{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:27:22Z","timestamp":1788280042051,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013International 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\u201314.90; p = 0.009) and elevated NT-proBNP before cycle 2 (&gt;300 pg\/mL; HR 3.13, 95% CI 1.10\u20138.93; p = 0.033) independently predicted CVAEs. A dynamic model incorporating these parameters and adjusting the age threshold to \u226565 years was associated with improved discrimination (AUC 0.72, p = 0.032), model fit (\u0394AIC = \u22124), 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.<\/jats:p>","DOI":"10.3390\/cancers18121924","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T03:01:27Z","timestamp":1781492487000},"page":"1924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Validation and Exploratory Refinement of the HFA-ICOS Score for Cardiovascular Risk in Proteasome Inhibitor-Treated Multiple Myeloma: Single-Center Retrospective Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9595-5982","authenticated-orcid":false,"given":"Eduardo","family":"Pons-Fuster","sequence":"first","affiliation":[{"name":"Clinical Pharmacy and Therapeutics Research Group, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6297-9318","authenticated-orcid":false,"given":"Alejandro","family":"Riquelme-Perez","sequence":"additional","affiliation":[{"name":"Cardiology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav","family":"Shumbar","sequence":"additional","affiliation":[{"name":"Cardiology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia Mar\u00eda","family":"Gonz\u00e1lez-Ponce","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy and Therapeutics Research Group, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Fernandez-Avila","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy and Therapeutics Research Group, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Ram\u00f3n-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Cardiology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Moreno-Belmonte","sequence":"additional","affiliation":[{"name":"Hematology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valent\u00edn","family":"Caba\u00f1as-Perianes","sequence":"additional","affiliation":[{"name":"Hematology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4993-9540","authenticated-orcid":false,"given":"Domingo","family":"Pascual-Figal","sequence":"additional","affiliation":[{"name":"Cardiology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"},{"name":"Medicine Department, University of Murcia, 30003 Madrid, Spain"},{"name":"Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-6665","authenticated-orcid":false,"given":"Mar\u00eda Sacramento","family":"Diaz-Carrasco","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy and Therapeutics Research Group, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Caro-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Cardiology Department, Virgen de la Arrixaca University Clinical Hospital, Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.6004\/jnccn.2023.0061","article-title":"Multiple 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