The impact of glucagon-like peptide-1 receptor agonists on proteasome inhibitor-associated cardiotoxicity in patients with multiple myeloma.

Abstract

e24008 Background: Patients with multiple myeloma undergoing proteasome inhibitor therapies face an elevated risk of cardiotoxicity. Existing evidence in the non-cancer population indicates that glucagon-like peptide-1 receptor agonists (GLP1a) can mitigate the risk of cardiovascular events. We hypothesize that GLP1a may reduce the risk of cardiotoxicity in patients with multiple myeloma undergoing proteasome inhibitor therapies. Methods: We conducted a retrospective, propensity score-matched cohort study by utilizing the TriNetX Analytics Network database, which contains de-identified data spanning over 250 million patients. We included adult patients with multiple myeloma and type 2 diabetes mellitus who received proteasome inhibitor therapy. We matched patients treated with GLP1a and those treated with Dipeptidyl Peptidase 4 (DPP4i) in a 1:1 ratio based on predetermined clinical variables. The primary outcome included major adverse cardiovascular events, defined as a composite of heart failure and heart failure hospitalization, myocardial infarction, and ischemic stroke. Other outcomes included individual cardiovascular events, atrial fibrillation/flutter, and all-cause mortality within 3 years of proteasome inhibitor therapy. Results: We matched 183 patients on GLP1a to patients on DPP4i. The prevalence of hypertension, ischemic heart disease, and use of proteasome inhibitors was similar between cohorts. In a Cox proportional hazard analysis, patients who received GLP1a had an approximately 50% lower risk of major adverse cardiovascular events (HR, 0.53 [95% CI: 0.29-0.96]) compared to those who received DPP4i. Furthermore, GLP1a was associated with a reduction in heart failure and heart failure hospitalization, ischemic stroke, and all-cause mortality. The risks of myocardial infarction and atrial fibrillation/flutter were comparable between the two cohorts. Conclusions: GLP1a were associated with a reduction in major adverse cardiovascular events and mortality among patients with multiple myeloma and diabetes mellitus receiving proteasome inhibitors. [Table: see text]