Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome Following Axicabtagene Ciloleucel or Brexucabtagene Autoleucel Chimeric Antigen Receptor T-Cell Therapy: Center for International Blood and Marrow Transplant Research Data.
BACKGROUND Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 have demonstrated effectiveness in the treatment of relapsed/refractory B-cell malignancies. Several CAR-T therapies have been approved in the United States, including axicabtagene ciloleucel (axi-cel), for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and brexucabtagene autoleucel (brexu-cel), for B-cell precursor acute lymphoblastic leukemia and mantle cell lymphoma (MCL). However, use of CAR-T therapies can result in potentially severe adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). OBJECTIVE This analysis of real-world data evaluated the incidence and management of CRS and ICANS in patients with B-cell malignancies following treatment with axi-cel or brexu-cel therapy. STUDY DESIGN This retrospective observational cohort study analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult patients in the United States who received axi-cel or brexu-cel for any indication from October 2020 to December 2021 with ≥1 follow-up visit were included. The main outcome of interest was incidence of CRS and ICANS following CAR-T therapy, graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Management of CRS and ICANS with preventive therapies and treatments administered following development of CRS and ICANS was also investigated. RESULTS Overall, 927 patients across 87 US centers were included (axi-cel, n=707 [76.3%]; brexu-cel, n=220 [23.7%]). Median (range) age was 63 (19-89) years, and 65.3% (605/927) were male. Most patients (83.3% [n=589]) received axi-cel for diffuse large B-cell lymphoma or transformed follicular lymphoma. All patients who received brexu-cel had mantle cell lymphoma. Overall, 766 (82.6%) patients developed CRS (grade ≥2, 47.0%; 360/766). Of patients with available data, 12.4% (89/715) received CRS preventive therapy, most commonly with tocilizumab alone (79.8%; 71/89). Of patients who developed CRS, 76.6% (587/766) received CRS treatment, including 63.5% (258/406) of patients with grade 1 and 91.4% (329/360) with grade ≥2. The most common treatment was tocilizumab (97.3%; 571/587), alone or in combination. Of patients with available data, 49.8% (356/715) received ICANS prevention, mostly anti-epileptics alone (93.3%; 332/356). Of 876 evaluable patients, 424 (48.4%) developed ICANS (grade ≥2, 71.5%; 303/424). Of these, 85.6% (363/424) received treatment for ICANS, most commonly corticosteroids (92.3%; 335/363). CONCLUSIONS Rates of CRS (82.6%) and ICANS (48.4%) were consistent with incidences expected based on prescribing information for axi-cel and brexu-cel, highlighting potential burdens of CAR-T therapy. These results also stress the importance of continuous patient monitoring and management during CAR-T therapy and demonstrate an evolving treatment landscape, including more aggressive management of CRS and interest in preventive therapies for CRS and ICANS.