Abstract
Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57–69]). Of 52 post-CAR-T biopsies evaluated by flow cytometry, 49 (94%) expressed CD19. Subsequent anti-cancer treatment was administered in 135/182 (74%) patients with CAR-T treatment failure. Median OS from the first post-CAR-T treatment was 8 months (95%CI 5.6–11.0). Polatuzumab-, standard chemotherapy-, and lenalidomide-based treatments were the most common approaches after CAR-T. No complete responses (CRs) were observed with conventional chemotherapy, while CR rates exceeding 30% were seen following polatuzumab- or lenalidomide-based therapies. Factors associated with poor OS among patients treated post-CAR-T were pre-CAR-T bulky disease (HR 2.27 [1.10–4.72]), lack of response to CAR-T (2.33 [1.02–5.29]), age >65 years (HR 2.65 [1.49–4.73]) and elevated LDH at post-CAR-T treatment (HR 2.95 [1.61–5.38]). The presence of ≥2 of these factors was associated with inferior OS compared to ≤1 (56% vs. 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise.
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The datasets generated during and/or analyzed during the current study are not publicly available due to protect study participant privacy but are available from the corresponding author upon reasonable request and approval by MSK IRB
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Acknowledgements
This research was supported in part by the Memorial Sloan Kettering Cancer Center Core grant (P30 CA008748) from the National Institutes of Health/National Cancer Institute. RS was supported by the American Society of Transplantation and Cellular Therapy New Investigator Award, the American Society of Hematology Fellow Scholar Award, a grant from the Long Island Sound Chapter, Swim Across America, the Robert Hirschhorn Award, and the Memorial Sloan Kettering Steven Greenberg Lymphoma Research Award. AAT was supported by a grant from the Alfonso Martín Escudero. JAF was supported by an HONORS Award from the American Society of Hematology.
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Conception and design: RS, AAT, JAF, M-AP. Provision of study materials or patients: RJL, MS, CB, MB, PBD, ID, SG, BSI, EJ, MK, AN, LP, GS, CS, NS-T, AS, MR, JY, RY, GS, AA, M-AP. Collection and assembly of data: AAT, JAF, SF, WBF, TA, AA, NS, EF, RJL, MS, MR, RS. Data analysis and interpretation: JF, SD, RS, AAT, JAF, M-AP. Manuscript writing: All authors. Final approval of manuscript: All authors. Accountable for all aspects of the work: All authors.
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RS: Medexus, Consultancy; PBD: Kite/Gilead, Advisory board; SAG: Actinnum, Membership on an entity’s Board of Directors or advisory committees; CELGENE, Membership on an entity’s Board of Directors or advisory committees; BMS., Membership on an entity’s Board of Directors or advisory committees; SANOFI, Membership on an entity’s Board of Directors or advisory committees; AMGEN, Membership on an entity’s Board of Directors or advisory committees; PFIZER, Membership on an entity’s Board of Directors or advisory committees; JENSENN, Membership on an entity’s Board of Directors or advisory committees; GSK., Membership on an entity’s Board of Directors or advisory committees; JAZZ, Membership on an entity’s Board of Directors or advisory committees; GAS: AbbVie Inc, Allogene Therapeutics, Autolus Therapeutics, BeiGene Ltd, Bristol-Myers Squibb Company, Celgene Corporation, Debiopharm Group, Genmab, Kite, A Gilead Company, Incyte Corporation, Janssen Biotech Inc, Miltenyi Biotec, MorphoSys, Novartis, Roche, Advisory Committee; Bristol-Myers Squibb Company, Celgene Corporation, Debiopharm Group, Genmab, Kite, A Gilead Company, Incyte Corporation, Miltenyi Biotec, MorphoSys, Novartis, Roche Laboratories Inc, Consultancy; CSS: Juno Therapeutics, Consultancy and Research Funding; Sanofi-Genzyme, Consultancy and Research Funding; Spectrum Pharmaceuticals, Consultancy; Novartis, Consultancy; Genmab, Consultancy; Precision Biosciences, Consultancy; Kite/Gilead, Consultancy; Celgene, Consultancy and Research Funding; Gamida Cell, Consultancy; GSK., Consultancy; Bristol-Myers Squibb, Research Funding; MS: McKinsey & Company, Consultancy; Angiocrine Bioscience, Consultancy and Research Funding; Omeros Corporation, Consultancy and research funding; Amgen, Inc., Research funding; Kite - A Gilead Company, Advisory Board; i3 Health, Other: Honorarium, CME activity; Medscape, LLC, Other: Honorarium, CME activity; GS: Amgen, Research Funding; Janssen Pharmaceutica, Research Funding; AA: Takeda, Consultancy and honoraria; Janseen, Research Funding; BMS, Research Funding; Gilead, Consultancy and honoraria; Pfizer, Consultancy and honoraria; M-AP: Bristol-Myers Squibb, Honoraria; Celgene, Honoraria; Equilium, Honoraria; Incyte, Honoraria and Other: Clinical trial support to institution; Karyopharm, Honoraria; Kite/Gilead, Honoraria and Other: Clinical trial support to institution; Merck, Honoraria; Miltenyi Biotec, Honoraria and Other; MorphoSys, Honoraria; Novartis, Honoraria and Other: Clinical trial support to institution; Nektar Therapeutics, Honoraria and Other; Omeros, Honoraria; Takeda, Honoraria; Cidara Therapeutics, Honoraria; Medigene, Honoraria; Sellas Life Sciences, Honoraria; Servier, Honoraria; NexImmune, Honoraria; EJ: Novartis, Advisory board, Honoraria; JY: Convergent R.N.R Ltd., Advisory board; MR: Celgene, Provision of Services; Auron Therapeutics, Inc., Ownership/Equity Interests; Provision of Services; Physicians’ Education Resourc, Provision of Services. M.J.B. Envizion Medical, Membership on an entity’s Board of Directors or advisory committees; Biological Industries (a Sartorius Company), Gilboa Therapeutics, Consultancy; Envizion Medical, Other: Patents.
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Alarcon Tomas, A., Fein, J.A., Fried, S. et al. Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma. Leukemia 37, 154–163 (2023). https://doi.org/10.1038/s41375-022-01739-2
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DOI: https://doi.org/10.1038/s41375-022-01739-2
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