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Management of prolonged cytopenia following CAR T-cell therapy

Bone Marrow Transplantation volume 57, pages 1839–1841 (2022)Cite this article

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The approval of CD19-targeted chimeric receptor-modified T cell (CAR T-cell) therapy has transformed the outcomes of relapsed/refractory (R/R) non-Hodgkin B-cell lymphomas. Reported overall responses (ORR) range from 52 to 88%, with complete response (CR) rates of 40–59% [1,2,3,4]. While effective, CD19 CAR T-cells are associated with unique toxicities, including cytopenias [5]. In the JULIET trial, 32% of patients had grade 3 or 4 thrombocytopenia and/or neutropenia that were not resolved by day +28 of CAR T-cell infusion [2]. In ZUMA-1 trial, 17% of the patients had grade 3 or worse cytopenias three months after CAR T-cell therapy [3].

The mechanism of prolonged cytopenia is not well characterized. Currently, management of severe cytopenias after CAR T-cell therapy involves transfusion support [6, 7]. Thrombopoietin analogs have been approved for cytopenias related to immune thrombocytopenia (ITP) [8], aplastic anemia [9] and poor graft function after stem cell transplant [10], but their role in post-CART T-cell cytopenias is unknown.

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Fig. 1: Patient’ response to Romiplostim treatment.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

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

    Magdalena Corona, Roni Shouval, Ana Alarcón, Michael Scordo, Gunjan Shah, Miguel-Ángel Perales & Parastoo B. Dahi

  2. Hematology and Hemotherapy Service, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Magdalena Corona

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

    Roni Shouval, Connie Batlevi, Maria Lia Palomba, Michael Scordo, Gunjan Shah, Miguel-Ángel Perales & Parastoo B. Dahi

  4. Hematology and Hemotherapy Service, Hospital Universitario Gregorio Marañón, Madrid, Spain

    Ana Alarcón

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

    Jessica Flynn & Sean Devlin

  6. Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Connie Batlevi & Maria Lia Palomba

  7. Hematology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Simon Mantha

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

    Craig Sauter

Authors
  1. Magdalena Corona
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  11. Craig Sauter
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Contributions

All authors designed and conceptualized the project. MC, AA and RS collected the data. All authors wrote and edited the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Parastoo B. Dahi.

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Competing interests

RS- consultancy to Medxus and MyBiotics. MAP- honoraria from Abbvie, Allovir, Astellas, Bristol-Myers Squibb, Caribou Biosciences, Celgene, Equilium, Exevir, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, OrcaBio, Takeda, and VectivBio AG, Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros. He has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. He serves in a volunteer capacity as a member of the Board of Directors of the American Society for Transplantation and Cellular Therapy (ASTCT) and on the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Executive Committee, and previously served on the Board of Directors of Be The Match (National Marrow Donor Program, NMDP). GS- research funding to the institution from Janssen, Amgen and Beyond Spring.

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Corona, M., Shouval, R., Alarcón, A. et al. Management of prolonged cytopenia following CAR T-cell therapy. Bone Marrow Transplant 57, 1839–1841 (2022). https://doi.org/10.1038/s41409-022-01771-x

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