Abstract
Simple SummaryThe management of cardiovascular adverse events in patients with relapsed/refractory multiple myeloma undergoing treatment with carfilzomib can be challenging. Herein, we evaluated the potential cardioprotective effect of daratumumab when administered in combination with carfilzomib and dexamethasone (DaraKd). The study included 25 patients receiving either DaraKd (n = 14) or Kd (n = 11) who were evaluated for echocardiographic changes at the sixth cycle of treatment compared with baseline assessment. DaraKd was associated with preserved post-treatment cardiac systolic function compared with Kd. CD38 inhibition by daratumumab might restore metabolic disequilibrium in the cardiac tissue and prevent cardiac injury. A trend for a lower rate of cardiovascular adverse events among patients receiving DaraKd was also evident, although larger studies are needed to determine the association between echocardiographic and/or biomarker changes with cardiovascular adverse events.Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) (n = 14) or Kd (n = 11). Cardiac ultrasound was performed before treatment initiation and C6D16 or at the time of treatment interruption. Patients were followed for a median of 10 months for CVAEs. The mean (± SD) age was 67.8 ± 7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline demographic characteristics (p > 0.1 for all). In the DaraKd group, we did not observe any significant change in markers of ventricular systolic function. However, these markers deteriorated in the Kd group; left ventricular (LV) ejection fraction, LV global longitudinal strain, tricuspid annular plane systolic excursion and RV free wall longitudinal strain significantly decreased from baseline to second visit (p < 0.05). A significant group interaction (p < 0.05) was observed for the abovementioned changes. CVAEs occurred more frequently in the Kd than the DaraKd group (45% vs. 28.6%). DaraKd was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd. The clinical significance and the underlying mechanisms merit further investigation.
Highlights
Current treatment approaches in multiple myeloma (MM) have significantly enhanced patient outcomes, MM remains an incurable hematological malignancy.Proteasome inhibitors including bortezomib, carfilzomib and ixazomib are among the cornerstones of MM therapeutics [1,2]
In regard to echocardiographic characteristics, left ventricular (LV) mass, left atrial volume index (LAVi) and S wave of LV strain rate were higher whereas LV global longitudinal strain (GLS), peak atrial longitudinal strain (PALS) and right ventricular (RV) free wall longitudinal strain (LS) were lower in the
A predictive model based on baseline office systolic blood pressure, 24 h blood pressure variability, left ventricular hypertrophy, pulse wave velocity and GLS has been recently proposed to predict the risk of cardiovascular adverse events (CVAEs) and stratify the patients in low and high-risk groups [17,18]
Summary
Current treatment approaches in multiple myeloma (MM) have significantly enhanced patient outcomes, MM remains an incurable hematological malignancy. Proteasome inhibitors including bortezomib, carfilzomib and ixazomib are among the cornerstones of MM therapeutics [1,2]. Carfilzomib is a second-generation irreversible proteasome inhibitor that has been shown to improve overall survival (OS) in patients with relapsed and/or refractory multiple myeloma (RRMM) [3]. Carfilzomib has been approved either with dexamethasone (Kd) or with daratumumab and dexamethasonse (DaraKd) or with lenalidomide and dexamethasone (KRd) for patients for RRMM. Carfilzomib may exert cardiovascular adverse events (CVAEs), related mechanisms, prognostic markers and precipitating factors have not been fully characterized [4]. It has been estimated that patients with MM who receive carfilzomib may have an approximately
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