Validation and Exploratory Refinement of the HFA-ICOS Score for Cardiovascular Risk in Proteasome Inhibitor-Treated Multiple Myeloma: Single-Center Retrospective Study.

Background

Proteasome inhibitors (PIs) are integral in multiple myeloma (MM) treatment but carry a substantial risk of cardiovascular adverse events (CVAEs). The Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) risk score was designed to identify patients at risk of cardiotoxicity, but its performance in MM remains uncertain.

Methods

We retrospectively evaluated 98 patients with MM or primary amyloidosis treated with PIs between 2019 and 2024 to externally validate and refine this score.

Results

CVAEs occurred in 22 patients (22.5%), predominantly heart failure. The original HFA-ICOS model demonstrated modest predictive accuracy (AUC 0.66) and sensitivity (50%), with frequent risk overclassification. Carfilzomib exposure (HR 4.68, 95% CI 1.47-14.90; p = 0.009) and elevated NT-proBNP before cycle 2 (>300 pg/mL; HR 3.13, 95% CI 1.10-8.93; p = 0.033) independently predicted CVAEs. A dynamic model incorporating these parameters and adjusting the age threshold to ≥65 years was associated with improved discrimination (AUC 0.72, p = 0.032), model fit (ΔAIC = -4), and CVAE-free survival stratification (p = 0.026), achieving 90.9% sensitivity.

Conclusions

These findings indicate that the original HFA-ICOS score has limited prognostic value in PI-treated MM patients. Incorporating early NT-proBNP monitoring, carfilzomib exposure, and refined age categorization may improve risk prediction and support more personalized cardiovascular surveillance strategies in cardio-oncology. However, this refined dynamic model should be regarded as exploratory and requires validation in larger independent cohorts before it can be considered for clinical application.