Presence of Myeloid Mutations in Patients with Chronic Myeloid Leukemia Increases Risk of Cardiovascular Event on Tyrosine Kinase Inhibitor Treatment

• Published in: Cancers Vol. 15; no. 13; p. 3384
• Main Authors: Stuckey, Ruth, Segura-Díaz, Adrián, Sáez Perdomo, María Nieves, Pérez Encinas, Manuel Mateo, González San Miguel, Jóse David, Florido, Yanira, Sánchez-Sosa, Santiago, López-Rodríguez, Juan Francisco, Bilbao-Sieyro, Cristina, Gómez-Casares, María Teresa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.06.2023; MDPI
• Subjects: Acute coronary syndromes; Bosutinib; Cardiotoxicity; Cardiovascular diseases; Chronic myeloid leukemia; Diabetes; Diagnosis; Drug therapy; Enzyme inhibitors; Genes; Genetic aspects; Health aspects; Hemopoiesis; Hypertension; Imatinib; Kinases; Leukemia; Malignancy; Medical research; Medicine, Experimental; Mortality; Mutation; Myeloid leukemia; Next-generation sequencing; Nilotinib; Patients; Pharmaceutical industry; Phenols; Remission (Medicine); Risk factors; Software; Spain; Statistical analysis; Survival; Switzerland; Thromboembolism; Thrombosis; Tumors; Tyrosine; Tyrosine kinase inhibitors; Switzerland; Spain; cardiovascular event; next-generation sequencing (NGS); somatic mutation; prognosis; tyrosine kinase inhibitor (TKI); chronic myeloid leukemia (CML); clonal hematopoiesis of indeterminate potential (CHIP)
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15133384

For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or dasatinib. To date, very few studies have evaluated the genetic predisposition associated with CVE development on TKI treatment. In this retrospective study of 102 CML patients, 26 CVEs were reported during an average follow-up of over 10 years. Next-generation sequencing identified pathogenic/likely pathogenic mutations in genes associated with myeloid malignancies in 24.5% of the diagnostic samples analyzed. Patients with a recorded CVE had more myeloid mutations (0.48 vs. 0.14, = 0.019) and were older (65.1 vs. 55.7 years, = 0.016). Age ≥ 60 years and receiving a 2G-TKI in first-line were CVE risk factors. The presence of a pathogenic somatic myeloid mutation was an independent risk factor for CVE on any TKI (HR 2.79, = 0.01), and significantly shortened the CV event-free survival of patients who received first-line imatinib (by 70 months, = 0.011). Indeed, 62% of patients on imatinib with mutations had a CVE vs. the 19% on imatinib with a mutation and no CVE. In conclusion, myeloid mutations detectable at diagnosis increase CVE risk, particularly for patients on imatinib, and might be considered for first-line TKI choice.