Patient-specific molecular response dynamics can predict the possibility of relapse during the second treatment-free...

In chronic myelogenous leukemia (CML), treatment-free remission (TFR) is defined as maintaining a major molecular response (MMR) without a tyrosine kinase inhibitor (TKI), such as imatinib (IM). Several studies have investigated the safety of the first TFR (TFR₁) attempt and suggested recommendation guidelines for such an attempt. However, the plausibility and predictive factors for a second TFR (TFR₂) have yet to be reported. The present study included 21 patients in chronic myeloid leukemia who participated in twice repeated treatment stop attempts. We develop a mathematical model to analyze and explain the outcomes of TFR₂. Our mathematical model framework can explain patient-specific molecular response dynamics. Fitting the model to longitudinal BCR-ABL1 transcripts from the patients generated patient-specific parameters. Binary tree decision analyses of the model parameters suggested a model based predictive binary classification factor that separated patients into low- and high-risk groups of TFR₂ attempts with an overall accuracy of 76.2% (sensitivity of 81.1% and specificity of 69.9%). The low-risk group maintained a median TFR₂ of 28.2 months, while the high-risk group relapsed at a median time of 3.25 months. Further, our model predicted a patient-specific optimal IM treatment duration before the second IM stop that could achieve the desired TFR₂ (e.g., 5 years).