Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL

Hagop Kantarjian, Francis Giles, Lydia Wunderle, Kapil Bhalla, Susan O'Brien, Barbara Wassmann, Chiaki Tanaka, Paul Manley, Patricia Rae, William Mietlowski, Kathy Bochinski, Andreas Hochhaus, James D. Griffin, Dieter Hoelzer, Maher Albitar, Margaret Dugan, Jorge Cortes, Leila Alland, Oliver G. Ottmann

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50. METHODS: In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily. RESULTS: Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission. CONCLUSIONS: Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML.

Original languageEnglish (US)
Pages (from-to)2542-2551
Number of pages10
JournalNew England Journal of Medicine
Volume354
Issue number24
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

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Philadelphia Chromosome
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cytogenetics
Hyperbilirubinemia
Exanthema
Protein-Tyrosine Kinases
Safety
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
Imatinib Mesylate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kantarjian, H., Giles, F., Wunderle, L., Bhalla, K., O'Brien, S., Wassmann, B., ... Ottmann, O. G. (2006). Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. New England Journal of Medicine, 354(24), 2542-2551. https://doi.org/10.1056/NEJMoa055104

Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. / Kantarjian, Hagop; Giles, Francis; Wunderle, Lydia; Bhalla, Kapil; O'Brien, Susan; Wassmann, Barbara; Tanaka, Chiaki; Manley, Paul; Rae, Patricia; Mietlowski, William; Bochinski, Kathy; Hochhaus, Andreas; Griffin, James D.; Hoelzer, Dieter; Albitar, Maher; Dugan, Margaret; Cortes, Jorge; Alland, Leila; Ottmann, Oliver G.

In: New England Journal of Medicine, Vol. 354, No. 24, 15.06.2006, p. 2542-2551.

Research output: Contribution to journalArticle

Kantarjian, H, Giles, F, Wunderle, L, Bhalla, K, O'Brien, S, Wassmann, B, Tanaka, C, Manley, P, Rae, P, Mietlowski, W, Bochinski, K, Hochhaus, A, Griffin, JD, Hoelzer, D, Albitar, M, Dugan, M, Cortes, J, Alland, L & Ottmann, OG 2006, 'Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL', New England Journal of Medicine, vol. 354, no. 24, pp. 2542-2551. https://doi.org/10.1056/NEJMoa055104
Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. New England Journal of Medicine. 2006 Jun 15;354(24):2542-2551. https://doi.org/10.1056/NEJMoa055104
Kantarjian, Hagop ; Giles, Francis ; Wunderle, Lydia ; Bhalla, Kapil ; O'Brien, Susan ; Wassmann, Barbara ; Tanaka, Chiaki ; Manley, Paul ; Rae, Patricia ; Mietlowski, William ; Bochinski, Kathy ; Hochhaus, Andreas ; Griffin, James D. ; Hoelzer, Dieter ; Albitar, Maher ; Dugan, Margaret ; Cortes, Jorge ; Alland, Leila ; Ottmann, Oliver G. / Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. In: New England Journal of Medicine. 2006 ; Vol. 354, No. 24. pp. 2542-2551.
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AU - O'Brien, Susan

AU - Wassmann, Barbara

AU - Tanaka, Chiaki

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AU - Rae, Patricia

AU - Mietlowski, William

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AU - Hochhaus, Andreas

AU - Griffin, James D.

AU - Hoelzer, Dieter

AU - Albitar, Maher

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AU - Alland, Leila

AU - Ottmann, Oliver G.

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N2 - BACKGROUND: Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50. METHODS: In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily. RESULTS: Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission. CONCLUSIONS: Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML.

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