(231) Time to Resolution of Grade 1 Cytokine Release Syndrome With or Without Interleukin-6 Receptor Antagonist Therapy

Poster Abstract:

Background: Cytokine release syndrome (CRS) is a toxicity of chimeric antigen receptor T-cell (CAR T) and bispecific T-cell engager (BiTE) therapies characterized by fever and, in more severe cases, hypotension and hypoxia.(1) It is currently unknown if tocilizumab, an interleukin-6 receptor antagonist, hastens resolution of American Society for Transplantation and Cellular Therapy (ASTCT) grade 1 CRS symptoms or if tocilizumab should be reserved for grade 2-4 CRS. (2-3) This study retrospectively evaluated outcomes of patients who did or did not receive tocilizumab for grade 1 CRS to elucidate the role of IL-6 receptor antagonism in this setting.
Objective(s): The primary objective of this study was to determine if there was a difference in time to CRS resolution in patients with grade 1 CRS who did or did not receive tocilizumab during grade 1 CRS.

Methods: This single-center, retrospective, cohort study included patients ≥18 years old admitted for ≥1 episode of grade 1 CRS between 2017-2023. An episode of grade 1 CRS was defined as an initial presentation with a temperature of ≥100.4°F without grade 2-4 CRS features. CRS resolution was defined as time to grade 0 CRS that subsequently persisted for 24 hours. Commercially-available and investigational therapies were included. Patients were identified and data were collected through institutional medication use and investigational drug databases and chart review.

Results: 45 patients receiving commercially-available products and 95 patients receiving investigational products were evaluated for inclusion. Among patients receiving commercially-available products, 22 patients with 26 episodes of grade 1 CRS met inclusion criteria. 13 (50%) episodes of grade 1 CRS were treated with tocilizumab during grade 1 CRS, 7 episodes (27%) were treated with tocilizumab upon progression to grade 2 or higher CRS, and 6 episodes (23%) were not treated with tocilizumab. Mean time to CRS resolution was 52.8 hours in grade 1 CRS episodes that were treated with tocilizumab, 52.9 hours in episodes that were treated with tocilizumab upon progression to grade 2 or higher CRS, and 16.1 hours in episodes that were not treated with tocilizumab.
Discussion/

Conclusions: Preliminary results show similar time to CRS resolution in patients who received tocilizumab during grade 1 CRS compared to those who received tocilizumab upon progression to grade 2 or higher CRS. Patients who were not treated with tocilizumab had the shortest time to CRS resolution; however, this result was confounded by a high percentage of patients receiving therapies that cause less severe CRS.

References (must also be included in final poster): 1.Lee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of Blood and Marrow Transplantation. 2019;25(4):625-638. doi:10.1016/j.bbmt.2018.12.758
2.Banerjee R, Fakhri B, Shah N. Toci or not toci: innovations in the diagnosis, prevention, and early management of cytokine release syndrome. Leukemia & Lymphoma. 2021;62(11):2600-2611. doi:10.1080/10428194.2021.1924370
3. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148.