Cardiovascular risk assessment in multiple myeloma patients undergoing carfilzomib therapy: a new risk prediction model for cardiovascular adverse events

Abstract

Funding Acknowledgements Type of funding sources: None. Background Cardiovascular adverse events (CVAEs) are closely related to Carfilzomib (CFZ) therapy in multiple myeloma (MM), but validated management protocols are lacking. Moreover, the incidence, nature and risk factors for each type of CVAEs are incompletely characterized. Purpose To assess if the European Myeloma Network Guidelines (EMN) protocol is effective on cardiovascular risk assessment before CFZ starting. A prediction model for estimating the probability of CVAEs was developed and validated. Major and hypertensive-related CVAEs were investigated. Methods A perspective study on 116 MM patients scheduled for CFZ therapy was conducted from 2015 to 2020. Before CFZ starting, a baseline evaluation, according to the EMN protocol, was performed; during the follow-up, the incidence of CVAEs was detected. The potential risk factors for CVAEs were identified and a risk score was developed. Results The rate of all-grade CVAEs was 44.8% (24.1% CTCAE≥3): 14.7% experienced major CVEAs (41.2% arrhythmias, 23.5% acute ischemic cardiopathy as most represented) and 30.2% hypertensive-related CVAEs. At baseline, five independent predictors for all-CVAEs were identified: office systolic blood pressure (p = 0.003), 24-hours blood pressure variability (p = 0.004), left ventricular mass (p = 0.015), pulse wave velocity (p = 0.002) and global longitudinal strain (p = 0.033). The resulting CVAEs risk score allows to define the low- and high-risk groups, obtaining a sensibility of 94% in predicting CVAEs (AUC 0.76). Conclusions The comprehensive evaluation of EMN Guidelines is effective in CVAEs prediction. The use of CVAEs risk score will identify the higher risk patients, targeting appropriate follow-ups and organizing effective risk mitigation strategies. Instrumental determinants with CVAEs Parameters No CVAEs N = 64 [N (%)] CVAEs N = 52[N (%)] P value LV mass/BSA 85.30 ± 19.72 95.14 ± 21.75 0.013 LV hypertrophy [> = 95 g/m2 F > = 115 g/m2 M] 8 (12.7) 16 (30.8) 0.018 LV dilation 5 (9.3) 4 (8.9) 0.949 LV EF % 63.03 ± 6.56 61.96 ± 7.13 0.414 GLS % -22.37 ± 2.56 -21.3 ± 2.46 0.029 LV Diastolic dysfunction 1 (1.6) 0(0) 0.362 PWV 7.41 ± 1.63 8.55 ± 1.855 0.002 PWV ³ 8.75 m/s 10 (17.5) 24 (54.2) 0.000 SBP Systolic Blood Pressure; ABPM Ambulatory Blood Pressure Monitoring; BPV Blood Pressure Variability; BSA Body Surface Area; SD Standard Deviation; EF Ejection Fraction; GLS Global Longitudinal Strain; LV Left Ventricle; PWV Pulse Wave Velocity Abstract Figure. CVAEs risk score

Metabolomic signatures of carfilzomib‐related cardiotoxicity in patients with multiple myeloma

“…Correlation between these parameters with metabolomics should be a focus of future research. 48,49 Finally, before we can translate this risk stratification tool into the clinical setting, we need to validate the metabolites MRS in an independent study. Clinical decision support could then be developed and implemented into the electronic health records to assist clinicians in identifying high-risk MM patients before carfilzomib treatment so that alternative treatment could be considered.…”

“…Full echocardiographic data including diastolic parameters recently implicated in carfilzomib‐CVAE are not available. Correlation between these parameters with metabolomics should be a focus of future research 48,49 . Finally, before we can translate this risk stratification tool into the clinical setting, we need to validate the metabolites MRS in an independent study.…”