Efficacy and safety of bosutinib in previously treated patients with chronic myeloid leukemia: final results from the BYOND trial

Abstract

This final analysis from the phase 4 BYOND trial reports outcomes with bosutinib in patients with previously treated chronic myeloid leukemia (CML); 163 patients with CML resistant/intolerant to previous tyrosine kinase inhibitors received bosutinib (starting dose: 500 mg QD). At study completion (median follow-up, 47.8 months), 48.1% (n = 75/156) of patients with Philadelphia chromosome-positive chronic phase CML were still receiving treatment. Among evaluable patients, 71.8% (95% CI, 63.9-78.9) and 59.7% (95% CI, 51.4-67.7) attained or maintained major molecular response (MMR) and molecular response (MR)⁴, respectively, at any time on treatment. The majority of patients achieved a deeper molecular response relative to baseline while on bosutinib. Kaplan-Meier probabilities (95% CI) of maintaining MMR and MR⁴ at 36 months were 87.2% (78.0-92.7) and 80.7% (69.4-88.1), respectively. At 48 months, the Kaplan-Meier overall survival rate was 88.3% (95% CI, 81.8-92.6); there were 17 deaths, including 2 that were considered CML related. Long-term adverse events (AEs) were consistent with the known safety profile of bosutinib, and no new safety issues were identified. The management of AEs through dose reduction maintained efficacy while improving tolerability. These results support the use of bosutinib in patients with previously treated CML.ClinicalTrials.gov, NCT02228382.

Fig. 1. Bosutinib dose over time in patients with Ph+ CP CML.

CML chronic myeloid leukemia, CP chronic phase, Ph+ Philadelphia chromosome–positive, QD once daily.

Fig. 2. Cumulative incidence of cytogenetic and molecular responses in patients with Ph+ CP CML.

A Cumulative incidence of CCyR in patients with Ph+ CP CML over 48 months. B Cumulative incidence of MMR in patients with Ph+ CP CML over 48 months. C Cumulative incidence of MR⁴ in patients with Ph+ CP CML over 48 months. D Cumulative incidence of MR^4.5 in patients with Ph+ CP CML over 48 months.

Fig. 3. TEAEs before and after dose reduction in patients with Ph+ CP CML.

Any grade TEAEs occurring in ≥20% of patients in the overall CP CML population (N = 156), or any grade TEAEs occurring in ≥20% before or after dose reduction at each dose level, or differences ≥10% in the incidence of any grade TEAEs before vs after dose reduction at each dose level were included. ALT alanine aminotransferase, AST aspartate aminotransferase, CML chronic myeloid leukemia, CP chronic phase, Ph+ Philadelphia chromosome–positive, QD once daily, TEAE treatment-emergent adverse event.