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Multicenter Study
. 2024 Feb 8;143(6):496-506.
doi: 10.1182/blood.2023021243.

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Sattva S Neelapu  1 , Julio C Chavez  2 , Alison R Sehgal  3 , Narendranath Epperla  4 , Matthew Ulrickson  5 , Emmanuel Bachy  6 , Pashna N Munshi  7 , Carla Casulo  8 , David G Maloney  9 , Sven de Vos  10 , Ran Reshef  11 , Lori A Leslie  12 , Olalekan O Oluwole  13 , Ibrahim Yakoub-Agha  14 , Rashmi Khanal  15 , Joseph Rosenblatt  16 , Ronald Korn  17 , Weixin Peng  18 , Christine Lui  18 , Jacob Wulff  18 , Rhine Shen  18 , Soumya Poddar  18 , A Scott Jung  18 , Harry Miao  18 , Sara Beygi  18 , Caron A Jacobson  19
Affiliations
Multicenter Study

Three-year follow-up analysis of axicabtagene ciloleucel in relapsed/refractory indolent non-Hodgkin lymphoma (ZUMA-5)

Sattva S Neelapu et al. Blood. .

Abstract

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel for patients with R/R indolent non-Hodgkin lymphoma (iNHL; N = 104), including FL and marginal zone lymphoma (MZL). In the primary analysis (median follow-up, 17.5 months), the overall response rate (ORR) was 92% (complete response rate, 74%). Here, we report long-term outcomes from ZUMA-5. Eligible patients with R/R iNHL after ≥2 lines of therapy underwent leukapheresis, followed by lymphodepleting chemotherapy and axi-cel infusion (2 × 106 CAR T cells per kg). The primary end point was ORR, assessed in this analysis by investigators in all enrolled patients (intent-to-treat). After median follow-up of 41.7 months in FL (n = 127) and 31.8 months in MZL (n = 31), ORR was comparable with that of the primary analysis (FL, 94%; MZL, 77%). Median progression-free survival was 40.2 months in FL and not reached in MZL. Medians of overall survival were not reached in either disease type. Grade ≥3 adverse events of interest that occurred after the prior analyses were largely in recently treated patients. Clinical and pharmacokinetic outcomes correlated negatively with recent exposure to bendamustine and high metabolic tumor volume. After 3 years of follow-up in ZUMA-5, axi-cel demonstrated continued durable responses, with very few relapses beyond 2 years, and manageable safety in patients with R/R iNHL. The ZUMA-5 study was registered at www.clinicaltrials.gov as #NCT03105336.

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Conflict of interest statement

Conflict-of-interest disclosure: S.S.N. reports a consulting/advisory role for Kite/Gilead, Merck, Sellas Life Sciences, Athenex, Allogene, Incyte, Adicet Bio, Bristol Myers Squibb, Bluebird Bio, Fosun Kite, Sana Biotechnology, Caribou, Astellas Pharma, MorphoSys, Janssen, Chimagen, ImmunoACT, Orna Therapeutics, Takeda, and Synthekin; research funding from Kite, Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet Bio, and Sana Biotechnology; stock options from Longbow Immunotherapy; and patents, royalties, or other intellectual property related to cell therapy. J.C.C. reports a consulting/advisory role for ADC Therapeutics, AdiCet, AstraZeneca, Bristol Myers Squibb, Genentech, Genmab, Kite, and Novartis; speakers’ bureau participation for BeiGene and Lilly; and research funding from ADC Therapeutics, AstraZeneca, Janssen, and Merck. A.R.S. reports grants, contracts, or research funding from Juno and Kite. N.E. reports a consulting/advisory role and honoraria with ADC Therapeutics, Lilly, Merck, and Novartis; speakers’ bureau participation for Incyte and BeiGene; and research funding from BeiGene. M.U. reports consulting/advisory role for Gilead Sciences and Stemline. E.B. reports honoraria from Kite. P.N.M. reports a consulting/advisory role for Incyte and speakers' bureau participation for Incyte and Kite. C.C. reports research funding from Bristol Myers Squibb, Genentech, Gilead Sciences, and Verastem. D.G.M. reports consulting or honoraria fees from A2 Biotherapeutics, Amgen, Bristol Myers Squibb, Celgene, Genentech, Gilead Sciences, Incyte, Janssen, Juno Therapeutics, Kite, Legend Biotech, MorphoSys, Mustang Bio, Navan Technologies, Novartis, Pharmacyclics, and Umoja; participation on a data safety monitory board or advisory board for Bioline Rx and Celgene; research funding paid directly to institution from Celgene, Juno, and Kite; rights to royalties from Fred Hutch for patents licensed to Juno; and stock options from A2 Biotherapeutics and Navan Technologies. S.d.V. reports participation on a data safety advisory board for BeiGene. R.R. reports honoraria from Gilead and Bristol Myers Squibb; consulting/advisory role for Atara Biotherapeutics, Gilead Sciences, Takeda, Incyte, Instil Bio, Regeneron, TScan, Synthekine, Orca, MidaTech, Capstan and Jasper; research funding (to the institution) from Atara Biotherapeutics, Incyte, Sanofi, Immatics, TCR2 Therapeutics, Takeda, Gilead Sciences, CareDx, TScan, Synthekine, Bristol Myers Squibb, Johnson & Johnson and Precision Biosciences; expert testimony to Bayer; and travel support from Gilead. L.A.L. reports a consulting/advisory role for AbbVie, AstraZeneca, BeiGene, Eli Lilly, Epizyme, Janssen/Johnson & Johnson, Kite, Merck, Pharmacyclics, Seagen, and TG Therapeutics; speakers’ bureau participation for and travel support from AbbVie, AstraZeneca, BeiGene, Celgene/Bristol Myers Squibb, Eli Lilly, Epizyme, Kite, Janssen/Pcyc, Pharmacyclics, Seagen, and TG Therapeutics. O.O.O. reports honoraria from Gilead and Pfizer; a consultancy/advisory role for AbbVie, ADC, Curio Science, Epizyme, Gilead, Janssen, Kite, Pfizer, Nektar, Novartis, Syncopation, and TGR BioSciences; other research funding to institution from Allogene, Daichi Sankyo, Kite, and Pfizer. I.Y.-A. reports honoraria from Bristol Myers Squibb, Janssen, Kite, a Gilead Company, and Novartis; consulting/advisory role for Kite and Novartis; and travel support from Kite. J.R. reports research funding from Biograph 55; patents, royalties, or intellectual property from University of Miami Miller School of Medicine; and other relationships with Synergys. R. Korn reports employment with Imaging Endpoints; leadership at Imaging Endpoints; and stock or other ownership in Globavir, Renibus, and Verve. W.P. and J.W. report employment with Kite. C.L. reports employment with, stock or other ownership in, and travel support from Kite. R.S. reports employment with and stock or other ownership in Kite; and patents, royalties and other intellectual property from Atara and Kite. S.P. reports employment with and travel support from Kite; and patents, royalties, or other intellectual property from University of California Los Angeles. A.S.J. reports employment with Kite; and stock or other ownership in Amgen, Gilead Sciences, Kura, and Turning Point. H.M. reports employment with Kite; and stock or ownership in Gilead Sciences. S.B. reports employment with, stock or other ownership in, and travel support from Kite. C.A.J. reports honoraria from Kite, Novartis, Bristol Myers Squibb/Celgene, Instill Bio, ImmPACT Bio, Lonza, Ipsen, Epizyme, BlueBird Bio, and Daiichi-Sankyo; consulting/advisory role for Kite, Novartis, Bristol Myers Squibb/Celgene, Instill Bio, ImmPACT Bio, Lonza, Ipsen, Epizyme BlueBird Bio, and Daiichi-Sankyo; and research funding from Kite and Pfizer. R. Khanal declares no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
PFS, OS, and TTNT. Kaplan-Meier estimates of (A) PFS, (B) OS, and (C) TTNT by investigator assessment based on the disease type among the 159 enrolled patients with iNHL. mo, month; NE, not estimable; NR, not reached.
Figure 2.
Figure 2.
Lymphoma-specific survival outcomes of patients with FL based in cumulative incidence and competing risk. Cumulative incidence plots of competing risk lymphoma-specific (A) PFS and (B) OS by investigator assessment for enrolled patients with FL. Main events included those due to lymphoma or study treatment complications. Events due to reasons other than lymphoma or study treatment complications were considered competing risks.
Figure 3.
Figure 3.
PFS of patients with FL based on the time point of bendamustine use before axi-cel infusion. Kaplan-Meier estimates of PFS among enrolled patients with FL by investigator assessment in those who had no prior bendamustine exposure, received bendamustine within 6 months of leukapheresis, received bendamustine between 6 and 12 months of leukapheresis, and received bendamustine >12 months before leukapheresis.
Figure 4.
Figure 4.
PFS of patients with FL based on the quartile of baseline metabolic tumor volume. Kaplan-Meier plot of PFS per investigator assessment based on the quartile of baseline metabolic tumor volume of evaluable enrolled patients with FL. MTV, metabolic tumor volume.
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References

    1. Freedman A, Jacobsen E. Follicular lymphoma: 2020 update on diagnosis and management. Am J Hematol. 2020;95(3):316–327. - PubMed
    1. Leslie LA. Novel therapies for follicular lymphoma and other indolent non-Hodgkin lymphomas. Curr Treat Options Oncol. 2021;22(12):111. - PMC - PubMed
    1. Batlevi CL, Sha F, Alperovich A, et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10(7):74. - PMC - PubMed
    1. Casulo C, Larson MC, Lunde JJ, et al. Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study. Lancet Haematol. 2022;9(4):e289–e300. - PMC - PubMed
    1. Casulo C, Byrtek M, Dawson KL, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare study. J Clin Oncol. 2015;33(23):2516–2522. - PMC - PubMed

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