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      The Burden of Invasive Fungal Disease Following Chimeric Antigen Receptor T-Cell Therapy and Strategies for Prevention

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          Abstract

          Chimeric antigen receptor (CAR) T-cell therapy is a novel immunotherapy approved for the treatment of hematologic malignancies. This therapy leads to a variety of immunologic deficits that could place patients at risk for invasive fungal disease (IFD). Studies assessing IFD in this setting are limited by inconsistent definitions and heterogeneity in prophylaxis use, although the incidence of IFD after CAR T-cell therapy, particularly for lymphoma and myeloma, appears to be low. This review evaluates the incidence of IFD after CAR T-cell therapy, and discusses optimal approaches to prevention, highlighting areas that require further study as well as future applications of cellular therapy that may impact IFD risk. As the use of CAR T-cell therapy continues to expand for hematologic malignancies, solid tumors, and most recently to include non-oncologic diseases, understanding the risk for IFD in this uniquely immunosuppressed population is imperative to prevent morbidity and mortality.

          Abstract

          Chimeric antigen receptor (CAR) T-cell therapy is a rapidly expanding novel immunotherapy for treatment of hematologic malignancies. The characteristics of invasive fungal disease after CAR T-cell therapy are not well described, but the burden in published studies has been low.

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          Most cited references121

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          Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

          In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
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            Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

            In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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              Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

              Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
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                Author and article information

                Contributors
                Journal
                Open Forum Infect Dis
                Open Forum Infect Dis
                ofid
                Open Forum Infectious Diseases
                Oxford University Press (US )
                2328-8957
                June 2024
                13 March 2024
                13 March 2024
                : 11
                : 6
                : ofae133
                Affiliations
                Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts, USA
                Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School , Boston, Massachusetts, USA
                Infectious Diseases Service, Lausanne University Hospital and University of Lausanne , Lausanne, Switzerland
                Section of Infectious Diseases and Global Health, The University of Chicago , Chicago, Illinois, USA
                Division of Infectious Diseases, University of Alabama at Birmingham , Birmingham, Alabama, USA
                Division of Infectious Diseases, University of California-Davis , Sacramento, California, USA
                Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas, M.D. Anderson Cancer Center , Houston, Texas, USA
                Division of Infectious Diseases, Medical College of Georgia/Augusta University , Augusta, Georgia, USA
                Division of Infectious Diseases, University of Maryland School of Medicine , Baltimore, Maryland, USA
                Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts, USA
                Division of Infectious Diseases, Massachusetts General Hospital , Boston, Massachusetts, USA
                Department of Medical Oncology, Massachusetts General Hospital Cancer Center , Boston, Massachusetts, USA
                Author notes
                Correspondence: Jessica S. Little, MD, Division of Infectious Diseases, Brigham and Women’s Hospital, 75 Francis St, PBB-A4, Boston, MA 02115 ( jlittle@ 123456bwh.harvard.edu ).

                Potential conflicts of interest. E. K. received grants from the Swiss National Science Foundation (grant number P500PM_202961) and SICPA Foundation. T. M. received research support from F2G, Scynexis, and Cidara. G. R. T. has performed consulting and received research support from Astellas, Cidara, Melinta, Mundipharma, F2G, Amplyx, and Pfizer, and has served on a data and safety monitoring board for Pfizer. D. P. K. reports honoraria and research support from Gilead Sciences and Astellas Pharma; received consultant fees from Astellas Pharma, Merck, Knight, and Gilead Sciences; and is a member of the data review committees of Cidara Therapeutics, AbbVie, Scynexis, and the Mycoses Study Group. J. V. has served as a consultant to Cidara, Melinta, F2G, and Scynexis and as a speaker to AbbVie and Melinta. S. P. H. received research support from F2G, Scynexis, and GSK and has served as an advisor to F2G, Melinta, Pfizer, Roche, and Seres Therapeutics. All other authors report no potential conflicts.

                Author information
                https://orcid.org/0000-0001-8093-5647
                https://orcid.org/0000-0001-8019-3073
                https://orcid.org/0000-0002-8051-2940
                https://orcid.org/0000-0002-4271-7443
                Article
                ofae133
                10.1093/ofid/ofae133
                11181190
                38887472
                09faeb0d-f04b-4aa3-8897-a2a07308c864
                © The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 December 2023
                : 01 March 2024
                : 05 March 2024
                : 17 June 2024
                Page count
                Pages: 15
                Categories
                Review Article
                AcademicSubjects/MED00290

                antifungal prophylaxis,antifungal stewardship,car t-cell therapy,immunotherapy,invasive fungal disease

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