Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia

BACKGROUND Several studies have demonstrated that approximately one‐half of patients with chronic myeloid leukemia (CML) who receive treatment with tyrosine kinase inhibitors (TKIs) and achieve and maintain a deep molecular response (DMR) are able to successfully discontinue therapy. In patients who have a molecular relapse, a DMR is rapidly regained upon treatment re‐initiation. METHODS The authors report the results from RE‐STIM, a French observational, multicenter study that evaluated treatment‐free remission (TFR) in 70 patients who re‐attempted TKI discontinuation after a first unsuccessful attempt. After the second TKI discontinuation attempt, the trigger for treatment re‐introduction was the loss of a major molecular response in all patients. RESULTS The median follow‐up was 38.3 months (range, 4.7‐117 months), and 45 patients (64.3%) lost a major molecular response after a median time off therapy of 5.3 months (range, 2‐42 months). TFR rates at 12, 24, and 36 months were 48% (95% confidence interval [CI], 37.6%‐61.5%), 42% (95% CI, 31.5%‐55.4%), and 35% (95% CI, 24.4%‐49.4%), respectively. No progression toward advanced‐phase CML occurred, and no efficacy issue was observed upon TKI re‐introduction. In univariate analysis, the speed of molecular relapse after the first TKI discontinuation attempt was the only factor significantly associated with outcome. The TFR rate at 24 months was 72% (95% CI, 48.8%‐100%) in patients who remained in DMR within the first 3 months after the first TKI discontinuation and 36% (95% CI, 25.8%‐51.3%) for others. CONCLUSIONS This study is the first to demonstrate that a second TKI discontinuation attempt is safe and that a first failed attempt at discontinuing TKI does not preclude a second successful attempt. Cancer 2017;123:4403‐10. © 2017 American Cancer Society. RE‐STIM is a French observational, multicenter study evaluating treatment‐free remission in 70 patients who re‐attempt tyrosine kinase inhibitor discontinuation after a first unsuccessful attempt, with the loss of a major molecular response used as a trigger for therapy re‐introduction. No safety issue is reported, and the treatment‐free remission rate at 36 months is 34% (95% confidence interval, 23.6%‐49%), demonstrating that a first failed attempt at discontinuing tyrosine kinase inhibitor does not preclude a second successful attempt.