In a systematic review and meta-analysis reported in Leukemia & Lymphoma, Shah et al identified the risk of cardiotoxicity among patients, most with multiple myeloma, receiving carfilzomib (Kyprolis) in clinical trials.
The study included data from 4,164 patients who received carfilzomib in 29 eligible phase I/II, phase II, and phase III clinical trials. Of these trials, 27 were in multiple myeloma.
Risk of Cardiotoxicity, Hypertension
The overall estimated cumulative incidence of cardiotoxicity was 8.68% for toxicity of any grade and 4.92% for grade ≥ 3 toxicity among patients receiving carfilzomib. Analysis of data from 2,036 patients enrolled in three phase III trials showed that the use of carfilzomib vs control treatment was associated with an odds ratio of 2.03 (P = .010) for any-grade cardiotoxicity and 2.04 (P = .002) for grade ≥ 3 cardiotoxicity. Odds ratios for hypertension were 2.93 (P < .0001) for any-grade toxicity and 3.33 (P < .0001) for grade ≥ 3 toxicity.
Subgroup analyses showed no significant differences in the incidence of any-grade (P = .38) or high-grade (P = .46) cardiotoxicity between patients with newly diagnosed myeloma and those with relapsed or refractory disease; no significant differences between any-grade (P = .63) or high-grade (P = .86) cardiotoxicity between patients receiving high vs standard doses of carfilzomib; and no significant differences between any-grade (P = .06) or high-grade cardiotoxicity when carfilzomib was used alone vs in combination. However, concomitant use vs nonuse of immunomodulatory agents was associated with an increased incidence of any-grade (15.99% vs 5.94%, P = .006) and high-grade cardiotoxicity (6.45% vs 4.34%, P = .033).
The investigators concluded, “[T]his meta-analysis demonstrates that [carfilzomib] usage does significantly increase the risk of cardiotoxicity and [hypertension]…. [W]hile dose relationship for this [carfilzomib] toxicity cannot be established, concomitant [immunomodulatory agent] use seems to increase the likelihood of cardiotoxicity. Clinicians should be aware of this risk and provide close monitoring to patients receiving this novel agent.”
The authors reported no grant support for the study.
Chintan Shah, MD, of the Division of Hospital Medicine, University of Florida, Gainesville, is the corresponding author for the Leukemia & Lymphoma article.
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