Infectious Complications of Chimeric Antigen Receptor (CAR) T-cell Therapies

Overview

Journal Semin Hematol

Specialty Hematology

Date 2023 Apr 20

PMID 37080711

Authors

Juan C Gea-Banacloche

Affiliations

Soon will be listed here.

Abstract

CAR T-cells have revolutionized the treatment of many hematological malignancies. Thousands of patients with lymphoma, acute lymphoblastic leukemia, and multiple myeloma have received this "living medicine" and achieved durable remissions. Their place in therapy continues to evolve, and there is ongoing development of new generation CAR constructs, CAR T-cells against solid tumors and CAR T-cells against chronic infections like human immunodeficiency virus and hepatitis B. A significant fraction of CAR T-cell recipients, unfortunately, develop infections. This is in part due to factors intrinsic to the patient, but also to the treatment, which requires lymphodepletion (LD), causes neutropenia and hypogammaglobulinemia and necessarily increases the state of immunosuppression of the patient. The goal of this review is to present the infectious complications of CAR T-cell therapy, explain their temporal course and risk factors, and provide recommendations for their prevention, diagnosis, and management.

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References

Paul F, Vicente C, Courbon C, Moreau A, Picard M, Pochon C . [Prevention and management of infections in patients undergoing CAR T-cell therapy: Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Bull Cancer. 2021; 108(12S):S90-S97. DOI: 10.1016/j.bulcan.2021.11.001. View

Hill J, Seo S . How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood. 2020; 136(8):925-935. PMC: 7441168. DOI: 10.1182/blood.2019004000. View

Fusaroli M, Isgro V, Cutroneo P, Ferrajolo C, Cirillo V, Del Bufalo F . Post-Marketing Surveillance of CAR-T-Cell Therapies: Analysis of the FDA Adverse Event Reporting System (FAERS) Database. Drug Saf. 2022; 45(8):891-908. PMC: 9360149. DOI: 10.1007/s40264-022-01194-z. View

Mian A, Andrapalliyal N, Weathers A, Pohlman B, Hill B . Late occurrence of progressive multifocal leukoencephalopathy after anti-CD19 chimeric antigen receptor T-cell therapy. Eur J Haematol. 2021; 106(4):584-588. DOI: 10.1111/ejh.13583. View

Hayden P, Roddie C, Bader P, Basak G, Bonig H, Bonini C . Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European.... Ann Oncol. 2021; 33(3):259-275. DOI: 10.1016/j.annonc.2021.12.003. View

Marzolini M, Jaunmuktane Z, Roddie C, OReilly M, Chiodini P, Peggs K . Toxoplasmosis initially presenting as neurological sequelae of chimeric antigen receptor T-cell therapy. Lancet Infect Dis. 2019; 19(7):788. DOI: 10.1016/S1473-3099(19)30119-7. View

Maude S, Laetsch T, Buechner J, Rives S, Boyer M, Bittencourt H . Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378(5):439-448. PMC: 5996391. DOI: 10.1056/NEJMoa1709866. View

Berdeja J, Madduri D, Usmani S, Jakubowiak A, Agha M, Cohen A . Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021; 398(10297):314-324. DOI: 10.1016/S0140-6736(21)00933-8. View

Miller K, Johnson P, Abramson J, Soumerai J, Yee A, Branagan A . Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma. Blood Cancer J. 2022; 12(10):146. PMC: 9622902. DOI: 10.1038/s41408-022-00741-2. View

10.

Laetsch T, Maude S, Rives S, Hiramatsu H, Bittencourt H, Bader P . Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial. J Clin Oncol. 2022; 41(9):1664-1669. PMC: 10022844. DOI: 10.1200/JCO.22.00642. View

11.

Luo W, Li C, Zhang Y, Du M, Kou H, Lu C . Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis. BMC Cancer. 2022; 22(1):98. PMC: 8785493. DOI: 10.1186/s12885-021-09102-x. View

12.

Logue J, Zucchetti E, Bachmeier C, Krivenko G, Larson V, Ninh D . Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica. 2020; 106(4):978-986. PMC: 8017820. DOI: 10.3324/haematol.2019.238634. View

13.

Wei J, Zhu X, Mao X, Huang L, Meng F, Zhou J . Severe early hepatitis B reactivation in a patient receiving anti-CD19 and anti-CD22 CAR T cells for the treatment of diffuse large B-cell lymphoma. J Immunother Cancer. 2019; 7(1):315. PMC: 6868854. DOI: 10.1186/s40425-019-0790-y. View

14.

Sdrimas K, Diaz-Paez M, Camargo J, Lekakis L . Progressive multifocal leukoencephalopathy after CAR T therapy. Int J Hematol. 2020; 112(1):118-121. DOI: 10.1007/s12185-020-02840-x. View

15.

Little J, Aleissa M, Beluch K, Gonzalez-Bocco I, Marty F, Manne-Goehler J . Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma. Blood Adv. 2022; 6(16):4821-4830. PMC: 9631654. DOI: 10.1182/bloodadvances.2022007474. View

16.

Abramson J, Palomba M, Gordon L, Lunning M, Wang M, Arnason J . Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396(10254):839-852. DOI: 10.1016/S0140-6736(20)31366-0. View

17.

Haidar G, Nguyen M, Samanta P . Reply to Lewis and Kontoyiannis. Clin Infect Dis. 2020; 71(7):1803-1804. DOI: 10.1093/cid/ciaa032. View

18.

Strati P, Nastoupil L, Fayad L, Samaniego F, Adkins S, Neelapu S . Safety of CAR T-cell therapy in patients with B-cell lymphoma and chronic hepatitis B or C virus infection. Blood. 2019; 133(26):2800-2802. PMC: 7265784. DOI: 10.1182/blood.2019000888. View

19.

Jacobson C, Chavez J, Sehgal A, William B, Munoz J, Salles G . Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2021; 23(1):91-103. DOI: 10.1016/S1470-2045(21)00591-X. View

20.

Luo H, Wang N, Huang L, Zhou X, Jin J, Li C . Inflammatory signatures for quick diagnosis of life-threatening infection during the CAR T-cell therapy. J Immunother Cancer. 2019; 7(1):271. PMC: 6806557. DOI: 10.1186/s40425-019-0767-x. View