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.