Successful Treatment-Free Remission After Ponatinib Discontinuation in Pretreated Patients with Chronic Myeloid Leukemia in Chronic Phase.

INTRODUCTION

The discontinuation of third-generation BCR::ABL1 tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in chronic phase (CML-CP) is not well understood. We aim to evaluate treatment-free remission in patients with CML-CP who discontinue ponatinib.

METHODS

We retrospectively reviewed 361 patients who attempted TKI discontinuation between November 2005 and February 2024 and identified those receiving ponatinib at the time of discontinuation. Molecular relapse-free survival (MRFS) was calculated from the time of ponatinib discontinuation to the date of loss of major molecular response (MMR) or last follow-up.

RESULTS

Eleven patients discontinued ponatinib. Before ponatinib discontinuation, patients were on TKI therapy for a median of 146.6 months and on ponatinib for a median of 67.5 months. The median number of TKIs prior to starting ponatinib was 2 (range, 1-3). The median durations of sustained MR4 and MR4.5 before ponatinib discontinuation were 32.8 and 29.4 months, respectively. After a median follow-up of 60.3 months, the 60-month MRFS rate was 53%. Five patients lost MMR; their median MR4.5 duration was 5 months before ponatinib discontinuation.

CONCLUSION

Ponatinib discontinuation is feasible in patients with CML-CP failing prior TKIs. Patients who achieve sustained MR4.5 for at least 2 years have the highest likelihood of remaining in treatment-free remission following ponatinib discontinuation.