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).

Abstract

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 <10 multinational CTs, comprising 2,304 patients. Inclusion criteria required a BCL diagnosis, who developed CAR T-induced CRS and were treated with tocilizumab. The index date was defined as the initiation of tocilizumab. CR was defined as CRS resolution within 14 days of the index date without meeting any failure to respond criteria. Non-response was defined as requiring>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 & 13% Mantle Cell Lymphoma; 49% Eastern Cooperative Oncology Group (ECOG) performance score=0 & 49% ECOG=1; 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.