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

person Yu-Cheng Chang Department of Medicine, Danbury Hospital, Danbury, CT info_outline Yu-Cheng Chang, Cho Han Chiang, Zhiting Tang, Xin Ya See, Cho Hung Chiang, Kuan-Yu Chi, Yu Chang, Wenli Gao

Authors person Yu-Cheng Chang Department of Medicine, Danbury Hospital, Danbury, CT info_outline Yu-Cheng Chang, Cho Han Chiang, Zhiting Tang, Xin Ya See, Cho Hung Chiang, Kuan-Yu Chi, Yu Chang, Wenli Gao Organizations Department of Medicine, Danbury Hospital, Danbury, CT, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, NY, Unity Hospital, Rochester Regional Health, Rochester, NY, National Taiwan University Hospital, Taipei, Taiwan, Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, National Cheng Kung University College of Medicine, Tainan, Taiwan, Praxair Cancer Center Danbury Hospital, Danbury, CT Abstract Disclosures Research Funding No funding sources reported 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. Outcomes GLP1a DPP4i Hazard Ratio a (95% CI) P-value (Log-rank) No. of at Risk Patients No. of Cases No. of at Risk Patients No. of Cases Major adverse cardiovascular events 109 18 85 28 0.53 (0.29-0.96) 0.032 Heart failure and heart failure hospitalization 117 18 96 33 0.45 (0.26-0.81) 0.006 Myocardial infarction 165 10 166 16 0.43 (0.17-1.09) 0.067 Atrial fibrillation and flutter 136 10 136 15 0.80 (0.36-1.78) 0.58 Ischemic stroke 166 10 160 13 0.16 (0.04-0.72) 0.006 All-cause mortality 183 27 183 62 0.52 (0.33-0.81) 0.004 a After propensity score matching by incorporating variables: age, sex, metastatic disease, proteasome and immunomodulatory therapy, underlying comorbidities, use of cardiovascular and diabetes medications, and hemoglobin A1c.