BCR::ABL1 kinase domain mutation testing and clinical outcome in a nationwide chronic myeloid leukemia patient population

• Published in: European journal of haematology 2023-12, Vol.111 (6), p.938-945
• Main Authors: Kockerols, Camille, Valk, Peter J. M., Blijlevens, Nicole M. A., Cornelissen, Jan J., Dinmohamed, Avinash G., Geelen, Inge, Hoogendoorn, Mels, Janssen, Jeroen J. W. M., Daenen, Laura G. M., Reijden, Bert A. van der, Westerweel, Peter E.
• Format: Article
• Language: English
• Subjects: Chronic myeloid leukemia; Clinical outcomes; Missense mutation; Mutation; Myeloid leukemia; Patients; Protein-tyrosine kinase
• ISSN: 0902-4441; 1600-0609
• DOI: 10.1111/ejh.14107

ObjectivesAcquired missense mutations in the BCR::ABL1 kinase domain (KD) may cause tyrosine kinase inhibitor (TKI) treatment failure. Based on mutation‐specific in vitro derived IC50‐values, alternative TKI may be selected. We assessed clinical practice of BCR::ABL1 KD mutation testing, clinical response in relation to IC50‐values, and clinical outcome of tested patients.MethodsPatients from six Dutch CML reference centers and a national registry were included once a mutational analysis was performed. Reasons for testing were categorized as suboptimal TKI response, and primary or secondary TKI resistance.ResultsFour hundred twenty analyses were performed in 275 patients. Sixty‐nine patients harbored at least one mutation. Most analyses were performed because of suboptimal TKI response but with low mutation incidence (4%), while most mutations were found in primary and secondary resistant patients (21% and 51%, respectively). Harboring a BCR::ABL1 mutation was associated with inferior overall survival (HR 3.2 [95% CI, 1.7–6.1; p