Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance

Hagop M. Kantarjian, Francis Giles, Norbert Gattermann, Kapil Bhalla, Giuliana Alimena, Francesca Palandri, Gert J. Ossenkoppele, Franck Emmanuel Nicolini, Stephen G. O'Brien, Mark R Litzow, Ravi Bhatia, Francisco Cervantes, Ariful Haque, Yaping Shou, Debra J. Resta, Aaron Weitzman, Andreas Hochhaus, Philipp Le Coutre

Research output: Contribution to journalArticle

564 Citations (Scopus)

Abstract

Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in preclinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph ≤ 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707.

Original languageEnglish (US)
Pages (from-to)3540-3546
Number of pages7
JournalBlood
Volume110
Issue number10
DOIs
StatePublished - Nov 15 2007

Fingerprint

Leukemia, Myeloid, Chronic Phase
Philadelphia Chromosome
Chromosomes
Protein-Tyrosine Kinases
Cytogenetics
Mutation
bcr-abl Fusion Proteins
Survival
Pericardial Effusion
Pleural Effusion
Neutropenia
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate
Labels
Clinical Trials
Safety

ASJC Scopus subject areas

  • Hematology

Cite this

Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. / Kantarjian, Hagop M.; Giles, Francis; Gattermann, Norbert; Bhalla, Kapil; Alimena, Giuliana; Palandri, Francesca; Ossenkoppele, Gert J.; Nicolini, Franck Emmanuel; O'Brien, Stephen G.; Litzow, Mark R; Bhatia, Ravi; Cervantes, Francisco; Haque, Ariful; Shou, Yaping; Resta, Debra J.; Weitzman, Aaron; Hochhaus, Andreas; Le Coutre, Philipp.

In: Blood, Vol. 110, No. 10, 15.11.2007, p. 3540-3546.

Research output: Contribution to journalArticle

Kantarjian, HM, Giles, F, Gattermann, N, Bhalla, K, Alimena, G, Palandri, F, Ossenkoppele, GJ, Nicolini, FE, O'Brien, SG, Litzow, MR, Bhatia, R, Cervantes, F, Haque, A, Shou, Y, Resta, DJ, Weitzman, A, Hochhaus, A & Le Coutre, P 2007, 'Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance', Blood, vol. 110, no. 10, pp. 3540-3546. https://doi.org/10.1182/blood-2007-03-080689
Kantarjian, Hagop M. ; Giles, Francis ; Gattermann, Norbert ; Bhalla, Kapil ; Alimena, Giuliana ; Palandri, Francesca ; Ossenkoppele, Gert J. ; Nicolini, Franck Emmanuel ; O'Brien, Stephen G. ; Litzow, Mark R ; Bhatia, Ravi ; Cervantes, Francisco ; Haque, Ariful ; Shou, Yaping ; Resta, Debra J. ; Weitzman, Aaron ; Hochhaus, Andreas ; Le Coutre, Philipp. / Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. In: Blood. 2007 ; Vol. 110, No. 10. pp. 3540-3546.
@article{9ca291d75317412f87b2b76037b897df,
title = "Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance",
abstract = "Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in preclinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph ≤ 35{\%}) was 48{\%}: complete (Ph = 0{\%}) in 31{\%}, and partial (Ph = 1{\%}-35{\%}) in 16{\%}. The estimated survival at 12 months was 95{\%}. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29{\%} of patients; pleural or pericardial effusions were observed in 1{\%} (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707.",
author = "Kantarjian, {Hagop M.} and Francis Giles and Norbert Gattermann and Kapil Bhalla and Giuliana Alimena and Francesca Palandri and Ossenkoppele, {Gert J.} and Nicolini, {Franck Emmanuel} and O'Brien, {Stephen G.} and Litzow, {Mark R} and Ravi Bhatia and Francisco Cervantes and Ariful Haque and Yaping Shou and Resta, {Debra J.} and Aaron Weitzman and Andreas Hochhaus and {Le Coutre}, Philipp",
year = "2007",
month = "11",
day = "15",
doi = "10.1182/blood-2007-03-080689",
language = "English (US)",
volume = "110",
pages = "3540--3546",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

TY - JOUR

T1 - Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance

AU - Kantarjian, Hagop M.

AU - Giles, Francis

AU - Gattermann, Norbert

AU - Bhalla, Kapil

AU - Alimena, Giuliana

AU - Palandri, Francesca

AU - Ossenkoppele, Gert J.

AU - Nicolini, Franck Emmanuel

AU - O'Brien, Stephen G.

AU - Litzow, Mark R

AU - Bhatia, Ravi

AU - Cervantes, Francisco

AU - Haque, Ariful

AU - Shou, Yaping

AU - Resta, Debra J.

AU - Weitzman, Aaron

AU - Hochhaus, Andreas

AU - Le Coutre, Philipp

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in preclinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph ≤ 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707.

AB - Nilotinib, an orally bioavailable, selective Bcr-Abl tyrosine kinase inhibitor, is 30-fold more potent than imatinib in preclinical models, and overcomes most imatinib resistant BCR-ABL mutations. In this phase 2 open-label study, 400 mg nilotinib was administered orally twice daily to 280 patients with Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia in chronic phase (CML-CP) after imatinib failure or intolerance. Patients had at least 6 months of follow-up and were evaluated for hematologic and cytogenetic responses, as well as for safety and overall survival. At 6 months, the rate of major cytogenetic response (Ph ≤ 35%) was 48%: complete (Ph = 0%) in 31%, and partial (Ph = 1%-35%) in 16%. The estimated survival at 12 months was 95%. Nilotinib was effective in patients harboring BCR-ABL mutations associated with imatinib resistance (except T315I), and also in patients with a resistance mechanism independent of BCR-ABL mutations. Adverse events were mostly mild to moderate, and there was minimal cross-intolerance with imatinib. Grades 3 to 4 neutropenia and thrombocytopenia were observed in 29% of patients; pleural or pericardial effusions were observed in 1% (none were severe). In summary, nilotinib is highly active and safe in patients with CML-CP after imatinib failure or intolerance. This clinical trial is registered at http://clinicaltrials.gov as ID no. NCT00109707.

UR - http://www.scopus.com/inward/record.url?scp=36348968931&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348968931&partnerID=8YFLogxK

U2 - 10.1182/blood-2007-03-080689

DO - 10.1182/blood-2007-03-080689

M3 - Article

VL - 110

SP - 3540

EP - 3546

JO - Blood

JF - Blood

SN - 0006-4971

IS - 10

ER -