Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia

Philipp Le Coutre, Oliver G. Ottmann, Francis Giles, Dong Wook Kim, Jorge Cortes, Norbert Gattermann, Jane F. Apperley, Richard A. Larson, Elisabetta Abruzzese, Stephen G. O'Brien, Kazimierz Kuliczkowski, Andreas Hochhaus, Francois Xavier Mahon, Giuseppe Saglio, Marco Gobbi, Yok Lam Kwong, Michele Baccarani, Timothy Hughes, Giovanni Martinelli, Jerald P. Radich & 3 others Ming Zheng, Yaping Shou, Hagop Kantarjian

Research output: Contribution to journalArticle

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Abstract

Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials. gov as NCT00384228.

LanguageEnglish
Pages1834-1839
Number of pages6
JournalBlood
Volume111
Issue number4
DOIs
Publication statusPublished - 15 Feb 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Le Coutre, Philipp ; Ottmann, Oliver G. ; Giles, Francis ; Kim, Dong Wook ; Cortes, Jorge ; Gattermann, Norbert ; Apperley, Jane F. ; Larson, Richard A. ; Abruzzese, Elisabetta ; O'Brien, Stephen G. ; Kuliczkowski, Kazimierz ; Hochhaus, Andreas ; Mahon, Francois Xavier ; Saglio, Giuseppe ; Gobbi, Marco ; Kwong, Yok Lam ; Baccarani, Michele ; Hughes, Timothy ; Martinelli, Giovanni ; Radich, Jerald P. ; Zheng, Ming ; Shou, Yaping ; Kantarjian, Hagop. / Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. In: Blood. 2008 ; Vol. 111, No. 4. pp. 1834-1839.
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title = "Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia",
abstract = "Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47{\%}; 95{\%} confidence interval [CI], 38{\%}-56{\%}). Major cytogenetic response (MCyR) was observed in 35 patients (29{\%}; 95{\%} CI, 21{\%}-39{\%}). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79{\%} (95{\%} CI, 70{\%}-87{\%}). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35{\%}) and neutropenia (21{\%}). Grade 3 or higher bilirubin and lipase elevations occurred in 9{\%} and 18{\%} of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials. gov as NCT00384228.",
author = "{Le Coutre}, Philipp and Ottmann, {Oliver G.} and Francis Giles and Kim, {Dong Wook} and Jorge Cortes and Norbert Gattermann and Apperley, {Jane F.} and Larson, {Richard A.} and Elisabetta Abruzzese and O'Brien, {Stephen G.} and Kazimierz Kuliczkowski and Andreas Hochhaus and Mahon, {Francois Xavier} and Giuseppe Saglio and Marco Gobbi and Kwong, {Yok Lam} and Michele Baccarani and Timothy Hughes and Giovanni Martinelli and Radich, {Jerald P.} and Ming Zheng and Yaping Shou and Hagop Kantarjian",
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Le Coutre, P, Ottmann, OG, Giles, F, Kim, DW, Cortes, J, Gattermann, N, Apperley, JF, Larson, RA, Abruzzese, E, O'Brien, SG, Kuliczkowski, K, Hochhaus, A, Mahon, FX, Saglio, G, Gobbi, M, Kwong, YL, Baccarani, M, Hughes, T, Martinelli, G, Radich, JP, Zheng, M, Shou, Y & Kantarjian, H 2008, 'Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia', Blood, vol. 111, no. 4, pp. 1834-1839. https://doi.org/10.1182/blood-2007-04-083196

Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. / Le Coutre, Philipp; Ottmann, Oliver G.; Giles, Francis; Kim, Dong Wook; Cortes, Jorge; Gattermann, Norbert; Apperley, Jane F.; Larson, Richard A.; Abruzzese, Elisabetta; O'Brien, Stephen G.; Kuliczkowski, Kazimierz; Hochhaus, Andreas; Mahon, Francois Xavier; Saglio, Giuseppe; Gobbi, Marco; Kwong, Yok Lam; Baccarani, Michele; Hughes, Timothy; Martinelli, Giovanni; Radich, Jerald P.; Zheng, Ming; Shou, Yaping; Kantarjian, Hagop.

In: Blood, Vol. 111, No. 4, 15.02.2008, p. 1834-1839.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia

AU - Le Coutre, Philipp

AU - Ottmann, Oliver G.

AU - Giles, Francis

AU - Kim, Dong Wook

AU - Cortes, Jorge

AU - Gattermann, Norbert

AU - Apperley, Jane F.

AU - Larson, Richard A.

AU - Abruzzese, Elisabetta

AU - O'Brien, Stephen G.

AU - Kuliczkowski, Kazimierz

AU - Hochhaus, Andreas

AU - Mahon, Francois Xavier

AU - Saglio, Giuseppe

AU - Gobbi, Marco

AU - Kwong, Yok Lam

AU - Baccarani, Michele

AU - Hughes, Timothy

AU - Martinelli, Giovanni

AU - Radich, Jerald P.

AU - Zheng, Ming

AU - Shou, Yaping

AU - Kantarjian, Hagop

PY - 2008/2/15

Y1 - 2008/2/15

N2 - Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials. gov as NCT00384228.

AB - Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials. gov as NCT00384228.

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U2 - 10.1182/blood-2007-04-083196

DO - 10.1182/blood-2007-04-083196

M3 - Article

VL - 111

SP - 1834

EP - 1839

JO - Blood

T2 - Blood

JF - Blood

SN - 0006-4971

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