Cardiovascular complications of modern multiple myeloma therapy: A pharmacovigilance study

Abstract

Aims Multiple myeloma accounts for over 10–15% of haematological malignancies. Continued molecular advances have resulted in the development of new drugs for treatment of multiple myeloma. Four drugs were approved by the Food and Drug Administration (FDA) in 2015, but their safety is not well defined. The aim of this study is to delineate the cardiovascular adverse events of these drugs. Methods We reviewed the adverse cardiac events of newly approved FDA drugs since 2015 using the US FDA Adverse Events Reporting System (FAERS) database. We calculated the reporting odds ratio (ROR) with 95% confidence interval (CIs) for the drugs that have the highest incidence of cardiovascular adverse events. Results Among the medications that have approved for multiple myeloma between 2015 and 2020, 4 novel drugs showed the highest incidence of cardiotoxicity. ROR (95% CI) for atrial fibrillation due to elotuzumab, ixazomib, daratumumab and panobinostat compared to other FAERS drugs was 5.8 (4.4–7.7), 1.9 (1.5–2.3), 4.8 (4.2–5.6) and 5.7 (4.1–8.1), respectively. The ROR (95% CI) for cardiac failure was 8.2 (6.4–10.5), 4.7 (4.1–5.4), 5.8 (4.9–6.7) and 5.6 (3.8–8.1) and ROR (95% CI) for coronary disease was 2.7 (1.9–3.9), 2.7 (2.3–3.2), 2.3 (1.9–2.8) and 4.6 (3.2–6.6) due to elotuzumab, ixazomib, daratumumab and panobinostat compared to all other drugs in FAERS. Conclusion Our results demonstrated that certain newly approved antimyeloma therapies are significantly associated with previously unknown cardiotoxicity. These results warrant further studies and highlight the importance of considering the cardiac history of patients with multiple myeloma when utilizing these novel agents.

Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database

“…In addition, we calculated the time-to-onset of gastrointestinal AEs and the proportion of AE outcomes that were caused by different GLP-1 RAs. The calculation method of time-to-onset is the interval between the start time of GLP-1 RAs’ utilization and the time of AE occurrence ( 19 ). Reports with date errors (drug use time later than event occurrence time) and missing date data were excluded.…”

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

“…Lenalidomide in combination with dexamethasone has also been associated with an increased risk of myocardial infarction (MI) when compared to dexamethasone alone (1.98% versus 0.57%), as well as that of stroke (3.4% versus 1.7%) as reported in 2 phase III studies in patients with relapsed disease [ 20 ]. Data regarding adverse events (AEs) with Thalidomide compared to all other agents from the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database have shown an OR of 2.5 (2.2544–2.7749; p < 0.0001) for AF, 2.77 (2.5856–2.9739; p < 0.0001) for cardiac failure, and 1.5 (1.4081–1.6540; p < 0.0001) for CAD [ 21 ]. For Lenalidomide, the ORs were 2.8 (2.7060–2.9229; p < 0.0001), 1.68 (1.6315–1.7480; p < 0.0001) and 1.08 (1.0508–1.1306; p < 0.0001) respectively [ 21 ].…”

“…Data regarding adverse events (AEs) with Thalidomide compared to all other agents from the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database have shown an OR of 2.5 (2.2544–2.7749; p < 0.0001) for AF, 2.77 (2.5856–2.9739; p < 0.0001) for cardiac failure, and 1.5 (1.4081–1.6540; p < 0.0001) for CAD [ 21 ]. For Lenalidomide, the ORs were 2.8 (2.7060–2.9229; p < 0.0001), 1.68 (1.6315–1.7480; p < 0.0001) and 1.08 (1.0508–1.1306; p < 0.0001) respectively [ 21 ]. In addition, there have been two case reports of myocarditis possibly related to lenalidomide [ 22 , 23 ], although causal effect is yet to be proven.…”

“…Similarly, the KEYNOTE-183 randomised, open-label, phase 3 trial performed at 97 medical centers across 11 countries in MM patients previously treated with at least two lines of therapy, which compared pomalidomide combined with dexamethasone with or without the addition of pembrolizumab, reported death related to MI, cardiac failure, pericardial hemorrhage and myocarditis, the latter being possibly related to pembrolizumab given the well-known safety profile of PD-1 inhibitors [ 24 ]. Based on the FAERS database, the OR of AF with pomalidomide was 3.2 (3.0329–3.5223; p < 0.0001), that of cardiac failure was 1.3 (1.2001–1.4152; p < 0.0001) and that of CAD was 0.65 (0.5950–0.7258; p < 0.0001) [ 21 ]. Conversely, novel agents such as Iberdomide, a cereblon E3 ligase modulator (CELMoD) has not yet been associated with significantly increased risk for cardiac toxicities.…”

LncRNA RP11-1100L3.8 Involves in the Pathogenesis of Multiple Myeloma by Regulating NR4A1

“…Multiple myeloma (MM) is a group of incurable malignant plasma cell diseases, manifested by abnormal bone marrow plasma cells proliferation with a complex array of clinical characterizations containing compromised renal function, lytic bone lesions, anemia, hypercalcemia, and immune dysfunction. It is the second most common hematological malignancies, with approximately 176,400 new diagnosed patients and 11,7000 death cases worldwide only in 2020 [1][2][3]. Its traditional therapeutic method is chemotherapy or chemotherapy combined with stem cell transplantation.…”