Cardiovascular adverse events may be common in patients with multiple myeloma (MM) treated with proteasome inhibitors, according to results from a prospective, observational study published in the Journal of Clinical Oncology. Cardiovascular adverse events are particularly common with carfilzomib therapy within the first 3 months of treatment.
Researchers assessed the risk factors and outcomes in 95 patients with relapsed MM receiving carfilzomib- (65 patients) or bortezomib-based (30 patients) therapy. Median follow-up was 25 months.
A total of 64 cardiovascular adverse events occurred, 55% of which were grade 3 or greater. Although cardiovascular adverse events occurred in 51% of patients treated with carfilzomib, they occurred in just 17% of patients treated with bortezomib (P =.002).
Cardiovascular adverse events were particularly common in the first 3 months. Median time to first cardiovascular adverse event was 31 days, and 86% of cardiovascular adverse events occurred within the first 3 months of starting therapy.
Patients in the carfilzomib group who had elevated baseline levels of the cardiac biomarkers brain natriuretic peptide (BNP; > 100 pg/mL) and N-terminal proBNP (> 125 pg/mL) experienced an increased risk of developing a cardiovascular adverse event (odds ratio [OR], 10.8; P <.001). Additionally, increased natriuretic peptides occurring in the middle of the first cycle of the carfilzomib regimen were correlated with a significantly higher risk for cardiovascular adverse events (OR, 36.0; P <.001).
“[A] majority of [cardiovascular adverse events] were transient, and natriuretic peptides returned to near-baseline values [at] a median of 24.5 days from peak,” the researchers wrote.
Patients who experienced a cardiovascular adverse events had worse progression-free survival (log-rank P =.01) and overall survival (log-rank P <.001). In patients for whom proteasome inhibitor therapy was held, 89% were able to reinitiate therapy, though 41% needed chemotherapy modifications.
Of note, as this was an observational study, 74% of patients in the carfilzomib arm were male, but only 50% of patients in the bortezomib arm were male (P =.02). Patients in the carfilzomib arm also took longer to enroll (37.4 months vs 18.6 months; P =.03), had higher use of tobacco (43% vs 13%; P =.004), and had more prior lines of chemotherapy prior to enrollment (2 lines vs 1 line; P =.003).
1. Cornell RF, Ky B, Weiss BM, et al. Prospective study of cardiac events during proteasome inhibitor therapy for relapsed multiple myeloma [published online June 12, 2019]. J Clin Oncol. doi:10.1200/jco.19.00231