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Fungal Infections Associated with CD19-Targeted Chimeric Antigen Receptor T Cell Therapy

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Abstract 

Purpose of Review

This review focuses on the epidemiology of fungal infections after CD19-targeted chimeric antigen receptor (CAR) T cell therapy and associated risk factors for their development and describes infectious disease screenings and antifungal prophylactic strategies.

Recent Findings

Epidemiologic studies characterizing fungal infections in patients with hematologic malignancies treated with CD19-targeted CAR T cell therapy are scarce. Fungal infections occur in approximately 2–13% of CAR T cell recipients, both early and late after infusion. Candida, Aspergillus, and Pneumocystis are the most common culprit pathogens. Invasive fungal infections seldom contribute to mortality. While various risk factors for the development of fungal infections have been proposed, all relate to dysregulation in innate and adaptive immunity. Exposure to areas where endemic fungi are known to be present in the environment may also be a risk factor. Infectious disease screenings and prophylactic strategies vary broadly across institutions.

Summary

Although data are limited, fungal infections occur in a small proportion of patients after CD19-targeted CAR T cell therapy. Additional studies are needed to better describe fungal infection epidemiology, individualize infectious disease screenings, and inform antifungal prophylaxis in this population.

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Author notes

  1. Charles Gaulin and Zoey Harris contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic, 5777 E Mayo Boulevard, Phoenix, AZ, 85054, USA

    Charles Gaulin, Zoey Harris & Javier Muñoz

  2. Division of Infectious Diseases, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Rich Kodama & Monika Shah

  3. Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Phoenix, AZ, USA

    Janis Blair

  4. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Yucai Wang & Yi Lin

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Dr. Gaulin reports personal fees from DeciBio, outside the submitted work. Dr. Harris has nothing to disclose. Dr. Kodama has nothing to disclose. Dr. Shah has nothing to disclose. Dr. Blair has nothing to disclose. Dr. Wang reports grants and personal fees from lncyte, grants and personal fees from lnnoCare, grants and personal fees from Loxo Oncology, grants and personal fees from Eli Lilly, grants from MorphoSys, grants from Novartis, grants from Genentech, grants from Genmab, personal fees from TG Therapeutics, personal fees from Kite, personal fees from Jansen, and personal fees from BeiGene, outside the submitted work. Dr. Lin reports grants and personal fees from Kite/Gilead, grants and personal fees from Celgene/BMS, personal fees from Juno/BMS, grants and personal fees from bluebird bio, grants and personal fees from Janssen, grants and personal fees from Legend Biotech, personal fees from Gamida Cells, personal fees from Novartis, personal fees from Iovance, personal fees from Takeda, personal fees from Fosun Kite, personal fees and other from Pfizer, grants from Merck, grants from Boston Scientific, other from Sorrento, and other from NexImmune, outside the submitted work. Dr. Munoz reports grants and personal fees from Pharmacyclics/AbbVie, grants and personal fees from Bayer, grants and personal fees from Gilead/Kite Pharma, personal fees from Pfizer, grants and personal fees from Janssen, personal fees from Juno/Celgene, personal fees from BMS, personal fees from Kyowa, personal fees from Alexion, personal fees from Fosun Kite, personal fees from Innovent, grants and personal fees from Seattle Genetics, personal fees from Debiopharm, personal fees from Karyopharm, personal fees from Genmab, personal fees from ADC Therapeutics, personal fees from Epizyme, personal fees from BeiGene, personal fees from Servier, personal fees from Novartis, personal fees from MorphoSys/Incyte, personal fees from Secura Bio, personal fees from TG Therapeutics, personal fees from MEI, personal fees from Lilly/Loxo, grants from Celgene, grants from Merck, grants from Portola, grants from Incyte, grants from Genentech, grants from Millennium, personal fees from Targeted Oncology, personal fees from OncView, personal fees from Curio, personal fees from Physicians’ Education Resource, personal fees from Pharmacyclics/Janssen, personal fees from Acrotech/Aurobindo, personal fees from Pharmacyclics, personal fees from Verastem, personal fees from AstraZeneca, personal fees from Celgene/BMS, and personal fees from Genentech/Roche, outside the submitted work.

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Gaulin, C., Harris, Z., Kodama, R. et al. Fungal Infections Associated with CD19-Targeted Chimeric Antigen Receptor T Cell Therapy. Curr Fungal Infect Rep 17, 87–97 (2023). https://doi.org/10.1007/s12281-023-00460-6

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