Clinical Implications of Discordant Early Molecular Responses in CML Patients Treated with Imatinib.

A reduction in transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR; 71.5% vs. 16.1%) compared to individuals with levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with values >10% at 3 months but <1% at 6 months fared significantly better than individuals with <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; < 0.001). Likewise, subjects with at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR compared to patients with <10% at 3 months but >1% at 6 months (75% vs. 18.2%; < 0.001). Finally, lower transcripts at diagnosis were associated with values <1% at 6 months ( < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.