Reattempt of tyrosine kinase inhibitor discontinuation after maintenance therapy with ponatinib in patients with chronic myeloid leukaemia in the chronic phase: Result of the Japan Adult Leukemia Study Group RE-STOP219 study.

Treatment-free remission (TFR) is now a key goal for chronic-phase chronic myeloid leukaemia (CML-CP) after achievement of a prolonged deep molecular response. About half of these patients can remain in remission without treatment, whereas those who relapse must resume lifelong therapy. This study investigated whether patients who previously failed tyrosine kinase inhibitor discontinuation could achieve TFR after receiving ponatinib as maintenance therapy. Patients who had relapsed after prior tyrosine kinase inhibitor (TKI) discontinuation and subsequently regained molecular response 4.5 (MR4.5; defined as a BCR-ABL1 transcript level ≤0.0032% on the International Scale [IS]) were enrolled, switched to ponatinib (15 mg/day) for 12 months and those who maintained MR4.5 discontinued TKI therapy. The primary end-point was the proportion of patients with TFR at 12 months. Patients losing major molecular response (MMR) resumed ponatinib or their prior TKI. Of 50 enrolled patients, 49 received ponatinib and 41 proceeded to TKI discontinuation. At 12 months, the proportion of patients with TFR was 36.6% (90% confidence interval: 24.1-50.6). Univariate analysis identified favourable factors for TFR: first discontinuation of imatinib, longer initial TKI therapy and longer first TFR duration. In conclusion, ponatinib maintenance followed by a second attempt at TKI discontinuation may facilitate successful TFR in selected CML patients. However, the risk of adverse events highlights the need for careful patient selection.