Relationship between early use of tocilizumab during chimeric antigen receptor T-cell therapy for multiple myeloma and cardiovascular risk and progression-free survival.

Background: Chimeric antigen receptor-T-cell (CAR-T) therapies are approved for refractory and relapsed multiple myeloma (MM). Patients with MM have high cardiovascular disease burden due to age and cardiotoxic treatments. Retrospective studies in patients who develop severe grades of cytokine release syndrome (CRS) demonstrated a 20-30% major cardiovascular adverse event (MACE) rate. Early use of an interleukin-6 receptor antagonist, tocilizumab, to reverse CRS may lower rates of MACE. Aims: This observational study sought to examine the relationship between early use of tocilizumab and the development of MACE. Methods: We performed a retrospective chart review of adults undergoing CAR-T therapy for MM between 2017 and 2023 at a single medical center. Major cardiovascular adverse event was defined as a composite of myocardial injury, heart failure, stroke, arrhythmias, and cardiovascular death over a median period of 12 months. The secondary outcomes were progression-free survival (PFS) and overall survival (OS). Major cardiovascular adverse event incidence was estimated using the cumulative incidence function with non-cardiovascular death as a competing risk and compared by Gray's test, and PFS/OS were analysed using Kaplan-Meier methods with log-rank tests. Results: Of the 145 patients studied, CRS occurred in 120 patients (82%). Of those with CRS, 107 (89%) received tocilizumab within 24 h. Within 1 year of therapy, 14 patients (9.7%) experienced MACE. Only patients with CRS developed MACE. The incidence of MACE was 8% [95% confidence interval (CI): 5%, 14%] at 6 months and 11% (95% CI: 7%, 19%) at 12 months. Progression-free survival at 12 months was 58% (95% CI: 50%, 68%). Conclusions: Progression-free survival and OS did not differ significantly based on incidence on CRS.