Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, adult, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Diseases, indolent lymphoma, Therapies, Lymphoid Malignancies, Study Population, Human
Methods: Eligible patients had R/R FL or MZL after ≥2 lines of therapy (including an anti-CD20 mAb plus an alkylating agent). At enrollment, patients underwent leukapheresis, followed by conditioning chemotherapy and a single axi-cel infusion (2×106 CAR T cells/kg). The primary endpoint was ORR. Time-to-event endpoints were assessed by investigators in all enrolled patients. Exploratory analyses of lymphoma-specific survival were performed, where deaths unrelated to progression, axi-cel, or conditioning chemotherapy were not considered events of interest. Univariable and multivariable analyses were conducted using random forest analysis to rank the association of pharmacologic covariates with efficacy and toxicity.
Results: A total of 159 patients were enrolled (127 FL; 31 MZL) and 152 were treated with axi-cel (124 FL; 28 MZL). As of March 31, 2022, the median follow-up in enrolled patients was 40.5 months (range, 8.3-57.4; FL: 41.7, MZL: 31.8). ORR and CR rates were largely similar to the 2-year analysis. In all enrolled patients, median duration of response (DOR) was 38.6 months (FL: 38.6, MZL: not reached [NR]). Median DOR was NR in patients with a CR and was 4.9 months in those with a partial response. Median progression-free survival (PFS) was 40.2 months (FL: 40.2, MZL: NR). Median PFS among patients with FL with (n=70) or without (n=41) progression <2 years after initial chemoimmunotherapy (POD24) was 40.2 months and NR, respectively. Estimated 36-month PFS was largely consistent in all patients with iNHL, regardless of other high-risk characteristics, including ≥3 prior lines of therapy and double-refractory disease. Medians of time to next treatment and overall survival (OS) were not reached; 36-month OS rate was 75%. Medians of lymphoma-specific PFS and lymphoma-specific survival were not reached; 36-month rates were 65% and 89%, respectively.
Grade ≥3 adverse events (AEs) of interest occurring among treated patients since the 2-year analysis were largely in recently enrolled patients with MZL, including neurologic events in 1, cytopenias in 4, and infections in 2 (1 in FL). Since the 2-year analysis, 10 additional patients died due to progression (n=1), AEs (n=3; none related to axi-cel), and other causes (n=6).
Among treated patients, peak CAR T-cell levels were higher in those with ongoing responses at 36 months (53.9 cells/µL) than those who relapsed (29.6 cells/µL) or nonresponders (22.2 cells/µL). In patients with FL, peak levels of circulating CAR T cells normalized to baseline tumor burden in conjunction with elevated preinfusion inflammatory markers and regulatory T-cell (Treg)-related chemokines associated with relapse. Multivariable analyses in patients with FL, to be detailed in the presentation, further identified key covariates that differentially associated with efficacy and toxicity.
Conclusions: After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses in patients with R/R iNHL, with improved survival observed in patients with MZL. Late progression or death due to lymphoma or study treatment were uncommon and no new safety signals arose since the 2-year analysis. Preinfusion immunosuppressive Treg-related biomarkers associated with relapse in patients with FL.
Disclosures: Neelapu: Karus Therapeutics: Research Funding; Cellectis: Research Funding; Precision Biosciences: Consultancy, Honoraria, Other: Personal fees, Research Funding; Allogene Therapeutics: Consultancy, Honoraria, Other: Personal fees, Research Funding; Pfizer: Consultancy, Honoraria, Other: Personal fees; Medscape: Consultancy, Honoraria; Bio Ascend: Consultancy, Honoraria; Poseida: Research Funding; Calibr: Consultancy, Honoraria, Other: Personal fees; Unum Therapeutics: Consultancy, Honoraria, Other: Personal fees, Research Funding; Adicet Bio: Consultancy, Honoraria, Other: Personal fees, Research Funding; Legend Biotech: Consultancy, Honoraria, Other: Personal fees; Novartis: Consultancy, Honoraria, Other: Personal fees; Celgene: Consultancy, Honoraria, Other: Personal fees, Research Funding; Kite: Consultancy, Honoraria, Other: Personal fees, Research Funding; Merck: Consultancy, Honoraria, Other: Personal fees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Other: Personal fees, Research Funding; Incyte: Consultancy, Honoraria, Other: Personal fees; Bluebird Bio: Consultancy, Honoraria; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties: related to cell therapy.; Cell Medica/Kuur: Consultancy, Honoraria, Other: Personal fees; Aptitude Health: Consultancy, Research Funding. Chavez: Astrazeneca: Research Funding; Epyzime: Honoraria; Janssen: Research Funding; Merck: Research Funding; BeiGene: Honoraria; TG Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; ADC Therapeutics: Research Funding; AdiCet: Consultancy; GenMab: Consultancy. Sehgal: Kite, a Gilead Compnay: Other: Grants, Research Funding; OncLive: Honoraria; PeerView: Honoraria; Milltenyiz: Research Funding; Juno: Other: Grants, Research Funding. Epperla: Pharmacyclics: Other: Ad Board; Seattle Genetics: Other: Ad Board; BeiGene: Other: Ad Board; TG Therapeutics: Other: Ad Board; Novartis: Honoraria; Incyte: Speakers Bureau. Ulrickson: Stemline: Consultancy, Ended employment in the past 24 months, Honoraria; Gilead: Consultancy, Ended employment in the past 24 months, Honoraria. Bachy: Kite, a Gilead Company: Honoraria. Munshi: Kite, a Gilead Company: Speakers Bureau; Incyte: Speakers Bureau; Amgen: Current holder of stock options in a privately-held company. Casulo: Verastem: Research Funding; Secura Bio: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Bristol Myers Squibb: Research Funding. Maloney: A2 Biotherapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Data Safety Monitory Board , Research Funding; Genentech: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Legand Biotech: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Mustang Bio: Consultancy, Honoraria; Navan Technologies: Consultancy, Current holder of stock options in a privately-held company, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Umoja: Consultancy, Honoraria; Bioline Rx: Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitory Board ; Fred Hutch: Patents & Royalties: For Patients licensed to Juno ; A2 Biotherapeutics: Current holder of stock options in a privately-held company. de Vos: BeiGene: Other: Participation on a Data Safety Advisory Board. Reshef: Jasper: Consultancy; Novartis: Honoraria; Atara Biotherapeutics: Consultancy, Research Funding; Gilead: Consultancy, Honoraria, Other: Travel Support, Research Funding; Regeneron: Consultancy; Immatics: Research Funding; Bayer: Consultancy; Synthekine: Consultancy; Takeda: Research Funding; University Of Pennsylvania: Other: Data Safety Monitoring Board; Incyte: Research Funding; Shire: Research Funding; J&J: Research Funding; BMS: Honoraria; Capstan Therapeutics: Consultancy; Precision Biosciences: Research Funding; MidaTech: Consultancy; Pharmacyclics: Research Funding; TScan: Consultancy. Leslie: Eli Lily: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Jansssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celegene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Oluwole: ADC Therapeutics: Consultancy; Curio Science: Consultancy; TG Therapeutics: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Research Funding; Nektar: Consultancy; Syncopation: Consultancy; Epizyme: Consultancy. Yakoub-Agha: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Janssen: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support. Rosenblatt: University of Miami Miller School of Medicine: Patents & Royalties; Biograph 55: Research Funding; Synergys: Other. Yan: Kite, a Gilead Company: Current Employment. Song: Gilead Sciences: Current holder of stock options in a privately-held company, Patents & Royalties; Kite, a Gilead Company: Current Employment, Patents & Royalties: Gilead. Peng: Kite, a Gilead Company: Current Employment. Lui: Kite, a Gilead Company: Current Employment, Current holder of stock options in a privately-held company, Other: Travel support. Wulff: Kite, a Gilead Company: Current Employment. Shen: Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties; Atara: Patents & Royalties. Poddar: UCLA: Other: intellectual Property, Patents & Royalties; Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company. Miao: Gilead Sciences: Current holder of stock options in a privately-held company; Kite, a Gilead Company: Current Employment. Beygi: Kite, a Gilead Company: Current Employment, Research Funding. Jacobson: Ispen: Consultancy, Honoraria; ImmPACT Bio: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Other: Travel Support; Axis: Speakers Bureau; Pfizer: Other: Travel Support, Research Funding; Lonza: Consultancy, Honoraria, Other: Travel Support; Instil Bio: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Humanigen: Consultancy, Honoraria, Other: Travel Support; Epizyme: Consultancy, Honoraria; Nkarta: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; Clinical Care Options: Speakers Bureau; Precision BioSciences: Consultancy, Honoraria, Other: Travel Support; Novartis: Consultancy, Honoraria, Other: Travel Support; BMS/Celgene: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding.