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 1 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 2 years of TKI therapy. Patients who achieved a 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%). The achievement of MCyR within the first 2 years of treatment predicted a better OS (HR = 0.43, p = .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 2 years is a reasonable milestone in CML, and these patients can still have good outcomes even when MMR is not achieved.