Safety and Toxicity Profiles of CAR T Cell Therapy in Non-Hodgkin Lymphoma: A Systematic Review and Meta-Analysis

CAR T cell therapy has improved outcomes for patients with NHL with varied and unpredictable toxicity. In this systematic review and meta-analysis, we found that rates of CRS and ICANS were significantly higher with axi-cel as compared to both liso-cel and tisa-cel and that rates of all-grade and severe neutropenia were significantly greater with liso-cel. By better understanding and predicting toxicities, it may become possible to tailor therapies towards individual patients and further improve outcomes. Background: The application of CD19-directed chimeric antigen receptor T (CAR T) cell therapy has improved outcomes for thousands of patients with non-Hodgkin B cell lymphoma (NHL). The toxicities associated with various CAR T cell products, however, can be severe and difficult to anticipate. Methods: In this systematic review and metaanalysis, we set out to determine whether there are measurable differences in common toxicities, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), cytopenias, and infections, between CAR T products that are commercially available for the treatment of NHL. Results: After a stringent study selection process, we used a cohort of 1364 patients enrolled in 15 prospective clinical trials investigating the use of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). We found that the rates of CRS and ICANS were significantly higher with axi-cel as compared to both liso-cel and tisa-cel. Conversely, we demonstrated that rates of all-grade and severe neutropenia were significantly greater with liso-cel. Febrile neutropenia and all-grade infection rates did not differ significantly between products though rates of severe infection were increased with axi-cel. Conclusions: Overall, this study serves as the first to delineate toxicity profiles associated with various available CAR T products. By better understanding associated toxicities, it may become possible to tailor therapies towards individual patients and anticipate the development of toxicities at earlier stages.