Multiple Myeloma Patients Undergoing Carfilzomib: Development and Validation of a Risk Score for Cardiovascular Adverse Events Prediction

SIMPLE SUMMARY: Despite the relationship between Carfilzomib (CFZ) therapy in multiple myeloma (MM) and cardiovascular adverse events (CVAEs), no specific validated protocols on cardiovascular risk assessment are available. In this prospective study, we investigated major predictors of CVAEs prior to starting CFZ, applying the European Myeloma Network management protocol (EMN). Five predictors were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ defined a low- and a high-risk group (negative predicting value for the high-risk group of 90%). 62 patients experienced one or more CVAEs: 17 major and 45 hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is required. The EMN protocol and ‘CFZ risk score’ proved to be effective in estimating the baseline risk of CVAEs during CFZ therapy in MM patients, targeting the appropriate follow-up. ABSTRACT: Cardiovascular adverse events (CVAEs) are linked to Carfilzomib (CFZ) therapy in multiple myeloma (MM); however, no validated protocols on cardiovascular risk assessment are available. In this prospective study, the effectiveness of the European Myeloma Network protocol (EMN) in cardiovascular risk assessment was investigated, identifying major predictors of CVAEs. From January 2015 to March 2020, 116 MM patients who had indication for CFZ therapy underwent a baseline evaluation (including blood pressure measurements, echocardiography and arterial stiffness estimation) and were prospectively followed. The median age was 64.53 ± 8.42 years old, 56% male. Five baseline independent predictors of CVAEs were identified: office systolic blood pressure, 24-h blood pressure variability, left ventricular hypertrophy, pulse wave velocity value and global longitudinal strain. The resulting ‘CVAEs risk score’ distinguished a low- and a high-risk group, obtaining a negative predicting value for the high-risk group of 90%. 52 patients (44.9%) experienced one or more CVAEs: 17 (14.7%) had major and 45 (38.7%) had hypertension-related events. In conclusion, CVAEs are frequent and a specific management protocol is crucial. The EMN protocol and the risk score proved to be useful to estimate the baseline risk for CVAEs during CFZ therapy, allowing the identification of higher-risk patients.