Real-World Trends of Cytokine Release Syndrome and Neurologic Events, and Pattern of Their Management Among Patients Receiving Axicabtagene Ciloleucel for Relapsed or Refractory (r/r) Large B-Cell Lymphoma (LBCL) in the US: A CIBMTR Report

• Published in: Blood 2024-11, Vol.144, p.527-527
• Main Authors: Wang, Jiasheng, Bhaskar, Shakthi, Adedokun, Babatunde, Oluwole, Olalekan O., Metheny, Leland, Moskop, Amy, Jacobson, Caron A., Shouse, Geoffrey, Ahmed, Sairah, Ghobadi, Armin, Dahiya, Saurabh, Yan, Jiali, Hu, Zhen-Huan, Best, Timothy, Kim, Jenny J., Mirjah, Debbie L., Pasquini, Marcelo C., Locke, Frederick L.
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-209093

Background Axicabtagene ciloleucel (axi-cel) is an autologous CD19-targeting CAR T-cell product that has demonstrated curative potential for r/r LBCL (Neelapu et al 2023). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are early adverse events (AEs) that could occur after axi-cel infusion. The management of these toxicities has improved over the years with early use of corticosteroids and tocilizumab, and use of prophylactic corticosteroids (Topp et al 2021; Oluwole et al 2021). As a result, the toxicity profile may change over time. Here, we investigated real-world trends in CRS and ICANS associated with axi-cel use for r/r LBCL and patterns of their management in the US from 2017 to 2023. Methods Patients who received commercial axi-cel for third line or later r/r LBCL from October 2017− July 2023 were selected from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Patients with prior non-transplant cellular therapy or primary central nervous system lymphoma were excluded. Incidences of CRS and ICANS, their maximum grades (ASTCT criteria), treatments, and durations were compared across three periods: 2017-2019, 2020-2021, and 2022-2023 (prophylactic therapy data was unavailable in 2017-2019). Multivariable regressions were conducted for dichotomous and time to event outcomes with period as the main effect while adjusting for patient-, disease-, and treatment-related covariates. Other AEs included prolonged neutropenia, prolonged thrombocytopenia, and clinically significant infections. Results A total of 1615 patients from 109 centers received axi-cel, with 923 treated during 2017-2019, 486 during 2020-2021, and 206 during 2022-2023. The median (min, max) age at infusion was 61.6 years (19.6, 90.8), 63.1 years (21.4, 84.4), and 63.2 years (19.9, 85.5), respectively. For the three respective time periods, 36%, 35%, and 35% received 4 or more lines of prior therapy, and 30%, 21%, and 19% had prior hematopoietic cell transplantation, respectively. Use of bridging therapy between leukapheresis and infusion was 34%, 42%, and 58%, while the median (interquartile range [IQR]) time from leukapheresis to infusion was 27 (25-31), 28 (26-33), and 31 (27-35) days, respectively. Prophylactic medications for CRS or ICANS were used in 50% and 62% of patients during 2020-2021 and 2022-2023, respectively. For the three respective time periods, the incidence of CRS of any grade was 83%,