Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib

Tim H. Brümmendorf, Jorge E. Cortes, Hanna J. Khoury, Hagop M. Kantarjian, Dong Wook Kim, Philippe Schafhausen, Maureen G. Conlan, Mark Shapiro, Kathleen Turnbull, Eric Leip, Carlo Gambacorti-Passerini, Jeff H. Lipton

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The dual SRC/ABL1 tyrosine kinase inhibitor bosutinib is indicated for adults with Ph+ chronic myeloid leukaemia (CML) resistant/intolerant to prior therapy. This analysis of an ongoing phase 1/2 study (NCT00261846) assessed effects of baseline patient characteristics on long-term efficacy and safety of bosutinib 500 mg/day in adults with imatinib (IM)-resistant (IM-R; n = 196)/IM-intolerant (IM-I; n = 90) chronic phase (CP) CML. Median treatment duration was 24·8 months (median follow-up, 43·6 months). Cumulative major cytogenetic response (MCyR) rate [95% confidence interval (CI)], was 59% (53-65%); Kaplan-Meier (KM) probability of maintaining MCyR at 4 years was 75% (66-81%). Cumulative incidence of on-treatment progression/death at 4 years was 19% (95% CI, 15-24%); KM 2-year overall survival was 91% (87-94%). Significant baseline predictors of both MCyR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MCyR, prior interferon therapy and <6 months duration from diagnosis to IM treatment initiation and no interferon treatment before IM. The most common adverse event (AE) was diarrhoea (86%). Baseline bosutinib-sensitive BCR-ABL1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver-related AEs. Bosutinib demonstrates durable efficacy and manageable toxicity in IM-R/IM-I CP-CML patients.

Original languageEnglish (US)
Pages (from-to)97-110
Number of pages14
JournalBritish Journal of Haematology
Volume172
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Bosutinib
  • Chronic myeloid leukaemia
  • Chronic myeloid leukaemia
  • Second-line therapy
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Factors influencing long-term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib'. Together they form a unique fingerprint.

Cite this