Cardiovascular Events in Multiple Myeloma: A Retrospective Review of the SEER-Medicare Claims Database

Introduction Therapeutic advances in multiple myeloma (MM) therapy have resulted in a rapid improvement in disease-free and overall survival in recent decades. Given the increased lifespan of MM patients (pts), managing comorbidities and preventing adverse treatment effects is integral to improve quality of life and long-term survival. Cardiovascular (CV) events are increasingly recognized as a significant cause of morbidity, mortality, and treatment interruption in MM pts, with current estimates of CV complications ranging broadly from 7.5% in clinical trials to up to 52% in real world retrospective data. There is a critical need to better understand the risk of adverse CV events in the elderly MM population, and identify high risk pts and treatments. Such findings may support the development of predictive models to better guide treatment selection and preventative interventions. Methods Utilizing the SEER-Medicare claims linked database for 2000-2019, pts with newly diagnosed MM with at least 24 months of continuous Medicare Part A & B enrollment and no supplementary insurance were identified. A non-MM cohort representing 5% of the Medicare population with at least one year of Medicare enrollment was selected as a control arm. Demographic characteristics of these cohorts were compared, and pre-existing comorbid conditions, identified by ICD codes for in- or out-patient services, were compared between MM and non-MM pts. Risk of new CV events after MM diagnosis were compared by cox proportional hazards model to non-MM controls. Time zero for controls was randomly assigned using a distribution based on the time between data entry and first MM diagnosis in cases. Cases were excluded if a claim for the event of interest was made prior to MM diagnosis or non-MM entrance date. Models looked at time to first CV event against MM status and included age, sex, hypertension (HTN) and obesity as covariates, with sub analysis for specific CV events. CV-event free survival (CV-EFS) for specified CV events was compared between MM cases and controls. Results A total of 48,797 MM pts and 1,187,698 non-MM controls were identified. Median age was 68 yo (IQR 65-74) for MM and 65 yo (IQR 65-73) for controls. MM pts were more likely to be White (85.8% vs 83.2%) or Black (11.7% vs 8.8%), and male (54.3% vs 42.0%) when compared to non-MM controls, all p<0.001. MM pts were more likely to have baseline anemia (78.3% vs 58.6% of non-MM controls, p<0.001) and chronic kidney disease (39.1% vs 36.8%, p<0.001), with higher rates of HTN (86.4% vs 83.8%, p<0.001). Non-MM controls were more likely to be obese (21.0% vs 13.0% of MM cases, p<0.001), have diabetes (38.0% vs 33.4%, p<0.001), use tobacco (12.4% vs 6.8%, p<0.001), or have alcohol use disorder (5.0% vs 2.1%, p<0.001). Prior to MM diagnosis, 33.1% of MM pts had a documented history of heart failure, 51.1% had a history of ischemic heart disease, and 51.0% had a history of arrhythmia. In a model accounting for sex, obesity, pre-existing HTN and age, MM pts were significantly more likely to develop any new CV event (hazard ratio [HR] 3.7 [95% CI 3.7-3.8], median CV-EFS 8 vs 56 mos), new venous thrombosis (HR 5.4 [95% CI 5.3-5.5], median CV-EFS 143 mos vs not reached), ischemic heart disease (HR 2.3 [95% CI 2.2-2.3], median CV-EFS 67 vs 137 mos), heart failure (HR 3.6 [95% CI 3.5-3.6], median CV-EFS 62 vs 171 months), arrhythmia (HR 3.0 [95% CI 3.0-3.1], median CV-EFS 37 vs 111 mos), and cerebrovascular disease (HR 1.9 [95% CI 1.8-1.9], median CV-EFS 85 vs 134 mos) after diagnosis than non-MM controls, all p<0.001. Obesity, increasing age, and HTN were predictive of increased rates of all examined CV events. Female sex was protective against ischemic heart disease, heart failure, arrhythmia and cerebrovascular disease, with no association between sex and venous thrombosis. Discussion We identified a high rate of new CV events in pts diagnosed with MM. Compared to a similar non-MM population, MM pts had higher rates of venous thrombosis, ischemic heart disease, heart failure, and arrhythmias. Obesity, age, and pre-existing hypertension were predictive of CV events, highlighting the importance of healthcare maintenance in this population. Identification of additional modifiable underlying risk factors and the relationship of MM directed therapies to specific CV events is required to improve pt outcomes.