Carfilzomib therapy clinical benefits, including improved overall survival (OS), outweigh the risk of hypertension and cardiac failure for patients with relapsed and/or refractory multiple myeloma (RRMM), according to a study published in Blood Advances.
Various factors contribute to elevated cardiovascular (CV) risk among patients with MM, such as age, renal failure, hyperviscosity, and treatment-associated cardiotoxicity. Previous studies have shown that carfilzomib significantly improves outcomes in RRMM but may also increase the risk of CV disease; as carfilzomib is becoming more prevalent in the treatment of RRMM, a better understanding of its relationship with CV risk is needed.
For this analysis, researchers evaluated the outcomes of 11 phase 1 to 3 studies, including the phase 3 ASPIRE and ENDEAVOR trials, which investigated the efficacy of carfilzomib among 2044 patients with MM to determine the incidence of CV adverse events (AEs). In addition, a benefit-risk profile for carfilzomib was generated.
Results showed that grade 3 or worse CV adverse events, including hypertension, dyspnea, and cardiac failure, occurred in 5.9%, 4.5%, and 4.4% of study patients, respectively. Although there was an elevated risk of CV adverse events, further analysis showed that the rate of treatment discontinuation or death was low and comparable between the carfilzomib groups and the control groups.
Echocardiography revealed that carfilzomib did not increase cardiac dysfunction compared with the control arms, and also had no effect on cardiac repolarization.
The authors concluded that “the results suggest that the benefit of carfilzomib treatment in reducing disease progression, and even death, outweighs CV risks for most patients. Nonetheless, careful monitoring and management of CV risk factors, including blood pressure and volume status, are recommended for all myeloma patients as good clinical practice.”
Chari A, Stewart AK, Russell SD, et al. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials [published July 10, 2018]. Blood Adv. doi: 10.1182/bloodadvances.2017015545