Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells.

TitleBeyond the storm - subacute toxicities and late effects in children receiving CAR T cells.
Publication TypeJournal Article
Year of Publication2021
AuthorsShalabi H, Gust J, Taraseviciute A, Wolters PL, Leahy AB, Sandi C, Laetsch TW, Wiener L, Gardner RA, Nussenblatt V, Hill JA, Curran KJ, Olson TS, Annesley C, Wang H-W, Khan J, Pasquini MC, Duncan CN, Grupp SA, Pulsipher MA, Shah NN
JournalNat Rev Clin Oncol
Date Published2021 Jan 25
ISSN1759-4782
Abstract

As clinical advances with chimeric antigen receptor (CAR) T cells are increasingly described and the potential for extending their therapeutic benefit grows, optimizing the implementation of this therapeutic modality is imperative. The recognition and management of cytokine release syndrome (CRS) marked a milestone in this field; however, beyond the understanding gained in treating CRS, a host of additional toxicities and/or potential late effects of CAR T cell therapy warrant further investigation. A multicentre initiative involving experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation was convened to facilitate the comprehensive study of extended CARĀ T cell-mediated toxicities and establish a framework for new systematic investigations of CAR T cell-related adverse events. Together, this group identified six key focus areas: extended monitoring of neurotoxicity and neurocognitive function, psychosocial considerations, infection and immune reconstitution, other end organ toxicities, evaluation of subsequent neoplasms, and strategies to optimize remission durability. Herein, we present the current understanding, gaps in knowledge and future directions of research addressing these CAR T cell-related outcomes. This systematic framework to study extended toxicities and optimization strategies will facilitate the translation of acquired experience and knowledge for optimal application of CAR T cell therapies.

DOI10.1038/s41571-020-00456-y
Alternate JournalNat Rev Clin Oncol
PubMed ID33495553