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Publications

Journal Article Review Research Support, Non-U.S. Gov't Ppublish 25 citations

PubMed: 38861351 DOI: 10.1182/bloodadvances.2024013044

CAR T-cell toxicities: from bedside to bench, how novel toxicities inform laboratory investigations.

Blood Adv 8(16):4348-4358

Authors: Fabiana Perna, Samir Parekh, Caroline Diorio, Melody Smith, Marion Subklewe, Rakesh Mehta, Frederick L Locke, Nirali N Shah

Affiliations

  • Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL.
  • Division of Hematology and Medical Oncology, The Tish Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA.
  • Department of Medicine, Stanford University, Stanford, CA.
  • Department of Medicine III, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
  • Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
  • Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD.

Abstract

Multiple chimeric antigen receptor (CAR) T-cell therapies are US Food and Drug Administration-approved, and several are under development. Although effective for some cancers, toxicities remain a limitation. The most common toxicities, that is, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, are well described. With increasing utilization, providers worldwide are reporting other emergent and often complicated toxicities. Given the evolving toxicity profiles and urgent need to catalog these emerging and emergent CAR T-cell toxicities and describe management approaches, the American Society of Hematology Subcommittee on Emerging Gene and Cell Therapies organized the first scientific workshop on CAR T-cell toxicities during the annual society meeting. The workshop functioned to (1) aggregate reports of CAR T-cell emergent toxicities, including movement disorders after B-cell maturation antigen CAR T cell, coagulation abnormalities, and prolonged cytopenia; (2) disseminate bedside-to-bench efforts elucidating pathophysiological mechanisms of CAR T-cell toxicities, including the intestinal microbiota and systemic immune dysregulation; and (3) highlight gaps in the availability of clinical tests, such as cytokine measurements, which could be used to expand our knowledge around the monitoring of toxicities. Key themes emerged. First, although clinical manifestations may develop before the pathophysiologic mechanisms are understood, they must be studied to aid in the detection and prevention of such toxicities. Second, systemic immune dysregulation appears to be central to these emergent toxicities, and research is needed to elucidate the links between tumors, CAR T cells, and microbiota. Finally, there was a consensus around the urgency to create a repository to capture emergent CAR T-cell toxicities and the real-world management.

MeSH

Cytokines, Cells, Laboratories, Neoplasms, T-Lymphocytes, Hematologic Diseases, Microbiota, Car-T Cell

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