion. Additional endpoints included safety and translational evaluations. An exploratory analysis of OS by EFS at 12 and 24 months was performed. EFS was defined as the time from axi-cel infusion until disease progression, initiation of new lymphoma therapy (excluding stem cell transplant), or death from any cause. Comparisons of OS by EFS outcomes were analyzed via Kaplan-Meier estimates. Results: Of 111 enrolled pts, axi-cel was administered to 101 pts. As of August 11, 2020, median follow-up was 51.1 months. With over 4 years of follow-up, median OS was 25.8 months, and the 4-year OS rate was 44%. Median EFS in pts treated with axi-cel was 5.7 months, with a 12-month EFS rate of 43% (95% CI, 33-52) and a 24-month EFS rate of 38% (95% CI, 28-47). In pts with an EFS event by Month 12 (EFS12; n=57) vs those without EFS12 (n=44), 4-year OS rates were 7% (95% CI, 2-16) vs 91% (95% CI, 78-97), respectively. Among the 17 pts with EFS12 who were alive at Month 12, 13 (76%) died by Month 48, while among the 44 pts alive at Month 12 without EFS12, 4 (9%) died by Month 48. In pts with an EFS event by Month 24 (EFS24; n=62) vs those without EFS24 (n=39), 4-year OS rates were 13% (95% CI, 6-23) vs 92% (95% CI, 78-98), respectively. Among the 12 pts with EFS24 who were alive at Month 24, 4 (33%) died by Month 48, while among the 39 pts alive at Month 24 without EFS24, 3 (8%) died by Month 48. Since the 2-year analysis (Locke et al. Lancet Oncol. 2019), there have been no new safety signals reported, including no new serious adverse events, no axi-cel-related secondary malignancy, and no confirmed cases of replication-competent retrovirus. Overall, 26 pts received subsequent anti-cancer therapy; median time to next therapy was 8.7 months (range, 0.3 - 53.8). Immunoglobulin therapy was administered to 38 (38%) pts. Two pts in axi-cel-induced remission received allogeneic stem cell transplant; 1 pt was in CR and 1 pt was in partial response. Among treated pts, 58 (57%) have died, primarily due to progressive disease (46%; n=46), followed by other reasons (7%; n=7), adverse events (4%; n=4), and secondary malignancy (myelodysplastic syndrome, with onset on Day 574) unrelated to axi-cel (1%; n=1). Among pts without EFS12 and without EFS24, 1 pt each (2% and 3%, respectively) died due to disease progression >24 months following axi-cel infusion; >36 months, 2 pts each (5% for both) died due to disease progression (1 pt each [2% and 3%]) and other reasons (1 pt each [2% and 3%]. One pt (2%) without EFS12 died due to disease progression between 12 and 24 months. Updated findings with ≥5 years of follow-up, including translational correlations, will be presented. Conclusion: In this long-term survival analysis of ZUMA-1 with ≥4 years of follow-up, axi-cel demonstrated longer OS in pts without EFS events at Month 12 and Month 24 vs pts with events at these timepoints. These data support the use of EFS as a surrogate endpoint for long-term OS in refractory LBCL, and the relationship between EFS and 5-year OS will be presented. Disclosures Jacobson: Nkarta: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Axis: Speakers Bureau; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; Clinical Care Options: Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Lonza: Consultancy, Honoraria, Other: Travel support; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; Humanigen: Consultancy, Honoraria, Other: Travel support. Locke: Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Janssen: Consultancy, Other: Scientific Advisory Role; Gerson Lehrman Group: Consultancy; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Emerging Therapy Solutions: Consultancy; Takeda: Consultancy, Other; Wugen: Consultancy, Other; EcoR1: Consultancy; Umoja: Consultancy, Other; Cowen: Consultancy; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding. Ghobadi: Atara: Consultancy; Amgen: Consultancy, Research Funding; Wugen: Consultancy; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Miklos: Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Patents & Royalties; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy. Oluwole: Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Pfizer: Consultancy; Curio Science: Consultancy. Lin: Gamida Cell: Consultancy; Legend: Consultancy; Juno: Consultancy; Takeda: Research Funding; Merck: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Vineti: Consultancy; Sorrento: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Hill: Celgene (BMS): Consultancy, Honoraria, Research Funding; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Gentenech: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Epizyme: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Timmerman: Spectrum Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Marker Therapeutics: Current equity holder in publicly-traded company; Corvus: Current equity holder in publicly-traded company; Genmab: Current equity holder in publicly-traded company; Merck: Research Funding; TG Therapeutics: Current equity holder in publicly-traded company. Deol: Kite, a Gilead Company: Consultancy. Reagan: Seagen: Research Funding; Kite, a Gilead Company: Consultancy; Genentech: Research Funding; Curis: Consultancy. Stiff: Karyopharm: Consultancy, Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; Kite, a Gilead Company: Research Funding; Amgen: Research Funding; Macrogenics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Research Funding; Gamida Cell: Research Funding; Seagen: Research Funding; Cellectar: Research Funding; Incyte: Research Funding; BioLineRX: Research Funding; Cellectar: Research Funding; Actinium: Research Funding; MorphoSys: Consultancy, Honoraria. Flinn: Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Farooq: Kite, a Gilead Company: Honoraria. Goy: MorphoSys: Honoraria, Other; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; OncLive Peer Exchange: Honoraria; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Michael J Hennessey Associates INC: Consultancy; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Medscape: Consultancy; Xcenda: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Genentech/Hoffman la Roche: Research Funding; Infinity/Verastem: Research Funding; Janssen: Research Funding; Rosewell Park: Consultancy; LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Xcenda: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Karyopharm: Research Funding; Phamacyclics: Research Funding; Constellation: Research Funding; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Muñoz: Bayer, Kite, a Gilead Company, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seagen, and Janssen, Millennium: Research Funding; Kite, a Gilead Company, Kyowa, Bayer, Pharmacyclics, Janssen, Seagen, Acrotech, Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/Bristol Myers Squibb, Genentech, and Roche: Speakers Bureau; Pharmacyclics, Abbvie, Bayer, Kite, a Gilead Company, Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa, Alexion, Beigene, Fosun Kite, Innovent, Seagen, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, and Servier: Consultancy; Targeted Oncology, OncView, Kyowa, Physicians' Education Resource, and Seagen: Honoraria; OncView: Honoraria; Kyowa Kirin: Honoraria; Physicians' Education Resource: Honoraria. Siddiqi: Oncternal: Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; TG Therapeutics: Research Funding. Shen: Atara: Current Employment, Current equity holder in publicly-traded company, Other: Leadership role, Patents & Royalties; Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment, Other: Leadership role, Patents & Royalties. Bot: Kite, a Gilead Company: Current Employment; Gilead Sciences: Consultancy, Current equity holder in publicly-traded company, Other: Travel support. Dong: GliaCure/Tufts: Consultancy, Patents & Royalties; Gilead: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Singh: Kite, a Gilead Company: Current Employment. Spooner: Kite, a Gilead Company: Current Employment; Gilead: Current equity holder in publicly-traded company. Karalliyadda: Kite, a Gilead Company: Current Employment; Gilead: Current equity holder in publicly-traded company. Kim: Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Zheng: Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding.

Abstract Background: ZUMA-1 is the registrational Phase 1/2 study of axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pts with refractory LBCL. In ZUMA-1 Cohorts 1+2 (C1+2; N=101), rates of Grade (Gr) ≥3 cytokine release syndrome (CRS) and neurologic events (NEs) were 13% and 28%, respectively, at the 6-mo primary analysis; the objective response rate (ORR) was 82% (54% complete response [CR]; Neelapu et al. NEJM. 2017). ZUMA-1 safety management C6 assessed whether prophylactic and earlier corticosteroids and/or tocilizumab could reduce incidence and severity of CRS and NEs. With a median follow-up of 8.9 mo (N=40) for C6, there were no Gr ≥3 CRS, a low rate of Gr ≥3 NEs (13%), and high response rates (Oluwole et al. BJH. 2021). Here, we present a 1-yr updated analysis of C6 supported by propensity score matching (PSM) analysis to compare outcomes for pts in C6 vs C1+2. Methods: Eligible pts could receive optional bridging therapy after leukapheresis. Pts received conditioning chemotherapy for 3 d prior to a single axi-cel infusion. Pts received once-daily oral dexamethasone 10 mg on Days 0 (before axi-cel), 1, and 2; corticosteroids and/or tocilizumab for adverse event (AE) management were given earlier vs C1+2. The primary endpoints were incidence and severity of CRS and NEs. Other endpoints included efficacy outcomes and biomarker analyses. To ensure comparability for pts in C6 and C1+2, an exploratory PSM analysis was performed after balancing for key baseline disease characteristics (tumor burden, IPI score, no. of prior lines of chemotherapy, disease stage, and LDH level). Results: As of December 16, 2020, the median follow-up time was 14.9 mo. Gr ≥3 AEs were reported in all 40 treated pts, and the most common were neutropenia (45%), neutrophil count decreased (33%), and white blood cell count decreased (23%). No Gr ≥3 CRS occurred. Gr ≥3 NEs were reported in 15% of pts. Median time to CRS and NE onset was 5 and 6 d, respectively, after axi-cel infusion. Infections of any grade occurred in 50% of pts (20% Gr ≥3). Since the 6-mo analysis, no new cases of CRS were observed. Four new axi-cel-related NEs occurred in 2 pts (pt 1: Gr 2 mental status changes and seizure-like phenomena both on Day 441; pt 2: Gr 1 dementia [occurred on Day 93 but was reported late] and Gr 5 toxic encephalopathy on Day 369 [resultant from a Gr 4 event that started on Day 351]). Two new infections of Gr 2 pneumonia and Gr 1 bronchitis were observed; the latter was axi-cel-related. One death due to progressive disease occurred. The investigator-assessed ORR was 95% (80% CR). Median DOR, PFS, and OS were not reached. Kaplan-Meier estimates of the 12-mo DOR, PFS, and OS rates were 60%, 63%, and 82%, respectively. At data cutoff, 53% of pts were in ongoing response. Median peak CAR T-cell levels were comparably high in pts with ongoing response and relapse (64 cells/µL [n=21] and 66 cells/µL [n=15], respectively) at 12 mo and considerably lower in nonresponders (18 cells/µL [n=2]). In all, 32 matched pts each in C6 and C1+2 were identified during PSM analysis; 8 pts from C6 were not included due to nonavailability of matched pts in C1+2. No Gr ≥3 CRS was observed in C6 vs 13% of pts in C1+2. Incidence of Gr ≥3 NEs was comparable in C6 and C1+2 (19% and 22%, respectively), with median time to onset of 12 d in C6 vs 7 d in C1+2. The ORR was 94% in both C6 and matched C1+2 (75% and 78% CR rates, respectively); 47% and 59% of pts were in ongoing response at 12 mo. The Kaplan-Meier estimate of the 12-mo PFS rate was 61% in both C6 and matched C1+2. Median peak CAR T-cell levels were 65 and 43 cells/µL, respectively, in C6 and C1+2. Serum levels of inflammatory biomarkers associated with CAR T-cell treatment-related AEs (IFN-γ, IL-2, GM-CSF, and ferritin) were lower in C6 vs C1+2. Median cumulative corticosteroid dose including prophylaxis was 1252 mg in C6 (n=32) and 7418 mg in C1+2 (n=6). Conclusion: With ≥1-y follow-up, prophylactic and earlier corticosteroid and/or tocilizumab intervention continued to demonstrate a manageable safety profile, absence of new safety signals, and high, durable response rates, which was corroborated by PSM analysis. Although fewer pts in C1+2 received corticosteroids after matching, the median cumulative corticosteroid dose was 4-fold lower in C6 vs C1+2. These findings suggest that the C6 AE management strategy can improve long-term safety of axi-cel in R/R LBCL without compromising durability of responses. Disclosures Oluwole: Pfizer: Consultancy; Curio Science: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Forcade: Jazz: Other: Travel Support, Speakers Bureau; MSD: Other: Travel Support; Gilead: Other: Travel Support, Speakers Bureau; Novartis: Consultancy, Other: Travel Support, Speakers Bureau. Muñoz: Targeted Oncology: Honoraria; Seagen: Consultancy, Honoraria, Speakers Bureau; Physicians' Education Resource: Honoraria; Kyowa Kirin: Consultancy, Honoraria, Speakers Bureau; OncView: Honoraria; Pharmacyclics: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Kite, a Gilead Company: Consultancy, Speakers Bureau; Pfizer: Consultancy; Janssen: Consultancy, Speakers Bureau; Juno/Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Alexion: Consultancy; BeiGene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Debiopharma: Consultancy; Karyopharm: Consultancy; Genmab: Consultancy; ADC Therapeutics: Consultancy; Epizyme: Consultancy; Servier: Consultancy; Acrotech: Speakers Bureau; Verastem: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol Myers Squibb: Speakers Bureau; Genentech: Speakers Bureau; Aurobindo: Speakers Bureau. de Guibert: Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Bartlett: Roche/Genentech: Consultancy; Seagen: Consultancy, Research Funding; Autolus: Research Funding; Bristol Myers Squibb: Research Funding; Celgene: Research Funding; Forty Seven: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; Merck: Research Funding; Millennium: Research Funding; Pharmacyclics: Research Funding; ADC Therapeutics: Consultancy, Research Funding. Lin: Juno: Consultancy; Takeda: Research Funding; Gamida Cell: Consultancy; Vineti: Consultancy; Merck: Research Funding; Sorrento: Consultancy; Legend: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Deol: Kite, a Gilead Company: Consultancy. McSweeney: Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; Autolus: Research Funding; Allovir: Research Funding. Goy: Acerta: Consultancy, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Xcenda: Consultancy, Honoraria; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; MorphoSys: Honoraria, Other; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; LLC(Targeted Oncology): Consultancy; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; OncLive Peer Exchange: Honoraria; Rosewell Park: Consultancy; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Celgene: Consultancy, Honoraria, Research Funding; Xcenda: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; Michael J Hennessey Associates INC: Consultancy; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Medscape: Consultancy; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Hoffman la Roche: Consultancy; Infinity/Verastem: Research Funding; Genentech/Hoffman la Roche: Research Funding; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Janssen: Membership on an entity's Board of Directors or advisory committees; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Janssen: Research Funding; Karyopharm: Research Funding; Phamacyclics: Research Funding; Constellation: Research Funding; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Kersten: Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; BMS/Celgene: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel support. Jacobson: Nkarta: Consultancy, Honoraria; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; Humanigen: Consultancy, Honoraria, Other: Travel support; Lonza: Consultancy, Honoraria, Other: Travel support; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Other: Travel support; Axis: Speakers Bureau; Clinical Care Options: Speakers Bureau. Farooq: Kite, a Gilead Company: Honoraria. Minnema: Cilag: Consultancy; BMS: Consultancy; Janssen: Consultancy; Celgene: Other: Travel expenses; Kite/Gilead: Consultancy; Alnylam: Consultancy. Thieblemont: Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Timmerman: Spectrum Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; TG Therapeutics: Current equity holder in publicly-traded company; Marker Therapeutics: Current equity holder in publicly-traded company; Corvus: Current equity holder in publicly-traded company; Genmab: Current equity holder in publicly-traded company; Merck: Research Funding. Stiff: Macrogenics: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Research Funding; Seagen: Research Funding; Gamida Cell: Research Funding; Janssen: Research Funding; CRISPR Therapeutics: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Cellectar: Research Funding; Bristol Myers Squibb: Research Funding; Incyte: Research Funding; BioLineRX: Research Funding; Cellectar: Research Funding; MorphoSys: Consultancy, Honoraria; Actinium: Research Funding. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. Tzachanis: Fate Therapeutics: Research Funding; Incyte: Research Funding; Genentech: Research Funding; Bristol Myers Squibb: Research Funding; Magenta: Consultancy; Kyowa Kirin: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; EUSA: Consultancy; Takeda: Consultancy, Speakers Bureau; Partner: Consultancy. Kim: Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Zheng: Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Shen: Gilead Sciences: Current equity holder in publicly-traded company; Atara: Current Employment, Current equity holder in publicly-traded company, Other: Leadership role, Patents & Royalties; Kite, a Gilead Company: Current Employment, Other: Leadership role, Patents & Royalties. Vardhanabhuti: Kite, a Gilead Company: Current Employment, Other: Travel support, Research Funding; Gilead Sciences: Current equity holder in publicly-traded company. Van Meerten: Kite, a Gilead Company: Honoraria; Janssen: Consultancy.

SummaryZUMA‐1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi‐cel), an autologous CD19‐directed chimaeric antigen receptor (CAR)‐T cell therapy, in refractory large B‐cell lymphoma. To reduce treatment‐related toxicity, several exploratory safety management cohorts were added to ZUMA‐1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end‐points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days −5 through −3), 2 × 106 CAR‐T cells/kg (day 0) and once‐daily oral dexamethasone [10 mg, day 0 (before axi‐cel) through day 2]. Forty patients received axi‐cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty‐eight per cent of patients did not experience CRS or NEs within 72 h of axi‐cel. With a median follow‐up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

Abstract Introduction: The phase 2 CheckMate 205 study (NCT02181738) of nivolumab (nivo) has demonstrated high objective response rates, durable efficacy, and acceptable safety profiles in patients (pts) with relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after failure of autologous hematopoietic cell transplantation (auto-HCT) regardless of prior brentuximab vedotin (BV) treatment (Younes A et al. Lancet Oncol 2016; Fanale M et al. ICML 2017 [Oral 125]). Recently proposed new response criteria aim to account for atypical patterns of response with checkpoint inhibitors which may not be fully captured by conventional response criteria (Cheson BD et al. Blood 2016; Younes A et al, Ann Oncol 2017). Studies in solid tumors have shown that pts may continue to derive clinical benefits from nivo beyond disease progression as defined by conventional criteria (George S et al, JAMA Oncol 2016; Long GV et al, JAMA Oncol 2017). Here we report outcomes among pts with R/R cHL treated beyond progression (TBP) in CheckMate 205. Methods: This single-arm, multicenter study enrolled pts (age ≥18 y) with R/R cHL after failure of auto-HCT into 3 independent cohorts (A: BV naïve, B: BV after auto-HCT, C: BV before and/or after auto-HCT). Nivo 3 mg/kg IV every 2 wk was given until disease progression or unacceptable toxicity. Response was assessed by 2007 International Working Group criteria. Best overall response (BOR) was assessed per investigator. A protocol amendment in July 2014 allowed pts to be TBP (investigator-assessed) if they met prespecified criteria, including deriving clinical benefit, stable performance status, and non-rapid progression. Pts TBP were required to discontinue in the event of further progression (≥10% increase in tumor burden). Tumor burden after initial progression was assessed in a prespecified analysis. Exploratory analyses assessed overall survival (OS) and time to next therapy (TTNT) in pts TBP. Results: In total, 70/243 (29%) pts were TBP: 19 in Cohort A, 23 in B, and 28 in C. Demographics were similar to the overall study population: 57% had stage IV disease at study entry, median (range) age was 37 (18-72) y, and median number of prior therapies was 3 (2-5). BOR prior to progression was complete remission (CR) in 5 (7%) pts, partial remission (PR) in 31 (44%), stable disease (SD) in 20 (29%), and progressive disease in 13 (19%) (BOR was non-evaluable in 1 pt). Among pts TBP, the initial cause of progression was a ≥50% increase in total tumor burden in 13 (19%) pts, non-target lesion progression in 17 (24%), and new lesions in 47 (67%) (pts could have multiple findings as reasons for progression). The median time to initial progression in pts TBP was 6 mo; 11 mo in pts with initial BOR of CR and 7 mo in pts with initial PR or SD. At December 2016 database lock, median (range) doses of nivo beyond progression were 8 (1-43), and median duration of treatment beyond progression was 5 (0-19) mo. Overall, 21 (30%) pts TBP remained on treatment; the most common reason for discontinuation was further disease progression (80%). The majority of pts TBP demonstrated stable reductions in tumor burden with continued treatment. Median (95% CI) TTNT from first study dose of nivo was 17 (14, not estimable) mo (Figure). Median OS from date of initial progression was not reached in pts TBP and OS was 84% (95% CI 70, 92) at 1 y. Treatment-related adverse events (TRAEs) occurred in 46% of pts (13% grade [G] 3-4) after progression, vs 64% (9% G3-4) prior to progression. Serious TRAEs after progression were aspartate aminotransferase increase (n=1) and hypercalcemia (n=1), both G3-4. Ten deaths occurred in pts TBP; 7 were due to disease progression and none were considered related to study drug. Conclusions: In total, 29% of pts from CheckMate 205 Cohort A/B/C were TBP. New lesions were the most common reason for initial progression in pts TBP. Stable reductions in tumor burden were seen with continued treatment in pts TBP, and median TTNT and OS remained high. Proposed updates to response criteria may help to better assess the long-term efficacy of checkpoint inhibitors. These data suggest that pts considered to show stable performance status, non-rapid progression, and clinical benefits despite progression according to conventional response criteria may derive long-term benefits from continued nivo treatment. Study funding: BMS. Writing support: Simon Wigfield, Caudex, funded by BMS. Disclosures Cohen: Bioinvent: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takada: Research Funding; Bristol Myers Squibb: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; LAM Therapeutics, Inc: Research Funding. Engert: Amgen: Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Affimed: Consultancy, Honoraria, Research Funding. Ansell: Merck: Research Funding; Celldex: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding. Younes: Roche: Consultancy, Honoraria, Other: Third-party medical writing assistance, under the direction of Anas Younes, was provided by Scott Malkin of Gardiner-Caldwell Communications, and was funded by F. Hoffmann-La Roche Ltd.; Bayer: Honoraria; Bristol-Myers Squibb: Honoraria; Novartis: Research Funding; Janssen: Honoraria; Merck: Honoraria; Curis: Research Funding; Sanofi: Honoraria; Takeda Millenium: Honoraria; Johnson & Johnson: Research Funding; Seattle Genetics: Honoraria; Incyte: Honoraria; Celgene: Honoraria. Trneny: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Savage: Roche: Research Funding; Seattle Genetics: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Merck: Honoraria; Celgene: Consultancy. Ramchandren: Seattle Genetics: Consultancy; Janssen: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding. Collins: ADC Therapeutics: Research Funding; Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; Celgene: Research Funding; Celleron: Consultancy; MSD: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Research Funding; Amgen: Research Funding. Fanale: AMGEN: Membership on an entity's Board of Directors or advisory committees; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TAKEDA: Honoraria, Research Funding; ONYX: Research Funding; SEATTLE GENETICS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MOLECULAR TEMPLATES: Research Funding; MERCK: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GENENTECH: Research Funding; ADC THERAPEUTICS: Research Funding. Armand: Bristol-Myers Squibb: Consultancy, Other: research funding (institutional); Merck: Consultancy, Other: research funding (institutional); Infinity: Consultancy; Pfizer: Consultancy, Other: research funding (institutional); Affimed: Other: research funding (institutional); Otsuka: Other: research funding (institutional); Sequenta: Other: research funding (institutional); Sigma Tau: Other: research funding (institutional); Roche: Other: research funding (institutional); Tensha: Other: research funding (institutional). Zinzani: Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. De Boer: Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees, Other: Non-restricted grant for research in head and neck cancer; Eisai: Membership on an entity's Board of Directors or advisory committees; Astellas: Other: member of Independent Data Monitoring Committee. Shipp: Cell Signaling: Honoraria; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Takeda: Other: Scientific Advisory Board; Merck: Other: Scientific Advisory Board; Gilead: Other: Scientific Advisory Board; AstraZeneca: Honoraria. Santoro: Merck: 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. Timmerman: Seattle Genetics: Consultancy; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Genmab: Consultancy, Equity Ownership; Kite Pharma: Research Funding; ImmuneGene: Research Funding. Sacchi: Bristol-Myers Squibb: Employment. Sy: Bristol-Myers Squibb: Employment. Kuruvilla: BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria; Janssen: Consultancy; Hoffman LaRoche: Consultancy; Seattle Genetics: Consultancy, Honoraria; Amgen: Honoraria; Roche: Honoraria; Janssen: Honoraria; Lundbeck: Honoraria; Merck: Honoraria; Karyopharm: Research Funding; Roche: Research Funding; Celgene: Honoraria, Research Funding.

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.