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

Chimeric antigen receptor (CAR) T cell 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 cell therapy. Over the past decade, advancements have been made in identifying risk factors for severe inflammatory toxicities, investigating preventative measures to mitigate these toxicities, and exploring novel strategies to manage refractory and newly described toxicities, infectious risks, and delayed effects such as cytopenias. While much progress has been made, there remain areas for which further improvements are needed. Limited guidance exists regarding initial administration of tocilizumab +/- steroids or the management of inflammatory toxicities refractory to these treatments. There has not been widespread adoption of preventative strategies to mitigate inflammation in patients at high risk of severe toxicities, particularly in 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 in the literature. Given that children and young adults undergoing CAR T cell therapy represent a unique population with different underlying disease processes, physiology, and tolerance of toxicities than adults, it is important that studies are conducted to evaluate acute, delayed, and long-term toxicities following CAR T cell therapy in this younger age group. In the following pediatric-focused review, we summarize key findings of CAR T cell-related toxicities over the past decade, highlight emergent CAR T cell toxicities, and identify areas of greatest need for ongoing research.