Introduction:
Multiple myeloma is characterized by neoplastic proliferation of plasma cells that produce monoclonal immunoglobulins. Proliferation of cells in the bone marrow often causes osteolytic lesions, osteopenia and/or pathologic fractures, subsequent hypercalcemia stemming from bone destruction and anemia mainly due to bone marrow replacement1. There is also observed renal dysfunction due to accumulation and precipitation of light chains which form casts in distal renal tubules 2. It is estimated that 35000 new cases are diagnosed annually, accounting for nearly 2% of all new cancer diagnoses3. Age-adjusted death rates have not changed significantly over 2009–2018 and have remained at around 3.1 per 100,000 population3.
While the initial therapy before newer therapeutic advances has classically consisted of VRd (bortezomib + lenalinomide + dexamethasone) and/or stem cell transplant with bortezomib/lenalinomide maintenance4, we have had newer approvals for treatment of multiple myeloma which have received at least one previous regimen. Between 2015-2016, the FDA approved 4 new drugs – elotuzumab (activates NK cells)5, ixazomib (proteosome inhibitor)6, daratumumab (targeting CD38)7, panobinostat(histone deacetylase inhibitor)8 and more recently belantamab and selinexor in 20209,10. Clinical Daratumumab is frequently used in first line regimens along with VRd as D-VRd4.
While the usage of these drugs has increased in the recent years, there is little published evidence about their cardiovascular adverse effect profile. One of the largest trials, the CASTOR trial that included 283 and 286 patients in the VRd and D-VRd arms respectively reported few cardiovascular side effects; two patients with atrial fibrillation in both arms, one patient with acute coronary syndrome among others in the D-VRd arm that could not reach statistical significance given low sample size11. However, a comprehensive study investigating the cardiovascular profile of the new antimyeloma therapy is lacking. Therefore, we sought to utilize FAERS database to analyze the reported cardiovascular adverse events of the newly approved multiple myeloma therapies since 2015.