Infectious complications of chimeric antigen receptor (CAR) T-cell therapies

Gea-Banacloche, Juan

doi:10.1053/j.seminhematol.2023.02.003

Cited by 7 publications

(12 citation statements)

References 77 publications

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“…Discontinuation of immunoglobulin replacement must be guided by recovery of functional B cells. 36,96,97…”

Section: Management Of Hypogammaglobulinemiamentioning

confidence: 99%

“…In the cohort of pediatric pts with B‐ALL, Deyà‐Martinez et al, observed that 71% of patients developed undetectable IgM levels at a median of 71 days after infusion 9,11,14,16–22,36,50–64,66–98 ; IgA levels decreased in 13% of patients to undetectable levels at 185 days after infusion (11–308). Patients with undetectable IgM, showed a longer CAR‐T persistence (373.5 vs. 60 days; p : <.001).…”

Section: Immune Reconstitutionmentioning

confidence: 99%

“…Intravenous or subcutaneous immunoglobulin replacement aims to maintain serum IgG levels >400 mg/dL in adults. Discontinuation of immunoglobulin replacement must be guided by recovery of functional B cells 36,96,97 …”

Section: Management Of Cytopenias and Hypogammaglobulinemiamentioning

confidence: 99%

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Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T‐cells (CAR‐T): A comprehensive review on incidence, risk factors and current management

Galli

Fresa

Bellesi

et al. 2023

European J of Haematology

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Impaired function of hematopoiesis after treatment with chimeric antigen T‐cells (CAR‐T) is a frequent finding and can interest a wide range of patients, regardless of age and underlying disease. Trilinear cytopenias, as well as hypogammaglobulinemia, B‐cell aplasia, and T‐cell impairment, can severely affect the infectious risk of CAR‐T recipients, as well as their quality of life. In this review, we provide an overview of defects in hematopoiesis after CAR‐T, starting with a summary of different definitions and thresholds. We then move to summarize the main pathogenetic mechanisms of cytopenias, and we offer insight into cytomorphological aspects, the role of clonal hematopoiesis, and the risk of secondary myeloid malignancies. Subsequently, we expose the major findings and reports on T‐cell and B‐cell quantitative and functional impairment after CAR‐T. Finally, we provide an overview of current recommendations and leading experiences regarding the management of cytopenias and defective B‐ and T‐cell function.

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“…Discontinuation of immunoglobulin replacement must be guided by recovery of functional B cells. 36,96,97…”

Section: Management Of Hypogammaglobulinemiamentioning

confidence: 99%

Section: Immune Reconstitutionmentioning

confidence: 99%

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Hematopoiesis and immune reconstitution after CD19 directed chimeric antigen receptor T‐cells (CAR‐T): A comprehensive review on incidence, risk factors and current management

Galli

Fresa

Bellesi

et al. 2023

European J of Haematology

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“…26 Infections are seen across both classes of therapies and can be a significant cause of morbidity and mortality. 27,28 In particular, severe and life-threatening infections have been observed after BCMA-BsAb therapy and may be target-specific and the result of T-cell exhaustion from continuous therapy. 27 Hypogammaglobinemia and neutropenia are significant risk factors for infections, and thus continued monitoring of levels and administration of intravenous immunoglobulin and growth factors may be necessary to adequately protect patients.…”

Section: Overview Of Toxicitymentioning

confidence: 99%

Integrating Immune Therapies for the Treatment of Multiple Myeloma

Mikkilineni,

Sidana

2023

Journal of the National Comprehensive Cancer Network

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Patients with relapsed or refractory multiple myeloma (RRMM) that is refractory to a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 antibody (triple-class refractory MM) have poor outcomes. Recently, 2 classes of T-cell engaging therapies—CAR T-cell therapy and bispecific T-cell engaging antibodies (BsAbs)—have resulted in unprecedented response rates and survival outcomes in these heavily pretreated patients. The most common targets are BCMA and GPRC5D, with other targets in development. The main classes of adverse effects include cytokine release syndrome, neurotoxicity, infections, and cytopenias, as well as adverse effects unique to specific products. As of September 2023, 2 BCMA-targeting CAR-T cell products, 2 BCMA-targeting BsAbs, and 1 GPRC5D-targeting BsAb, are FDA-approved for standard-of-care use in patients with RRMM who received at least 4 prior lines of therapy, including prior treatment with a proteasome inhibitor, an IMiD, and an anti-CD38 antibody. Earlier-line use is under investigation and has shown promising results. Several other investigational CAR-T constructs and bispecific antibodies are in clinical development. As these therapies become more widely used, including in earlier-line setting, efforts to understand optimal sequencing and mitigate toxicities remain critical.

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“…Furthermore, CAR T cells can induce a range of specific adverse events, such as cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, and the use of immunosuppressives for the management of these treatment-associated toxicities enhances the global immunodeficiency and associated infection risk observed in CAR T-cell recipients [ 11 , 12 ]. As the indication for CAR T-cell therapy expands beyond relapsed/refractory B-cell malignancies to include refractory multiple myeloma, the spectrum and risk of infectious complications are expected to evolve [ 13 ]. Considering the heterogeneous nature of CAR T-cell recipients, individual patient characteristics become vital in assessing the infectious risk associated with this innovative therapy [ 12 ].…”

mentioning

confidence: 99%