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. RadichMing Zheng, Yaping Shou, Hagop Kantarjian

Research output: Contribution to journalArticle

248 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1834-1839
Number of pages6
JournalBlood
Volume111
Issue number4
DOIs
StatePublished - Feb 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Le Coutre, P., Ottmann, O. G., Giles, F., Kim, D. W., Cortes, J., Gattermann, N., Apperley, J. F., Larson, R. A., Abruzzese, E., O'Brien, S. G., Kuliczkowski, K., Hochhaus, A., Mahon, F. X., Saglio, G., Gobbi, M., Kwong, Y. L., Baccarani, M., Hughes, T., Martinelli, G., ... 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, 111(4), 1834-1839. https://doi.org/10.1182/blood-2007-04-083196