Efficacy and Safety of Bosutinib By Age and Charlson Comorbidity Index in Previously Treated Patients with Chronic Myeloid Leukemia: Results from the Phase 4 Byond Study

Introduction: Bosutinib is approved for use in patients with Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant or intolerant to prior therapy and in patients with newly diagnosed Ph+ chronic phase (CP) CML.

Methods: In the ongoing BYOND trial (NCT02228382), patients with pretreated CML received bosutinib at a starting dose of 500 mg/day. Here we report efficacy and safety of bosutinib in 156 patients with Ph+ CP CML by i.) age: ≥65 (n=61) vs <65 years (n=95) and ≥75 (n=28) vs <75 years (n=128), and ii.) comorbidities. Charlson Comorbidity Index scores (without the age component; mCCI) were derived from baseline data and patients grouped by mCCI score 2 (n=100), 3 (n=27), and ≥4 (n=29). Data are reported at ≥1 year after the last enrolled patients, and median follow-up time was 30.4 months; approximately 85% of patients had a minimum follow-up of 2 years.

Results: Median duration of treatment was 23 vs 24 months for patients ≥65 vs <65 years as well as for patients ≥75 vs <75 years; respective median dose intensity was 304 vs 343 mg/day and 265 vs 340 mg/day. Cumulative response rates according to age group are shown in the table. Grade 3/4 treatment-emergent adverse event (TEAE) rates were 82% vs 68% for patients ≥65 vs <65 years, and 89% vs 70% for patients ≥75 vs <75 years. Bosutinib was permanently discontinued by 56% vs 36% of patients ≥65 vs <65 years, and 61% vs 40% of patients ≥75 vs <75 years, most commonly due to adverse events (AEs; 33% vs 20% and 36% vs 23%, respectively). Deaths occurred in 10 vs 0 patients ≥65 vs <65 years, and 4 vs 6 patients ≥75 vs <75 years.

Median treatment duration for patients with mCCI 2, 3, and ≥4 was 24, 24 and 18 months; respective median dose intensity was 344, 299 and 304 mg/day. Cumulative response rates across mCCI are shown in the table. Grade 3/4 TEAE rates were 73%, 70%, and 79% for patients with mCCI 2, 3, and ≥4. Bosutinib was permanently discontinued by 38%, 44% and 62% of patients with mCCI 2, 3, and ≥4, most commonly due to AEs (22%, 26%, and 35%, respectively). Deaths occurred in 4, 3, and 3 patients with mCCI 2, 3, and ≥4.

Conclusions: Bosutinib efficacy was demonstrated across age groups and mCCI scores. Older patients (≥65 or ≥75 years) and those with high comorbidity burden (mCCI ≥4) showed a trend towards higher rates of TEAEs and discontinuations due to AEs and may require more careful monitoring.