CML-161: Achieving Treatment-Free Remission in CML Patients Treated With Bosutinib: Data From the ITALY-TFR Registry

Bosutinib is a second-generation tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid leukemia (CML). While treatment-free remission (TFR) is a recognized goal in CML management, limited real-world data exist regarding TFR following bosutinib discontinuation. This sub-analysis from the ongoing ITALY-TFR observational study (NCT04769947) evaluates outcomes in patients who discontinued bosutinib in sustained deep molecular response (DMR). We analyzed data from 20 patients who discontinued bosutinib with at least 1 year of follow-up. Descriptive statistics and Kaplan-Meier survival analyses were applied to assess treatment duration, molecular relapse, and TFR outcomes. Median age at discontinuation was 65 years (interquartile range [IQR], 60.5–71), with 60% male. Bosutinib was used as firstline therapy in 25% of patients (from BELA and BFORE trials), second-line in 30%, and third-line in 45%. The primary reason for switching to bosutinib was intolerance to prior TKIs (65%), with 10% due to resistance. Median total bosutinib treatment duration was 80.5 months (IQR, 63.5–114), and median post-discontinuation follow-up was 4.18 years (IQR, 2.54–5.43). At discontinuation, the median bosutinib dose was 200 mg (range, 100–300 mg), with 40% of patients undergoing prior dose reduction. Discontinuation was due to shared decision-making in 75% of cases and toxicity in 25%. All patients had DMR at discontinuation: 45% MR5, 20% MR4.5, and 35% MR4. Four patients (20%) relapsed molecularly within 6 months and resumed TKI therapy (bosutinib, asciminib, nilotinib, or imatinib). Among these, 75% had received bosutinib as a third-line agent, and only one had achieved MR4.5 prior to stopping. The median treatment duration in relapsed patients was 62 months. No patients experienced disease progression. TFR rates at 12, 24, and 48 months were 80% (95% CI, 60%–93%). Bosutinib discontinuation in pts with sustained DMR appears feasible, with a high TFR rate and no progression observed. Depth of molecular response and treatment duration may influence sustained remission.