While clinical trials of the proteasome inhibitor carfilzomib for the treatment of multiple myeloma (MM) showed varying incidence rates of cardiovascular adverse events (AEs), a review of data from the phase I, II, and III trials leading to its approval suggest that the improvements in patient survival are worth the relatively low risk of cardiac failure or hypertension.
“Carfilzomib-based regimens have produced clinically meaningful responses and [have] shown significant improvement in the depth and duration of responses in [this setting] … including a nearly eight-month increase in overall survival,†lead author Ajai Chari, MD, of the Icahn School of Medicine at Mount Sinai in New York, told ASH Clinical News. “While optimization of cardiovascular health is important for all patients, the findings of this study demonstrate the risk of cardiovascular events is far outweighed by the benefit of carfilzomib treatment – as evidenced by improvements in overall survival,†he said.
The pooled analysis, which was published in Blood Advances, included data from 11 clinical trials evaluating carfilzomib in patients with relapsed/ refractory MM that reported incidence of cardiovascular-related AEs, comprising a total of 2,044 patients who received at least one dose of carfilzomib.
The researchers analyzed studies for all grade and grade ≥3 cardiovascularrelated AEs of interest, including cardiac failure, dyspnea, hypertension, and ischemic heart disease. For the purposes of the study, treatment-emergent AEs were defined as events that began on or following the first day of therapy or AEs that presented at baseline and worsened in severity following treatment.
Three trials (ASPIRE, ENDEAVOR, and FOCUS) also included analyses of the cardiac safety profile in 1,012 carfilzomib-treated patients compared with 998 patients in control arms who were treated with either lenalidomide plus dexamethasone, bortezomib plus dexamethasone, or best supportive care, respectively.
In the pooled analysis of all 11 trials, the most frequently reported cardiovascular-related AEs included anygrade incidences of:
- cardiac failure (6.7%)
- hypertension (18.5%)
- dyspnea (31.9%)
Grade ≥3 incidences of cardiac failure, hypertension, and dyspnea were reported in 4.4 percent, 5.9 percent, and 4.5 percent of patients, respectively.
Across the three phase III trials, the incidence of cardiac AEs was numerically higher in carfilzomib than control groups, but, after adjustment for duration of treatment exposure and follow-up, the incidences were similar between the treatment groups (TABLE).