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. 2021 Apr 1;13(7):1631.
doi: 10.3390/cancers13071631.

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

Anna Astarita  1 , Giulia Mingrone  1 , Lorenzo Airale  1 , Fabrizio Vallelonga  1 , Michele Covella  1 , Cinzia Catarinella  1 , Marco Cesareo  1 , Giulia Bruno  1 , Dario Leone  1 , Carlo Giordana  1 , Giusy Cetani  2 , Marco Salvini  2 , Francesca Gay  2 , Sara Bringhen  2 , Franco Rabbia  1 , Franco Veglio  1 , Alberto Milan  1
Affiliations

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

Anna Astarita et al. Cancers (Basel). .

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.

Keywords: arterial hypertension; cardiovascular adverse events; cardiovascular risk assessment; carfilzomib; echocardiography; global longitudinal strain; multiple myeloma; pulse wave velocity.

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Conflict of interest statement

Alberto Milan received honoraria for advisory board from Amgen and Janssen. Sara Bringhen received honoraria from Bristol-Myers Squibb, Celgene, Amgen and Janssen; advisory boards for Amgen, Karyopharm, Janssen and Celgene; consultancy fees from Takeda and Janssen. Francesca Gay received honoraria from Amgen, Janseen, Celgene, BMS, Takeda, Abbvie; advisory boards for Amgen, Janseen, Celgene, BMS, Takeda, Abbvie; advisory adaptive for Roche Oncopeptides. The other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flow-chart of the Study Protocol.
Figure 2
Figure 2
Probability of incurring CVAEs related to increasing of carfilzomib (CFZ) CVAEs Risk Score. Vertical axis = observed CVAE events (%); Horizontal axis = predicted CFZ CVAE risk (%). The upper points represent patients who experienced CVAEs; the lower points represent patients who did not experienced CVAEs.
Figure 3
Figure 3
Smooth Calibration plot for the validation of CFZ CVAEs Risk Score. Comparison between observed and predicted CVAEs based on bootstrap. The grey line represents the perfect condition in which the observed CVAEs are equal to predicted CVAEs; the black line represents the CVAEs observed in our population.
Figure 4
Figure 4
CFZ CVAEs Risk Score Discrimination plot.
Figure 5
Figure 5
CFZ CVAEs Risk Score Calibration: (a) calibration slope and (b) calibration intercepts.
See this image and copyright information in PMC

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