Abstract 12461: Early Use of Tocilizumab Following Cytokine Release Syndrome During CAR-T Therapy for Multiple Myeloma May Be Associated With Fewer Short and Long Term Adverse Cardiovascular Events

Abstract

Background: Chimeric antigen receptor-T cell (CAR-T) therapies have recently been approved for multiple myeloma (MM). Patients with MM have a higher burden of cardiovascular (CV) disease compared to other hematologic malignancies due to higher prevalence of CV risk factors, potentially cardiotoxic therapies and older age. Retrospective studies of CAR-T therapy in other hematologic malignancies demonstrated a 20-30% CV event rate following higher grades of cytokine release syndrome (CRS). Early use of the interleukin-6 antagonist, tocilizumab, to reverse CRS has been reported to lower rates of major adverse CV events (MACE). Hypothesis: At our institution, tocilizumab is usually administered as early as grade 1 CRS. We hypothesized that our patients would have lower rates of CV toxicity compared to studies where tocilizumab was administered late or not at all. Methods: We conducted a retrospective chart review of adult patients undergoing CAR-T therapy for MM between 2017 and 2023. The primary outcome was MACE (composite of myocardial injury, new heart failure, stroke, new arrhythmias and CV death) over a median period of 12 months. A Kaplan-Meier curve was used to analyze probability of developing MACE. Results: Of the 145 patients studied, the demographics included median age of 61, male (61%), prior anthracycline use (25%), and carfilzomib use (47%) within 1 year. CV co-morbidities included 57% with hypertension, 35% hyperlipidemia, 23% diabetes mellitus type 2, 17% coronary artery disease, and 14% left ventricular dysfunction. CRS occurred in 121 (83%) patients, of which 99 had grade 1 (82%), 19 (16%) had grade 2 and 3 (2%) had grade 3. Of those with CRS, 108 (89%) received tocilizumab, on average within the first day of CRS. Within 1 year of CAR-T therapy, 14 patients (10%) experienced MACE. The Kaplan-Meier estimates for incidence of MACE were 6% at 30 days, 8% at 6 months and 11% at 12 months. Conclusion: The occurrence of MACE in MM patients following CAR-T therapy with early administration of tocilizumab was lower compared to previously published retrospective studies of CAR-T therapy for other hematologic malignancies despite high CV burden. Further prospective studies are needed to validate these findings.