Pretreatment echocardiographic assessment of left ventricular diastolic function was found to facilitate predicting which patients with multiple myeloma are likely to experience severe carfilzomib-related cardiovascular adverse events (AEs). The findings from this study were published in Blood Advances.
The proteasome inhibitor carfilzomib, approved by the US Food and Drug Administration (FDA) as a single agent or in combination with dexamethasone or dexamethasone and lenalidomide for pretreated relapsed/refractory multiple myeloma (R/R MM), has been associated with development of severe cardiovascular AEs in some patients; however, established predictors for these effects are lacking. The aim of this study was to determine whether baseline assessment of left ventricular diastolic function using noninvasive echocardiography could predict cardiovascular adverse effects with subsequent carfilzomib-based therapy.
This retrospective study was conducted at a single institution and involved a cohort of 72 consecutive Asian patients with relapsed/refractory multiple myeloma who received carfilzomib-based therapy between August 2016 and September 2018. All patients had been assessed for left-ventricular diastolic dysfunction (LVDD) by echocardiography within 2 weeks of initiating treatment with carfilzomib. On the basis of the echocardiographic assessment, patients were classified as having a negative, intermediate, or definite likelihood of developing LVDD.
Baseline patient characteristics included a median age of 70 years, a median of 3 prior chemotherapy regimens, and a median of 6 cycles of carfilzomib. Only 1 patient had previously received anthracycline-based therapy, and none had undergone a reduction in carfilzomib dose prior to manifestation of a cardiovascular AE. Pretreatment echocardiography classified 34.7% (n=25) of patients with intermediate LVDD and 27.8% (n=20) of patients with definite LVDD.
Severe cardiovascular adverse events (grade 3 or higher) were observed in 12 patients (16.7%), and all occurred within the first 3 months of carfilzomib treatment. These included acute heart failure (n=7), hypertension (n=6), reduction in left ventricular ejection fraction (n=4), acute coronary syndrome (n=2), and QT prolongation (n=2). Three patients experienced grade 5 cardiovascular adverse events.
A key finding from this study was that at least 1 severe cardiovascular adverse event occurred in 9 patients whose likelihood of developing LVDD was classified as definite, 2 classified as intermediate, and 1 classified as negative. Although the risk of a cardiovascular adverse event was also significantly increased in patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or higher (odds ratio [OR], 5.98; P =.008) and more than 3 prior treatment regimens (OR, 5.06; P =.016), an LVDD classification of definite was associated with an OR of 13.4 (P <.001).
Based on these findings, the authors suggest that assessing left ventricular diastolic function prior to carfilzomib treatment allows clinicians to individualize chemotherapy, monitoring, and prophylaxis strategies based on patients’ risk of cardiovascular adverse events.
Abe Y, Kobayashi T, Narita K, Kobayashi H, et al. Left ventricular diastolic function as a possible predictor of severe carfilzomib-induced cardiovascular events. Blood Adv. 2019;3(11):1725-1728.