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

Chronic myeloid leukemia is a myeloproliferative neoplasm defined by translocation t(9;22)(q34;q11), leading to the BCR::ABL1 fusion gene, which drives unchecked tyrosine kinase activity. Tyrosine kinase inhibitors (TKI) have revolutionised the management of CML offering patients near-normal life expectancy. However, prolonged TKI use poses adverse effects and financial burden. Treatment-free remission (TFR) has emerged as a therapeutic goal, allowing safe discontinuation of TKIs while maintaining remission. However, the cost and logistics of frequent monitoring is yet another problem in resource-limited setting. We evaluated 16 CML patients initiated on TFR at our centre. Out of which eleven patients maintained remission, with a median TKI duration of eight years and a median deep molecular remission of three years, followed over a duration of 66 months. The probability of survival without molecular relapse (SWMR) stabilized at ~ 67% at 60 months. Additionally, on mathematical models of the BCR::ABL1 transcripts after initiation of TFR, distinct patterns in the kinetics in sustained and relapsed patients was identified. Our findings support a modified, risk-adapted TFR monitoring strategy for low- and middle-income countries (LMICs) to enhance surveillance while optimizing resource utilization.