Chronic Myeloid Leukemia Without Major Molecular Response After 2 Years of Treatment with Tyrosine Kinase Inhibitor.

Achieving major molecular response (MMR) with BCR::ABL1 tyrosine kinase inhibitors (TKIs) is associated with lower chances of progression to advanced phase disease and higher chances of treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML). Failure to achieve this molecular milestone after one year has been highlighted as "suboptimal" or "warning" sign of treatment failure in CML guidelines and recommendations and implied to predict a poor long-term outcome. In this analysis, we report the long-term outcome of 131 patients who did not achieve MMR within the first two years of TKI therapy. Patients who achieved major cytogenetic response (MCyR; roughly equivalent to BCR::ABL1 transcript levels on the International Scale [IS] <10%) had good long-term overall survival (OS) (10-year OS of 88%) and CML-related overall survival (CML-OS) (10-year CML-OS of 95%). Achievement of MCyR within the first two years of treatment predicted for better OS (HR=0.43, P=0.03). The value of MMR was even less pronounced among patients aged 60 years or older at diagnosis, in whom mortality was primarily due to comorbidities unrelated to CML (10-year OS of 55% vs 10-year CML-OS of 100%). In conclusion, achievement of MCyR within two years is a reasonable milestone in CML, and these patients can still have good outcomes even when MMR is not achieved. This article is protected by copyright. All rights reserved.