Abstract 10860: Cardiotoxicity as an Adverse Effect of Immunomodulatory Drugs and Proteasome Inhibitors in Multiple Myeloma: A Meta-Analysis of Randomized Clinical Trials

Abstract

Introduction: Combination therapy of Immunomodulatory drugs (iMiDs) (Thalidomide, Lenalidomide, Pomalidomide) and Proteasome Inhibitors (PIs) (Bortezomib, Carfilzomib, Ixazomib) constitutes the backbone of treatment in MM patients. Cardiotoxic side-effect profile of iMiDs is not well-documented. Although Carfilzomib has been associated with cardiotoxicity, whether its adverse effects also mirror the class-specific cardiotoxic profile of PI remain obscure. Proper assessment of cardiotoxicity due to treatment reagents is necessary for optimal patient management. In this pairwise meta-analysis, we explored direct cardiotoxicity with iMiDs and PIs use in patients with multiple myeloma (MM). Hypothesis: Treatment with iMiDs and PIs in MM patients leads to independent cardiotoxicity that is associated with individual class of drugs. Methods: Published randomized control trials (RCTs) were searched up to May 2021 reporting cardiotoxicity (cumulative reported events of ischemia, arrhythmia, failure, stenosis) in MM patients (newly diagnoses and/or relapsed) treated with iMiD and/or PI. Studies, where iMiD or PI were used atop the chemotherapy vs placebo or no additional drugs (control) in the other arm, were included. The primary outcome was presence of cardiotoxicity after follow-up. Meta-analysis was performed using frequentist’s approach to estimate odds ratio (OR). Results: Eighteen RCTs including 8,479 MM patients were included in this analysis. Eleven studies compared iMiDs and seven studies compared PIs with control. CTACE high-grade (≥ grade 3) cardiotoxic events were increased with iMiDs in comparison to their control counterpart (OR 2.05; 95% CI 1.30-3.26). Cardiotoxicity was also noted more frequently with PI use when compared to the control group (OR 1.47; 95% CI 1.19-1.82). Similar difference was observed between high-grade cardiotoxic complication between these groups. There was no evidence of publication bias among studies. Conclusions: Our results showed iMiDs and PIs are independently associated with cardiotoxicity, which may warrant increased awareness among treating physicians and close monitoring of patients. The adverse cardiac event profile with these drugs require further investigation in future studies.