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Multicenter Study
. 2024 Jun 27;143(26):2722-2734.
doi: 10.1182/blood.2023023447.

Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity

Frederick L Locke  1 , Tanya Siddiqi  2 , Caron A Jacobson  3 , Armin Ghobadi  4 , Sairah Ahmed  5 , David B Miklos  6 , Miguel-Angel Perales  7 , Javier Munoz  8 , Warren B Fingrut  7 , Martina Pennisi  9 , Jordan Gauthier  10 , Mazyar Shadman  10 , Lohith Gowda  11 , Abu-Sayeef Mirza  1   11 , Muhammad Bilal Abid  12 , Sanghee Hong  13 , Navneet S Majhail  14 , Mohamed A Kharfan-Dabaja  15 , Arushi Khurana  16 , Talha Badar  15 , Yi Lin  16 , N Nora Bennani  16 , Megan M Herr  17 , Zhen-Huan Hu  18 , Hai-Lin Wang  18 , Anjani Baer  18 , Elande Baro  18 , Harry Miao  18 , Clare Spooner  18 , Hairong Xu  18 , Marcelo C Pasquini  12
Affiliations
Multicenter Study

Real-world and clinical trial outcomes in large B-cell lymphoma with axicabtagene ciloleucel across race and ethnicity

Frederick L Locke 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) large B-cell lymphoma (LBCL). Despite extensive data supporting its use, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients who received axi-cel between 2017 and 2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 trials, respectively. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37; 95% CI, 0.22-0.63) and lower complete response rate (OR, 0.57; 95% CI, 0.33-0.97) than NH White patients. NH Black patients also had a shorter progression-free survival vs NH White (HR, 1.41; 95% CI, 1.04-1.90) and NH Asian patients (HR, 1.67; 95% CI, 1.08-2.59). NH Asian patients had a longer duration of response than NH White (HR, 0.56; 95% CI, 0.33-0.94) and Hispanic patients (HR, 0.54; 95% CI, 0.30-0.97). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade immune effector cell-associated neurotoxicity syndrome were observed in NH White patients than in other patients. These results provide important context when treating patients with R/R LBCL with CAR T-cell therapy across different racial and ethnic groups. ZUMA-1 and ZUMA-7 (ClinicalTrials.gov identifiers: #NCT02348216 and #NCT03391466, respectively) are registered on ClinicalTrials.gov.

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Conflict of interest statement

Conflict-of-interest disclosure: F.L.L. reports a scientific advisory role/consulting role with A2, Allogene, Amgen, bluebird bio, Bristol Myers Squibb/Celgene, Calibr, Caribou, Cellular Biomedicine Group, Cowen, Daiichi Sankyo, EcoR1, Emerging Therapy Solutions, GammaDelta Therapeutics, Gerson Lehrman Group, Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Takeda, Wugen, and Umoja; reports patents, royalties, and other intellectual property in several patents held by the institution in his name (unlicensed) in the field of cellular immunotherapy; reports travel support from A2 Bio; and reports other relationships with Allogene (institutional), Aptitude Health, American Society of Hematology, bluebird bio (institutional), BioPharma Communications CARE Education, Bristol Myers Squibb (institutional), CERo Therapeutics (institutional), Clinical Care Options Oncology, Imedex, Kite (a Gilead company; institutional), Novartis (institutional), National Cancer Institute, Leukemia and Lymphoma Society, and Society for Immunotherapy of Cancer. T.S. held a consultancy or advisory role with AbbVie, AstraZeneca, BeiGene, Celgene, Juno, and Kite (a Gilead company), and Pharmacyclics; reports speakers' bureau participation for AstraZeneca, BeiGene, and Bristol Myers Squibb; and reports institutional research funding from Ascentage Pharma, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Juno, Kite (a Gilead company), Oncternal, Pharmacyclics, and TG Therapeutics. C.A.J. held a consulting/advisory role with AbbVie, Abintus Bio, ADC Therapeutics, Bristol Myers Squibb/Celgene, Caribou Bio, Daiichi Sankyo, ImmPACT Bio, Instil Bio, Ipsen, Kite (a Gilead company), Miltenyi Biotec, MorphoSys, Novartis, and Synthekine; and reports research funding from Kite (a Gilead company) and Pfizer. A.G. received honoraria from Kite (a Gilead company); served in a consulting/advisory role for Amgen, Atara, Bristol Myers Squibb, CRISPR Therapeutics, Kite, and Wugen Inc; and reports research funding from Amgen, Genentech, and Kite. S.A. received research funding from Bristol Myers Squibb, Merck, Nektar, Tessa Therapeutics, and Xencor. D.B.M. received honoraria and travel support from Janssen; reports a consulting/advisory role for Adaptive Biotechnologies, Bristol Myers Squibb, Janssen, Kite (a Gilead company), and Miltenyi Biotec; reports research funding from 2Seventy Bio, Adicet, Allogene, Fate Therapeutics, Kite, and Miltenyi Biotec; and reports patents, royalties, or other intellectual property from chronic graft-versus-host disease (cGVHD) patent holder for ibrutinib as cGVHD therapy but no compensation. M.-A.P. received honoraria from AbbVie, Astellas, Celgene, Bristol Myers Squibb, Incyte, Karyopharm, Kite (a Gilead company), Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, and Takeda; served in a consulting/advisory role for Merck and Omeros; reports institutional research funding for clinical trials from Incyte, Kite, Miltenyi Biotec, and Novartis; and reports other relationship with a Data Safety Monitoring Board: Cidara Therapeutics, Medigene, and Servier. J.M. received honoraria from Curio, Kyowa Kirin, OncView, Physicians' Education Resource, Targeted Oncology, and Seagen; reports consulting/advisory role for ADC Therapeutics, Alexion, Bayer, BeiGene, Bristol Myers Squibb, Debiopharm, Epizyme, Fosunkite, Genmab, Innovent, Janssen, Juno/Celgene, Karyopharm, Kite (a Gilead company), Kyowa Kirin, Lilly/Loxo, MEI Pharma, MorphoSys/Incyte, Novartis, Pfizer, Pharmacyclics/AbbVie, Seagen, Servier, TG Therapeutics, and Zodiac; reports speakers’ bureau participation for Acrotech/Aurobindo, AstraZeneca, Bayer, BeiGene, Celgene/Bristol Myers Squibb, Genentech/Roche, Kite (a Gilead company), Kyowa Kirin, Pharmacyclics/Janssen, Seagen, and Verastem; and reports research funding from Bayer, Celgene, Genentech, Incyte, Janssen, Kite, Merck, Millennium, Pharmacyclics, Portola, and Seagen. M.P. reports honoraria from Bristol Myers Squibb; served in a consulting/advisory role for Nektar Therapeutics; and declares travel support from Novartis. J.G. had a consulting/advisory role with Janssen, Kite (a Gilead company), Legend Biotech, MorphoSys, and Sobi; and received research funding from Angiocrine Bioscience, Celgene, Juno Therapeutics (a Bristol Myers Squibb company), and Sobi. M.S. had employment with Bristol Myers Squibb (spouse); served in a consulting/advisory role for AbbVie, Adaptimmune, Adaptive Biotechnologies, AstraZeneca, Atara Biotherapeutic, BeiGene, Bristol Myers Squibb, Eli Lilly, Epizyme, Fate Therapeutics, Genentech, Innate Pharma, Kite (a Gilead company), MEI Pharma, Merck, MorphoSys/Incyte, Mustang Bio, Pharmacyclics, Regeneron, Sound Biologics, and TG Therapeutics; and reports research funding from AbbVie, AstraZeneca, Atara Biotherapeutics, BeiGene, Bristol Myers Squibb, Celgene, Genentech, Genmab, Gilead, MorphoSys/Incyte, Mustang Bio, Pharmacyclics, Sunesis, and TG Therapeutics. L.G. received honorarium from Bristol Myers Squibb. M.B.A. received research funding from Ansun, BioPharma Inc, and Janssen. S.H. had employment with Adaptive Biotechnologies. N.S.M. had employment with, and stock or other ownership in, HCA Healthcare; and reports a consulting/advisory role for Anthem, Inc. M.A.K.-D. received research funding from Bristol Myers Squibb, Pharmacyclics, and Novartis. T.B. had stock or other ownership in Aprea Therapeutics; received honoraria from Pfizer Hematology-Oncology; and reports research funding from Mayo Clinic, Cancer Center Support Grant. Y.L. reports a consulting/advisory role for Kite/Gilead, Celgene/Bristol Myers Squibb, Juno/Bristol Myers Squibb, bluebird bio, Janssen, Legend Biotech, Gamida Cell, Novartis, Iovance, Takeda, Fosun Kite, and Pfizer; and received research funding from Kite/Gilead, Celgene/Bristol Myers Squibb, bluebird bio, Janssen, Legend Biotech, Merck, Takeda, and Boston Scientific. N.N.B. had a consulting/advisory role for Acrotech, Affimed, Astellas, Kymera, and Secura Bio; and received research funding from Affimed, Daiichi Sankyo, and Kite (a Gilead company). Z.-H.H. had employment with Kite (a Gilead company); and stock or other ownership in Gilead Sciences. H.-L.W. had employment with Kite (a Gilead company). A.B. had employment with, and stock or other ownership in, Gilead Sciences. E.B. had employment with, stock or other ownership in, and consulting/advisory role for, Kite (a Gilead company). H.M. had employment with Kite (a Gilead company); and stock or ownership in Gilead Sciences. C.S. had employee with Kite (a Gilead company); and stock or other ownership in Gilead Sciences. H.X. had employment with Kite (a Gilead company). M.C.P. received honoraria from Celgene; reports consulting/advisory role for Amgen, Medigene, and Pfizer; and reports research funding from Bristol Myers Squibb, Kite (a Gilead company), and Novartis. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient geographic distribution in the real world and clinical trials. The race and ethnicity distributions of patients enrolled in the real-world (red circles) and clinical trial (green circles) settings within authorized treatment centers at the city level are shown. The size of the circle is commensurate with the number of patients enrolled in that setting. RWE, real-world evidence.
Figure 2.
Figure 2.
Response by race and ethnicity in the real world and clinical trials. ORR and CR rates among patients in (A) the real world, (B) ZUMA-1, and (C) ZUMA-7. Per central assessment.
Figure 3.
Figure 3.
Duration of response and survival outcomes by race and ethnicity in the real world. (A) DOR, (B) PFS, and (C) OS. PR, partial response.
Figure 4.
Figure 4.
Outcomes from the real world with multivariable adjustment. (A) Adjusted ORs for ORR, and CR rate; and HRs for DOR, PFS, and OS; and (B) adjusted OR for CRS, ICANS, prolonged neutropenia, and prolonged thrombocytopenia. aAdditional covariates associated with efficacy outcomes were adjusted (data not shown). bOR was used for the analysis of ORR and CR, and HR was used for the analysis of DOR, PFS, and OS. cVariables with multivariate P < .05. NHA, non-Hispanic Asian; NHB, non-Hispanic Black; NHW, non-Hispanic White.
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