Cardiovascular adverse events in multiple myeloma patients: A comparative study analysis of daratumumab vs. lenalidomide.

e19550 Background: Advances in treatment strategies in multiple myeloma (MM) have significantly improved life expectancy and progression-free survival. However, many drug classes are associated with substantial cardiovascular (CV) adverse effects, impacting long term outcomes and quality of life. Although Daratumumab and Lenalidomide are widely used in MM treatment, limited data on head-to-head comparisons of their CV outcomes. The study aims to address this gap by evaluating and comparing the CV safety profiles of these drugs in a real-world setting. Methods: A retrospective, propensity score-matched study was conducted using the TriNetX database. Patients with MM, diagnosed between 2019 and 2024 and treated with either Daratumumab or Lenalidomide were included. The primary outcome was major CV adverse effects, including heart failure (HF), myocarditis, myocardial infarction (MI), arrhythmias, pulmonary embolism (PE), deep vein thrombosis (DVT) and myocarditis. Propensity score matching accounted for demographics, comorbidities, and disease status. Hazard-ratio (HR) and risk assessments were performed for individual CV outcomes. Results: A total of 804 patients were included in each group after matching. At 5 years, new-onset arrhythmias occurred in 358 patients in the Daratumumab group compared to 275 patients in the Lenalidomide group (RR 1.3 [95% CI: 1.15–1.47]; p<0.001; HR 1.27, p<0.05). DVT occurred in 89 patients in Daratumumab when compared to 120 patients in the Lenalidomide group (RR 0.742 [95% CI: 0.57 – 0.95]; p<0.02; HR 0.70, p=0.21). Conclusions: Daratumumab is associated with a 30% higher risk of new-onset arrhythmias compared to Lenalidomide, highlighting the need for close monitoring in patients receiving Daratumumab, particularly those with pre-existing arrhythmias or risk factors. Conversely, Lenalidomide is associated with a 25.8% increased risk of DVT when compared to Daratumumab, emphasizing the importance of thromboprophylaxis. The risks of HF, myocardial infarction, myocarditis, PE are similar between both groups. These findings underscore the need for personalized, patient-centric treatment decisions in the management of MM. Cardiovascular adverse events in Daratumumab v/s Lenalidomide:. CVAE Daratumumab(n) Lenalidomide (n) RR [95% CI] p-value HR(p-value) New-onset arrhythmias 358 275 1.3[1.15-1.47] <0.05 1.27 (<0.05) DVT 89 120 0.74[0.57-0.95] <0.05 0.70 (0.21) MI 106 105 1.01[0.78-1.29] 0.94 0.97 (0.67) HF 363 367 0.98[0.88-1.10] 0.84 0.94 (0.53) PE 98 112 0.87[0.67-1.12] 0.3 0.84 (0.90) Myocarditis 10 10 1.0[0.41-2.38] 1.0 1.86 (0.80)