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Factors influencing long‐term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib
Author(s) -
Brümmendorf Tim H.,
Cortes Jorge E.,
Khoury Hanna J.,
Kantarjian Hagop M.,
Kim DongWook,
Schafhausen Philippe,
Conlan Maureen G.,
Shapiro Mark,
Turnbull Kathleen,
Leip Eric,
GambacortiPasserini Carlo,
Lipton Jeff H.
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13801
Subject(s) - bosutinib , medicine , imatinib , tolerability , cumulative incidence , adverse effect , discontinuation , oncology , gastroenterology , myeloid leukemia , nilotinib , cohort
Summary The dual SRC / ABL 1 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 ( NCT 00261846) 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 ( MC yR) rate [95% confidence interval ( CI )], was 59% (53–65%); Kaplan‐Meier ( KM ) probability of maintaining MC yR 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 MC yR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MC yR, 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 ‐ ABL 1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver‐related AE s. Bosutinib demonstrates durable efficacy and manageable toxicity in IM ‐R/ IM ‐I CP ‐ CML patients.