Analysis of early molecular response at 3 months in predicting overall response in newly diagnosed patients with chronic myeloid leukemia on imatinib

Objectives: This study aimed to study the correlation between Breakpoint Cluster Region- ABelson Leukemia virus 1 transcript levels at 3 months with the treatment responses at 6 and 12 months in patients on imatinib. Around 30% of patients with chronic myeloid leukemia (CML) might have treatment failure with the first-line tyrosine kinase inhibitors (TKI). Patients with a “warning response” at 3 months can continue therapy with the same TKI while monitoring for disease progression. However, newer pieces of evidence suggest that patients who fail treatment with imatinib do have suboptimal responses in the early time points, and hence, 1st 3-month assessment might be a useful indicator for future treatment failure. Material and Methods: It is a single-center prospective observational study involving 60 treatment-naive consecutive patients with CML-chronic phase who attended Hematology Outpatient Department at IHTM, Kolkata. Treatment responses were assessed by cytogenetics and BCR-ABL1 transcript levels by real-time quantitative polymerase chain reaction at 3 monthly time points. Results: About 51% and 70.2% of the study participants achieved complete cytogenetic response at 6 and 12 months, respectively. About 74% of the participants had achieved early molecular response (EMR) at 3 months. The failure rates of cytogenetic responses were 13% and 20% at 6 and 12 months, respectively. Patients who failed to achieve EMR at 3 months had higher failure rates at 6 months. The major, warning and failure of molecular responses at 6 and 12 months were found to be 15%, 25%, and 9%, and 34%, 39%, and 27%, respectively. The analyses showed that patients who failed to achieve EMR at 3 months are also more likely to have the failure of molecular response at 12 months, with a statistical significance of P < 0.01. Failure of EMR at 3 months also correlated with failure of overall responses (both cytogenetic and molecular at 12 months) with a statistical significance of P = 0.006. When followed up, there was a progression of disease in three including a death in the suboptimal response group. Conclusion: Our patients had inferior treatment responses to imatinib than that observed in the previous studies. The majority have baseline fibrosis of the marrow and splenomegaly at presentation which might contribute to adverse outcomes. The molecular response at 3 months was found to be a consistent and powerful indicator of treatment responses at later time points.