Early Time-to-Tocilizumab after BCMA-Directed CAR-T Therapy in Myeloma

Structured Abstract BACKGROUND Preemptive administration of tocilizumab (toci) to manage cytokine release syndrome (CRS) after chimeric antigen receptor T-cell (CAR-T) therapy may reduce rates of serious CRS but conversely may worsen neurotoxicity or risk of infections. Optimal toci administration strategies for patients with relapsed/refractory multiple myeloma (RRMM) receiving B-cell maturation antigen (BCMA)-directed CAR-T therapies have not been evaluated. OBJECTIVE To identify whether shorter time-to-toci intervals (hours between first fever attributed to CRS and first dose of toci) have any impact on therapy-related toxicities or clinical outcomes among patients with RRMM receiving BCMA-directed CAR-T therapies. STUDY DESIGN We retrospectively analyzed our institution's experience with four BCMA-directed CAR-T therapies (idecabtagene vicleucel, bb21217, ciltacabtagene autoleucel, and orvacabtagene autoceucel) for RRMM over a three-year period ending in June 2020. We divided patients based on the administration of toci and median time-to-toci interval into early toci (time-to-toci ≤ 50th percentile), late toci (time-to-toci > 50th percentile), and no-toci (no toci received) groups. We compared the early-toci and late-toci groups with regard to patient characteristics, weight-based CAR-T toxicities, selected toxicities (CRS, neurotoxicity, Macrophage Activation Syndrome, or infections), and clinical outcomes. RESULTS Of 50 analyzed patients with median follow-up 15.3 months, 76% (n = 38) received ≥ 1 dose of toci (range: 1-3) and were classified into early-toci (time-to-toci ≤ 12 hours) or late-toci (time-to-toci > 12 hours) groups. The two groups (n = 19 each) had similar CRS grade distributions, hours to CRS onset, CRS-related biomarkers, and incidences of neurotoxicity or severe infections; however, weight-adjusted CAR-T cell doses were higher in the early-toci group (median 5.99 versus 3.80 × 106 cells/kg, p CONCLUSIONS While limited by small sample size and known confounders such as CAR-T cell dose, our analysis suggests that preemptive toci strategies for CRS management with BCMA-directed CAR-T therapy – specifically, toci administration within 12 hours of the first fever attributed to CRS – do not appear to increase rates of therapy-related toxicities or compromise efficacy. However, total CRS duration may be shorter with early-toci workflows. Prospective validation of our findings may lead to improved safety and cost-effectiveness profiles for CAR-T therapy in RRMM.