Early Molecular Response to Imatinib First-Line Therapy and Predictive Factors of Poor Outcomes for Chronic Myeloid...

Objective: The present study aimed to evaluate for the first time, the early molecular response (EMR) to imatinib at 3 months for patients with chronic myeloid leukemia and to determine the predictive factors that influence poor outcome and response. Methods: 60 newly diagnosed CML patients were enrolled from May 2018 to June 2023. They received imatinib and prospectively underwent a molecular evaluation. Their EMR was assessed using a RT-qPCR method and expressed as the BCR::ABL1 IS transcript level at 3 months. Potential factors impacting the EMR were identified using the Cox proportional hazard regression models. The effects of an EMR on the cumulative incidence of a deep molecular response (DMR) were also evaluated. Results: Out of the 60 CML patients recruited, 29 (48%) achieved an optimal response with TKI therapy after 3 months. The cumulative rate of molecular response was 16 (36%) for a major molecular response (MMR), 10 (23%) for MR4, 8 (18%) for MR4.5, and 6 (14%) for MR5, while 4 (9%) showed indetectable transcript. In addition, as 26 (90%) of patients with optimal response at 3 months showed a DMR, we determined that an optimal response to TKI at 3 months was significantly correlated with a DMR. We also identified through multivariate analysis that seven independent risk factors significantly influenced an EMR to TKI. These factors included male, late diagnosis, advanced performance status, the presence of splenomegaly, high-ELTS risk groups, a BCR::ABL1 domain mutation, and complete hematologic response after more than 30 days. Conclusion: Our study demonstrates that an EMR at 3 months has a predictive value for a DMR. In addition, a MMR and a DMR can be predicted using a combination of parameters that either have a significant impact on the optimal response, or that can serve as prognostic indicators for molecular response, especially in low-income countries, where molecular assessment and monitoring are not available or possible.