Optimizing Treatment-Free Remission (TFR) in Chronic Myeloid Leukemia: Challenges and a Modified Monitoring Strategy...

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR::ABL1 fusion gene.
• Tyrosine kinase inhibitors (TKIs) have significantly improved CML patient outcomes but present challenges like adverse effects and cost.
• Treatment-free remission (TFR) is a goal to safely discontinue TKIs, but monitoring remains a concern, especially in resource-limited settings.

Purpose of the Study:

• To evaluate the feasibility and outcomes of TFR in CML patients.
• To identify distinct BCR::ABL1 transcript kinetics patterns in patients achieving sustained remission versus relapse after TFR.
• To propose a modified, risk-adapted TFR monitoring strategy for low- and middle-income countries (LMICs).

Main Methods:

• Retrospective evaluation of 16 CML patients initiated on TFR.
• Longitudinal follow-up over 66 months to assess remission status and survival without molecular relapse (SWMR).
• Mathematical modeling of BCR::ABL1 transcript kinetics post-TFR initiation.

Main Results:

• Eleven out of 16 patients maintained remission.
• Median TKI duration was 8 years, and median deep molecular remission was 3 years.
• SWMR stabilized at approximately 67% at 60 months, with distinct BCR::ABL1 transcript kinetic patterns observed between sustained and relapsed patients.

Conclusions:

• TFR is a viable strategy for selected CML patients, offering sustained remission for a significant proportion.
• BCR::ABL1 transcript kinetics can potentially predict molecular relapse after TFR.
• A modified, risk-adapted TFR monitoring approach can enhance surveillance and optimize resource use in LMICs.