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. 2022 Apr;40(2):233-242.
doi: 10.1002/hon.2959. Epub 2021 Dec 30.

Cardiotoxicity as an adverse effect of immunomodulatory drugs and proteasome inhibitors in multiple myeloma: A network meta-analysis of randomized clinical trials

Avash Das  1 , Subhajit Dasgupta  1 , Yan Gong  2 , Urvi A Shah  3 , Michael G Fradley  4 , Richard K Cheng  5 , Bhaskar Roy  6 , Avirup Guha  7   8
Affiliations

Cardiotoxicity as an adverse effect of immunomodulatory drugs and proteasome inhibitors in multiple myeloma: A network meta-analysis of randomized clinical trials

Avash Das et al. Hematol Oncol. 2022 Apr.

Abstract

We aim to determine the cumulative and comparative risk of cardiovascular events associated with different Immunomodulatory Drugs (iMiDs) and Proteasome Inhibitor (PIs) in Multiple Myeloma (MM) patients through pairwise and network meta-analysis. Electronic searches were conducted using Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and Clinical Trial Registry (Clinical Trials.gov) up to May 2021. Phase 3 randomized clinical trials (RCTs) reporting cardiotoxicity in MM patients (newly diagnoses and/or relapsed) treated with iMiD and/or PI. Studies, where iMiD or PI was used alongside the chemotherapy versus placebo or no additional drugs (control) in the other arm were included. The primary outcome was the presence of cardiotoxicity after follow-up. Pairwise meta-analysis and network meta-analysis were performed using the frequentist's approach to estimate the odds ratio (OR). Twenty RCTs with 10,373 MM patients were included in this analysis. Eleven studies compared iMiDs with control, seven studies compared PIs with control, and two studies compared bortezomib against carfilzomib. CTACE high-grade (≥grade 3) cardiotoxic events were increased with iMiDs compared to their control counterpart (OR 2.05; 95% CI 1.30-3.26). Similar high-grade cardiotoxicity was also noted more frequently with PI use when compared to the control group (OR 1.67; 95% CI 1.17-2.40). Among the PIs, carfilzomib was associated with a maximum risk of cardiotoxicity (OR 2.68; 95% CI 1.63-4.40). There was no evidence of publication bias among studies. iMiDs and PIs, particularly carfilzomib, appear to be associated with increased risk of high-grade cardiovascular events in MM patients.

Keywords: cardiotoxicity; immunomodulatory drugs; meta-analysis; multiple myeloma; network meta-analysis; proteasome inhibitors.

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Figures

Figure. 1.
Figure. 1.
Study selection flow chart.
Figure 2.
Figure 2.
A. Forest Plot demonstrating the comparative effects of iMiDs in the risk of high-grade cardiotoxicity. B. Forest Plot demonstrating the comparative effects of PIs in the risk of all-grade cardiotoxicity. C. Forest Plot demonstrating the comparative effects of PIs in the risk of high-grade cardiotoxicity.
Figure 2.
Figure 2.
A. Forest Plot demonstrating the comparative effects of iMiDs in the risk of high-grade cardiotoxicity. B. Forest Plot demonstrating the comparative effects of PIs in the risk of all-grade cardiotoxicity. C. Forest Plot demonstrating the comparative effects of PIs in the risk of high-grade cardiotoxicity.
Figure 3.
Figure 3.
A. Network meta-analysis for cardiotoxicity in with individual PI with control. B. Forest Plot demonstrating the comparative effects of the individual PI in the risk of cardiotoxic events. C. League table demonstrating the effects of the individual PI contributing to the risk of cardiotoxicity in MM patients.
See this image and copyright information in PMC

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