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. 2025 Jul 15;17(14):2353.
doi: 10.3390/cancers17142353.

Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study

Anna Astarita  1 , Giulia Mingrone  2 , Lorenzo Airale  1 , Anna Colomba  1 , Cinzia Catarinella  1 , Marco Cesareo  1 , Fabrizio Vallelonga  2 , Arianna Paladino  2 , Giulia Bruno  2 , Dario Leone  2 , Francesca Gay  3 , Sara Bringhen  3 , Franco Veglio  1 , Alberto Milan  1   2
Affiliations

Validation of the HFA-ICOS Score for Carfilzomib-Induced Cardiotoxicity in Multiple Myeloma: A Real-Life Perspective Study

Anna Astarita et al. Cancers (Basel). .

Abstract

Background: Despite the inference about the cardiotoxicity induced by Carfilzomib, no validated risk prediction models for adverse cardiovascular events in a real-life population are available.

Objectives: The aim of this study was to evaluate the performance of the risk stratification score for Carfilzomib-induced cardiotoxicity of the Heart Failure Association of the European Society of Cardiology and the International Cardio-Oncology Society (HFA-ICOS) in patients with multiple myeloma (MM).

Methods: This is a prospective, real-world study including MM patients consecutively enrolled prior to starting Carfilzomib, divided into levels of risk according to the HFA-ICOS proforma.

Results: Of 169 patients, 11.8% were classified as 'low risk', 38.5% as 'medium risk', 45.6% as 'high risk' and 4.1% as 'very high risk' at baseline. A total of 89 (52.7%) patients experienced one of the following events: 36 (21.3%) had at least one cardiovascular event and 77 (45.6%) had almost one hypertension-related event. No significant differences were observed for the incidence of any cardiovascular events between the different levels of risk (p > 0.05), even considering the HFA-ICOS score as a continuous variable. The integration of the score with the baseline systolic blood pressure and pulse wave velocity enhanced the accuracy of the score (AUC 0.557 vs. 0.736).

Conclusions: The HFA-ICOS score did not discriminate between patients at low, medium and high risk, showing a limited discriminatory power in predicting the risk of events in our population. The integration of other parameters in the HFA-ICOS score, such as systolic blood pressure and pulse wave velocity, improved the performance of the score.

Keywords: HFA-ICOS score; cardiotoxicity; carfilzomib; multiple myeloma; risk prediction model.

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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; and 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, and Abbvie; and advisory adaptive for Roche Oncopeptides. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of the study protocol.
Figure 2
Figure 2
Incidence of CVAEs by baseline risk groups of HFO-ICOS score.
Figure 3
Figure 3
Accuracy of the HFO-ICOS in predicting CVAEs. (A) ROC curve of HFO-ICOS score (black line) and of HFO-ICOS comprehensive of blood pressure variability > 10 (dark green line), global longitudinal strain (GLS) > −20% (pink line), left ventricular hypertrophy (blue line), pulse wave velocity ≥ 9 m/s, and systolic blood pressure (SBP) ≥ 130 mmHg (green line). (B) ROC curve of HFO-ICOS score (black line), HFO-ICOS score comprehensive of pulse wave velocity ≥ 9 m/s (green line), HFO-ICOS score comprehensive of systolic blood pressure (SBP) ≥ 130 mmHg (red line) and HFO-ICOS score comprehensive of both systolic blood pressure (SBP) and pulse wave velocity ≥ 9 m/s (blue line).
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