Efficacy and safety of the second-generation tyrosine kinase inhibitor bosutinib in the treatment of chronic myeloid leukemia in the chronic phase

Introduction. ABL tyrosine kinase inhibitors (TKIs) have significantly improved the treatment outcomes for patients with chronic myeloid leukemia (CML). Bosutinib is a second-generation TKI that has demonstrated high efficacy and safety in clinical trials in firstand subsequent-line therapy of CML. Aim. To evaluate the long-term efficacy and safety of bosutinib in real-world clinical practice. Mat erials and methods. In our retrospective study all patients in the first chronic phase of CML who had ever received bosutinib therapy as their first, second, or third TKI were included. Only 4 patients (2 men) aged from 30 to 41 years received bosutinib as first TKI. Bosutinib was administered as second or third TKI to 19 patients (12 men) with a median age of 50 (31–71) and 17 patients (8 men) with a median age of 49.8 (21–70), respectively. Most patients had a long history of CML and most of them were resistant to previous TKIs. Results. All four patients who received bosutinib in the first-line achieved a complete hematological response (CHR), and three (75%) of them achieved a complete cytogenetic response (CCR) and a major molecular response (MMR). All 3 patients with MMR continued therapy for more than 16 years without significant adverse events. Among patients with bosutinib treatment after failure of imatinib or 2 TKIs, the CHR was achieved in most cases, and major cytogenetic response (MCR) was achieved in 7/19 (36.8%) and 6/17 (35.3%) cases. During the observation period, the median overall survival was not reached. There were few cases of bosutinib discontinuation due to drug intolerance. Long-term use of the drug did not lead to serious delayed side effects, including cardiovascular complications, associated with bosutinib therapy. Conclusions. Thus, in our group of patients with long-term observation, bosutinib showed not only a high frequency of achieving an optimal response in all lines of therapy in CP CML, but also the absence of severe remote complications, both hematological and non-hematological.