Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib

Jorge E. Cortes, Hanna J. Khoury, Hagop M. Kantarjian, Jeff H. Lipton, Dong Wook Kim, Philippe Schafhausen, Ewa Matczak, Eric Leip, Kay Noonan, Tim H. Brümmendorf, Carlo Gambacorti-Passerini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1206-1214
Number of pages9
JournalAmerican Journal of Hematology
Volume91
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

Fingerprint

Leukemia, Myeloid, Chronic Phase
Cytogenetics
Basophils
src-Family Kinases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Thrombocytopenia
Protein-Tyrosine Kinases
Nausea
Vomiting
Disease Progression
Diarrhea
Therapeutics
Safety
Survival
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Dasatinib
bosutinib
Incidence

ASJC Scopus subject areas

  • Hematology

Cite this

Cortes, J. E., Khoury, H. J., Kantarjian, H. M., Lipton, J. H., Kim, D. W., Schafhausen, P., ... Gambacorti-Passerini, C. (2016). Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. American Journal of Hematology, 91(12), 1206-1214. https://doi.org/10.1002/ajh.24536

Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. / Cortes, Jorge E.; Khoury, Hanna J.; Kantarjian, Hagop M.; Lipton, Jeff H.; Kim, Dong Wook; Schafhausen, Philippe; Matczak, Ewa; Leip, Eric; Noonan, Kay; Brümmendorf, Tim H.; Gambacorti-Passerini, Carlo.

In: American Journal of Hematology, Vol. 91, No. 12, 01.12.2016, p. 1206-1214.

Research output: Contribution to journalArticle

Cortes, JE, Khoury, HJ, Kantarjian, HM, Lipton, JH, Kim, DW, Schafhausen, P, Matczak, E, Leip, E, Noonan, K, Brümmendorf, TH & Gambacorti-Passerini, C 2016, 'Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib', American Journal of Hematology, vol. 91, no. 12, pp. 1206-1214. https://doi.org/10.1002/ajh.24536
Cortes, Jorge E. ; Khoury, Hanna J. ; Kantarjian, Hagop M. ; Lipton, Jeff H. ; Kim, Dong Wook ; Schafhausen, Philippe ; Matczak, Ewa ; Leip, Eric ; Noonan, Kay ; Brümmendorf, Tim H. ; Gambacorti-Passerini, Carlo. / Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. In: American Journal of Hematology. 2016 ; Vol. 91, No. 12. pp. 1206-1214.
@article{b39053c4f5774ea7a4d861aebef723a0,
title = "Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib",
abstract = "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.",
author = "Cortes, {Jorge E.} and Khoury, {Hanna J.} and Kantarjian, {Hagop M.} and Lipton, {Jeff H.} and Kim, {Dong Wook} and Philippe Schafhausen and Ewa Matczak and Eric Leip and Kay Noonan and Br{\"u}mmendorf, {Tim H.} and Carlo Gambacorti-Passerini",
year = "2016",
month = "12",
day = "1",
doi = "10.1002/ajh.24536",
language = "English (US)",
volume = "91",
pages = "1206--1214",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "12",

}

TY - JOUR

T1 - Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib

AU - Cortes, Jorge E.

AU - Khoury, Hanna J.

AU - Kantarjian, Hagop M.

AU - Lipton, Jeff H.

AU - Kim, Dong Wook

AU - Schafhausen, Philippe

AU - Matczak, Ewa

AU - Leip, Eric

AU - Noonan, Kay

AU - Brümmendorf, Tim H.

AU - Gambacorti-Passerini, Carlo

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84993972082&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84993972082&partnerID=8YFLogxK

U2 - 10.1002/ajh.24536

DO - 10.1002/ajh.24536

M3 - Article

C2 - 27531525

AN - SCOPUS:84993972082

VL - 91

SP - 1206

EP - 1214

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 12

ER -