Bosutinib is an Src/Abl tyrosine kinase inhibitor (TKI) indicated for adults with Ph+ chronic myeloid leukemia (CML) resistant/intolerant to prior TKIs. This long-term update of an ongoing phase 1/2 study evaluated the efficacy and safety of third-/fourth-line bosutinib in adults with chronic phase (CP) CML. Median durations of treatment and follow-up were 8.6 (range, 0.2–87.7) months and 32.7 (0.3–93.3) months, respectively. Cumulative confirmed complete hematologic response (cCHR) and major cytogenetic response (MCyR) rates were 74% (95% CI, 65–81%) and 40% (31–50%), respectively; Kaplan–Meier (K–M) probability of maintaining cCHR or MCyR at 4 years was 63% (95% CI, 50–73%) and 69% (52–81%). Cumulative incidence of on-treatment disease progression (PD)/death at 4 years was 24% (95% CI, 17–33%); K–M 4-year overall survival was 78% (68–85%). Baseline Ph+ cells ≤35 vs. ≥95% was prognostic of MCyR and CCyR by 3 and 6 months, increased baseline basophils was prognostic of PD/death, and no prior response to second-line TKI was prognostic of death. Common adverse events included diarrhea (83%), nausea (48%), vomiting (38%), and thrombocytopenia (39%). Bosutinib demonstrates durable efficacy and a toxicity profile similar to previous bosutinib studies in CP CML patients resistant/intolerant to multiple TKIs, representing an important treatment option for patients in this setting. This trial is registered at www.clinicaltrials.gov (NCT00261846). Am. J. Hematol. 91:1206–1214, 2016.
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