Efficacy of tocilizumab in resolving chimeric antigen receptor T-cell (CAR T)–induced cytokine release syndrome (CRS): A pooled clinical trial (CT) analysis of patients (pts) with B-cell lymphoma (BCL).

7027 Background: CAR T therapy offers significant efficacy in the treatment of relapsed/refractory hematologic malignancies but is also associated with developing immune-mediated toxicity, such as CRS. Tocilizumab, an interleukin-6 receptor antagonist, is the only FDA-approved treatment for CAR T-induced CRS, but its efficacy in large pt populations remains limited. This study aims to evaluate the efficacy of tocilizumab by assessing complete response (CR) rates and median time-to-CR in pts with BCL experiencing CAR T-induced CRS, using pooled clinical trial data. Methods: We pooled aggregated, anonymized data made available through Medidata Clinical Cloud across 2 doses of tocilizumab, rescue therapy with siltuximab, CRS grade escalation after 2 tocilizumab doses, or CRS recurrence after 2 tocilizumab doses. The CRS events were graded using Lee's Criteria 2014. CR rate was described as a proportion, and time-to-CR was estimated using the Kaplan-Meier method. Results: Of the 2,304 pts included in the database, 680 met the inclusion criteria (37% aged ≥ 65 yrs; 63% male; 80% white; 47% Diffuse Large BCL, 14% Follicular Lymphoma 49% Eastern Cooperative Oncology Group (ECOG) performance score=0 48% Ann Arbor Stage IV; 27% had bulky disease; 65% without bridging therapy; 73% received CD28 costimulatory domain-targeted CAR T-infusion, 27% received 41bb costimulatory domain-targeted CAR T-infusion; 72% with grade 1 CRS at the time of onset). The median time from CAR-T infusion to CRS onset was 2 days (IQR: 1 - 4), and the median time from CRS onset to the first dose of tocilizumab was 2 days (IQR: 1 - 3). The CR rate was 66% (95% CI: 62.5% - 69.6%) and the median time to CR was 4 days (95% CI: 3 - 4), with 35% achieving CR in ≤ 2 days and 80% in ≤ 7 days. Conclusions: This large-sample pt-level study of pooled CT data showed significant efficacy of tocilizumab in resolving CAR T-induced CRS among pts with BCL, with two-thirds of pts achieving CR. The rapid median time-to-CR (4 days) underscores the role of tocilizumab as a first-line intervention. However, the 34% of pts who did not meet the CR criteria suggest a need for further investigation into other treatment strategies.