Second-line bosutinib for chronic phase chronic myeloid leukemia after imatinib: final, 10-year results of a phase I/II study

This is the final ≥10-year report of a phase I/II study and its extension study of second-line bosutinib for chronic phase chronic myeloid leukemia (CP-CML), representing the longest follow-up to date of any tyrosine kinase inhibitor after imatinib failure (n=284). Median (range) follow-up and treatment duration were 53.7 (0.5-171.6) and 25.6 (0.2-170.5) months, respectively. At the start of year 11, 19.4% of patients were receiving bosutinib; 13.4% were receiving bosutinib at study completion. The most common reasons for treatment discontinuation were lack of efficacy (disease progression/unsatisfactory response; 26.8%) and adverse events (26.1%). Cumulative rates of complete cytogenetic response, major molecular response, and MR4 were 49.6%, 42.1%, and 37.1%, respectively. Kaplan-Meier probabilities of maintaining response at year 11 were 58.3%, 56.1%, and 55.7%, respectively. At year 11, cumulative incidence of on-treatment disease progression/death was 24.6%; 15 (5.3%) patients had ontreatment transformations to accelerated/blast phase (one after year 5). The Kaplan-Meier overall survival rate was 70.5%; 55 (19.4%) patients died on study (15 after year 5). At the start of year 11, 29/55 (52.7%) patients still on bosutinib were receiving ≥500 mg once daily. Thirteen patients had adverse events leading to discontinuation in year 6 or later. No new safety signals emerged. After ≥10 years, bosutinib demonstrated durable efficacy and acceptable safety as second-line treatment for CP-CML.