System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Research Support, N.I.H., Intramural Research Support, N.I.H., Extramural Ppublish 18 citations

PubMed: 37821079 DOI: 10.1016/j.jtct.2023.10.006

INSPIRED Symposium Part 3: Prevention and Management of Pediatric Chimeric Antigen Receptor T Cell-Associated Emergent Toxicities.

Transplant Cell Ther 30(1):38-55

Authors: Kevin O McNerney, Emily M Hsieh, Haneen Shalabi, Rebecca Epperly, Pamela L Wolters, Joshua A Hill, Rebecca Gardner, Aimee C Talleur, Nirali N Shah, Jenna Rossoff

Affiliations

  • Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
  • Pediatric Hematology/Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Los Angeles, California.
  • Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Department of Bone Marrow Transplant, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Center, Seattle, Washington.
  • Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
  • Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.

Abstract

Chimeric antigen receptor (CAR) T cell (CAR-T) therapy has emerged as a revolutionary cancer treatment modality, particularly in children and young adults with B cell malignancies. Through clinical trials and real-world experience, much has been learned about the unique toxicity profile of CAR-T therapy. The past decade brought advances in identifying risk factors for severe inflammatory toxicities, investigating preventive measures to mitigate these toxicities, and exploring novel strategies to manage refractory and newly described toxicities, infectious risks, and delayed effects, such as cytopenias. Although much progress has been made, areas needing further improvements remain. Limited guidance exists regarding initial administration of tocilizumab with or without steroids and the management of inflammatory toxicities refractory to these treatments. There has not been widespread adoption of preventive strategies to mitigate inflammation in patients at high risk of severe toxicities, particularly children. Additionally, the majority of research related to CAR-T toxicity prevention and management has focused on adult populations, with only a few pediatric-specific studies published to date. Given that children and young adults undergoing CAR-T therapy represent a unique population with different underlying disease processes, physiology, and tolerance of toxicities than adults, it is important that studies be conducted to evaluate acute, delayed, and long-term toxicities following CAR-T therapy in this younger age group. In this pediatric-focused review, we summarize key findings on CAR-T therapy-related toxicities over the past decade, highlight emergent CAR-T toxicities, and identify areas of greatest need for ongoing research.

MeSH

Cells, Hematopoietic Stem Cell Transplantation, Receptors, Antigen, Receptors, Chimeric Antigen, Research, Therapeutics, T-Lymphocytes, Child, Receptors, Antigen, T-Cell

Cited by