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Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

Bone Marrow Transplantation volume 57, pages 1477–1488 (2022)Cite this article

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Abstract

CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.

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Acknowledgements

This research was supported in part by NIH/NCI Cancer Center Support Grant P30 CA008748. 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 Hematology and Research Unit in Translational Hematology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Kitsada Wudhikarn

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

    Miguel-Angel Perales

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

    Miguel-Angel Perales

Authors
  1. Kitsada Wudhikarn
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  2. Miguel-Angel Perales
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Contributions

KW generated the concept of the study, conducted the literature search, reviewed the literature, and draft the initial manuscript. MAP contributed to writing the manuscript and provided feedback on the manuscript. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Kitsada Wudhikarn.

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Competing interests

M-AP reports honoraria from Abbvie, Allovir, Astellas, Bristol-Myers Squibb, 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. KW declares no relevant conflict of interest.

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Wudhikarn, K., Perales, MA. Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy. Bone Marrow Transplant 57, 1477–1488 (2022). https://doi.org/10.1038/s41409-022-01756-w

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