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LYMPHOMA

Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis

Leukemia (2024)Cite this article

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Abstract

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2–9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4–52.8) and the probability of overall survival was 63.8% (95% CI 54.4–72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5–15.4) and 47.3% (95% CI 38.2–56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS.

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Fig. 1: Univariable analysis outcomes.
Fig. 2: Forest plot of univariable analyses.

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Data availability

The CIBMTR makes its publication analysis datasets freely available to the public for secondary analysis while safeguarding the privacy of participants and protecting confidential and proprietary data: https://www.cibmtr.org/referencecenter/publist/pubdsdownload.

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Acknowledgements

The CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); N00014-21-1-2954 and N00014-23-1-2057 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptimmune; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Allogene; Allovir, Inc.; Amgen, Inc.; Angiocrine; Astellas Pharma US; Atara Biotherapeutics; BeiGene; bluebird bio, inc.; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; Elevance Health; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt Pharmaceuticals; Merck & Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, Inc.; Ossium Health, Inc.; Pfizer, Inc.; Pharmacyclics, LLC, An AbbVie Company; PPD Development, LP; Regimmune; Sanofi; Sarah Cannon; Sobi, Inc.; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Vertex Pharmaceuticals; Vor Biopharma Inc.; Xenikos BV. TPW is a K12 Scholar supported by the National Cancer Institute of the National Institutes of Health under Award Number K12CA226330. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Division of Transplantation and Cellular Therapy, Department of Medicine, University of Miami Miller School of Medicine, Miami, USA

    Trent P. Wang & Antonio Jimenez Jimenez

  2. BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Kwang W. Ahn & Mehdi Hamadani

  3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA

    Kwang W. Ahn & Manmeet Kaur

  4. Clinical Research Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA

    Mazyar Shadman

  5. University of Kansas Cancer Center, Division of Hematologic Malignancies and Cellular Therapeutics, Kansas City, KS, USA

    Nausheen Ahmed

  6. Department of Medical Oncology, Inselspital, Bern University Hospital, Bern, Switzerland

    Ulrike Bacher

  7. Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical Center, Worcester, MA, USA

    Jan Cerny

  8. Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

    Andy Chen

  9. Division of Hematology, Department of Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Narendranath Epperla

  10. Massachusetts General Hospital Cancer Center, Harvard Medical School, Division of Hematology & Oncology, Boston, MA, USA

    Matthew Frigault

  11. Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Natalie Grover

  12. University of Colorado Cancer Center, Aurora, CO, USA

    Bradley Haverkos

  13. Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA

    Brian Hill & Craig Sauter

  14. Cell Therapy and Transplant Program, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nasheed Hossain

  15. Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA

    Madiha Iqbal & Muhamad Alhaj Moustafa

  16. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Tania Jain

  17. Kansas City VA Medical Center, Kansas City, MO, USA

    Maxwell M. Krem

  18. Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA

    Joseph Maakaron

  19. Division of Hematology/Oncology, Karmanos Cancer Institute, Detroit, MI, USA

    Dipenkumar Modi

  20. The David and Etta Jonas Center for Cellular Therapy, University of Chicago, Chicago, IL, USA

    Peter Riedell

  21. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin Savani

  22. Department of Oncology, Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY, USA

    R. Alejandro Sica

  23. Institut Català d’Oncologia, Hospital Duran i Reynals, Barcelona, Spain

    Anna Sureda

  24. Division of Hematology and Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Kitsada Wudhikarn

  25. Department of Hematology and Hematopoietic Stem Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA

    Alex F. Herrera

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  1. Trent P. Wang
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  16. Tania Jain
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  27. Craig Sauter
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Contributions

Conception and design: Trent Wang, Antonio Jimenez Jimenez, Kwang W. Ahn and Mehdi Hamadani. Financial support: CIBMTR. Collection and assembly of data: Manmeet Kaur and Mehdi Hamadani. Data analysis: Mehdi Hamadani, Manmeet Kaur & Kwang W. Ahn. Interpretation: All authors. Manuscript writing: First draft prepared by Trent Wang and Antonio Jimenez. All authors helped revise the manuscript. Final approval of manuscript: All authors.

Corresponding author

Correspondence to Mehdi Hamadani.

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Competing interests

TPW reports consultancy for: Kite/a Gilead Company, Incyte, Sanofi. He has received research funding from: Syndax/Incyte, AlloVir, Kadmon/Sanofi. MS reports consultancy for: AbbVie, Genentech, AstraZeneca, Pharmacyclics, BeiGene, BMS, MorphoSys/Incyte, Kite, Eli Lilly, Genmab, Mustang Bio, Regeneron, ADC therapeutics, Fate Therapeutics, Janssen and MEI Pharma. He receives research funding: Mustang Bio, BMS, Pharmacyclics, Genentech, AbbVie,TG Therapeutics, BeiGene, AstraZeneca, Genmab, MorphoSys/Incyte, Vincerx. NA reports institutional research funding and consultancy fees from Kite/Gilead; and advisory board funds from Bristol Myers Squibb. JC reports consultancy for: Bristol Myers Squibb and Merit CRO. He serves as a data safety monitoring board member with ICON-Allovir and ICON-Prolacta. He owns stock in Actinium Pharmaceuticals, Bluebird Bio/2Seventy, Dynavax Technologies, aTyr Pharma, Gamida Cell Ltd, Novavax Inc, Ovid Therapeutics, Vaxart, and Veru. AC reports consultancy for: Elsevier, Kite and research funding from: Novartis, Fate Therapeutics, Kite, BMS. MJF reports consulting and advisory roles for Kite/Gilead, BMS, Novartis, JnJ/Legend. He reports research funding from Arcellx, Kite/Gilead, Novartis, Incyte. NG reports Honoraria from: Novartis, Kite, BMS, Caribou, Genentech, Janssen, Seagen, ADC Therapeutics. Brian Hill reports research funding and consultancy from Gilead, Novartis and BMS. TJ receives institutional research funding from” CTI Biopharma, Kartos therapeutics, Incyte, Bristol Myers Squibb; Advisory board participation with: Care Dx, Bristol Myers Squibb, Incyte, Abbvie, CTI, Kite, Cogent Biosciences, Blueprint Medicine, Telios pharma, Protagonist therapeutics; Education activity with Oncology APP, Binaytara Foundation, and ASH Highlights. JEM reports: research funding from Gilead, Atara, CRISPR, Precision Biosciences, and Scripps Research Institute. Dipenkumar Modi reports research funding from: Genentech, ADC Therapeutics, Karyopharm Therapeutics, Genmab. Consultancy: SeaGen, MorphoSys, ADC Therapeutics, Genmab. Honorarium: AstraZeneca, Beigene. MM reports consultancy from: AbbVie, CSL Behring. Peter Riedell reports consultancy and/or advisory board member for AbbVie, Novartis, BMS, ADC Therapeutics, Kite/Gilead, Sana Biotechnology, Nektar Therapeutics, NurixTherapeutics, Intellia Therapeutics, CVS Caremark, Genmab, BeiGene, Janssen, and Pharmacyclics. He has received honoraria from Novartis. Research support from BMS, Kite Pharma, Novartis, MorphoSys, CRISPR Therapeutics, Calibr, Xencor, Fate Therapeutics, AstraZeneca, Genentech, and Tessa Therapeutics. AS report Consultancy: Takeda, BMS/Celgene, Novartis, Janssen, Gilead, Sanofi. Research support: Takeda, BMS/Celgene.Honoraria: Takeda, BMS/Celgene, MSD, Janssen, Amgen, Novartis, Gilead Kite, Sanofi, Roche, Alexion. Speaker’s Bureau: Takeda. AH reports consultancy from: Bristol Myers Squibb, Genentech, Merck, Seattle Genetics, AstraZeneca, ADC Therapeutics, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, AddVie, Allogene Therapeutics. He reports research funding from: Bristol Myers Squibb, Genenetech, Merck, Seattle Genetics, KiTE Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics. CS has served as a paid consultant: Kite/a Gilead Company, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, Ono Pharmaceuticals, MorphoSys, CSL Behring, Syncopation Life Sciences, CRISPR Therapeutics and GSK. He has received research funds for clinical trials from: Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, Actinium Pharmaceuticals, Sanofi-Genzyme and NKARTA. Mehdi Hamadani reports research support/Funding: Takeda Pharmaceutical Company; ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, Abbvie, Caribou, Genmab. Speaker’s Bureau: ADC Therapeutics, AstraZeneca, BeiGene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR. AJJ reports: research funding AbbVie. The other authors reported no conflicts of interest to disclose.

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Wang, T.P., Ahn, K.W., Shadman, M. et al. Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis. Leukemia (2024). https://doi.org/10.1038/s41375-024-02242-6

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