Beyond Cytokine Storm: Subacute Toxicities and Long-Term Monitoring Needs in Paediatric CAR-T
A multicentre expert review identifies six key areas requiring extended monitoring after paediatric CAR-T therapy: neurocognitive function, psychosocial health, immune reconstitution, organ toxicities, subsequent neoplasms, and remission durability. The authors propose systematic frameworks for laboratory surveillance including immunoglobulin levels, lymphocyte subset analysis by flow cytometry, and infection biomarker panels to guide long-term follow-up protocols.
The original study
Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells.
- Authors
- Shalabi H, Gust J, Taraseviciute A, Wolters PL, Leahy AB, Sandi C, et al.
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Review
- PMID
- 33495553
Original 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 CAR 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.