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4660 3-Year Follow-up Analysis of ZUMA-5: A Phase 2 Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory (R/R) Indolent Non-Hodgkin Lymphoma (iNHL)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
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
Monday, December 12, 2022, 6:00 PM-8:00 PM

Sattva S. Neelapu, MD1, Julio Chavez2, Alison R. Sehgal, MD3, Narendranath Epperla, MD, MS4,5, Matthew Ulrickson, MD6, Emanuel Bachy, MD, PhD7*, Pashna N. Munshi, MD8*, Carla Casulo, MD9, David G. Maloney, MD, PhD10, Sven de Vos, MD, PhD11, Ran Reshef, MD, MSc12, Lori A. Leslie, MD13*, Olalekan O. Oluwole, MBBS14, Ibrahim Yakoub-Agha, MD, PhD15, Rashmi Khanal, MD16*, Joseph D. Rosenblatt, MD17, Jiali Yan, MS18*, Qinghua Song, PhD18*, Weixin Peng, MS18*, Christine Lui, MS18*, Jacob Wulff, DrPH19*, Rhine R. Shen, PhD18*, Soumya Poddar, PhD18*, Harry Miao, MD, PhD18*, Sara Beygi, MD18* and Caron A. Jacobson, MD20

1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
2University of South Florida H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
3UPMC Hillman Cancer Center, Pittsburgh, PA
4The Ohio State University Comprehensive Cancer Center, Columbus, OH
5The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH
6Banner MD Anderson Cancer Center, Gilbert, AZ
7Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
8Georgetown Lombardi Comprehensive Cancer Center, Washington, DC
9University of Rochester Medical Center - James P. Wilmot Cancer Center, Rochester, NY
10Fred Hutchinson Cancer Research Center, Seattle, WA
11Ronald Reagan University of California Los Angeles Medical Center, Los Angeles, CA
12Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY
13John Theurer Cancer Center, Hackensack, NJ
14Vanderbilt University Medical Center, Nashville, TN
15CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000 Lille, France
16Fox Chase Cancer Center, Philadelphia, PA
17University of Miami Sylvester Comprehensive Cancer Center, Miami, FL
18Kite, a Gilead Company, Santa Monica, CA
19Kite, A Gilead Company, Santa Monica
20Dana-Farber Cancer Institute, Boston, MA

Introduction: Axi-cel, an autologous anti-CD19 CAR T-cell therapy, is approved for the treatment of adults with follicular lymphoma (FL) after ≥2 lines of prior therapy. ZUMA-5 is a Phase 2, multicenter, single-arm study of axi-cel in patients with R/R iNHL (FL and marginal zone lymphoma [MZL]). In the 2-year analysis of ZUMA-5, the overall response rates (ORR) in patients with FL and MZL were 94% (79% complete response [CR] rate) and 83% (63% CR rate), respectively (Neelapu et al. ASH 2021. Abstract 93). Here, we report updated clinical and pharmacologic outcomes from ZUMA-5 after >3 years median follow-up.

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.

*signifies non-member of ASH