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.