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LYMPHOMA

Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma

Leukemia volume 37, pages 154–163 (2023)Cite this article

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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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Fig. 1: Outcomes following CD19-CAR-T in LBCL.
Fig. 2: Characteristics at time of CAR-T treatment failure.
Fig. 3: Outcomes among patients receiving first treatment after CD19-CAR-T.

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Data availability

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.

Author information

Author notes

  1. Ana Alarcon Tomas

    Present address: Department of Hematology, Hospital Universitario Gregorio Marañón, Madrid, Spain

  2. Theodora Anagnostou

    Present address: Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, and 2. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

  3. Anna Alperovich

    Present address: BMT and Cellular Therapy Department, Monter Cancer Center, Northshore University Hospital, Lake Success, NY, USA

  4. Ellen Fraint

    Present address: Division of Pediatric Hematology, Oncology, and Cellular Therapy, The Children’s Hospital at Montefiore, Bronx, NY, USA

  5. Michal J. Besser

    Present address: Davidoff Center, Rabin Medical Center, Petach Tikva, Israel

  6. These authors contributed equally: Ana Alarcon Tomas, Joshua A Fein.

  7. These authors jointly supervised this work: Abraham Avigdor, Miguel-Angel Perales, Roni Shouval.

Authors and Affiliations

  1. Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Ana Alarcon Tomas, Warren B. Fingrut, Theodora Anagnostou, Anna Alperovich, Nishi Shah, Ellen Fraint, Richard J. Lin, Michael Scordo, Parastoo B. Dahi, Sergio Giralt, Craig Sauter, Gunjan L. Shah, Miguel-Angel Perales & Roni Shouval

  2. Ph.D. Program in Signals Integration and Modulation in Biomedicine, Cell Therapy, and Translational Medicine, University of Murcia, Murcia, Spain

    Ana Alarcon Tomas

  3. University of Connecticut Medical Center, Farmington, CT, USA

    Joshua A. Fein

  4. Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Shalev Fried, Ivetta Danylesko, Elad Jacoby, Meirav Kedmi, Arnon Nagler, Noga Shem-Tov, Avichai Shimoni, Ronit Yerushalmi, Abraham Avigdor & Roni Shouval

  5. Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel

    Shalev Fried, Michal J. Besser, Ivetta Danylesko, Elad Jacoby, Meirav Kedmi, Arnon Nagler, Noga Shem-Tov, Avichai Shimoni, Ronit Yerushalmi & Abraham Avigdor

  6. Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jessica R. Flynn & Sean M. Devlin

  7. Weill Cornell Medical College, New York, NY, USA

    Richard J. Lin, Michael Scordo, Parastoo B. Dahi, Sergio Giralt, M. Lia Palomba, Gilles A. Salles, Craig Sauter, Joachim Yahalom, Gunjan L. Shah, Miguel-Angel Perales & Roni Shouval

  8. Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Connie Lee Batlevi, M. Lia Palomba, Gilles A. Salles & Joachim Yahalom

  9. Ella Lemelbaum Institute for Immuno Oncology, Sheba Medical Center, Tel Hashomer, Israel

    Michal J. Besser

  10. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Brandon S. Imber

  11. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Mikhail Roshal

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  1. Ana Alarcon Tomas
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  2. Joshua A. Fein
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Contributions

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.

Corresponding authors

Correspondence to Miguel-Angel Perales or Roni Shouval.

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Competing interests

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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