Original Article

International Journal of Hematology

, Volume 95, Issue 4, pp 409-419

First online:

Efficacy and safety of nilotinib in Japanese patients with imatinib-resistant or -intolerant Ph+ CML or relapsed/refractory Ph+ ALL: a 36-month analysis of a phase I and II study

  • Kensuke UsukiAffiliated withDivision of Hematology, NTT Kanto Medical Center Email author 
  • , Arinobu TojoAffiliated withThe Institute of Medical Science, The University of Tokyo
  • , Yasuhiro MaedaAffiliated withKinki University School of MedicineNational Hospital Organization Osaka Minami Medical Center
  • , Yukio KobayashiAffiliated withNational Cancer Center Hospital
  • , Akira MatsudaAffiliated withInternational Medical Center, Saitama Medical University
  • , Kazuma OhyashikiAffiliated withTokyo Medical University Hospital
  • , Chiaki NakasekoAffiliated withChiba University Hospital
  • , Tatsuya KawaguchiAffiliated withKumamoto University Hospital
  • , Hideo TanakaAffiliated withHiroshima University HospitalHiroshima City Asa Hospital
    • , Koichi MiyamuraAffiliated withJapanese Red Cross Nagoya First Hospital
    • , Yasushi MiyazakiAffiliated withNagasaki University Hospital
    • , Shinichiro OkamotoAffiliated withKeio University Hospital
    • , Kenji OritaniAffiliated withOsaka University Hospital
    • , Masaya OkadaAffiliated withHyogo College of Medicine
    • , Noriko UsuiAffiliated withThe Jikei University Daisan Hospital
    • , Tadashi NagaiAffiliated withJichi Medical University Hospital
    • , Taro AmagasakiAffiliated withNovartis Pharma Japan
    • , Aira WanajoAffiliated withNovartis Pharma Japan
    • , Tomoki NaoeAffiliated withNagoya University Hospital

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Although the tyrosine kinase inhibitor (TKI) imatinib is often used as first-line therapy for newly diagnosed chronic myelogenous leukemia (CML), some patients fail to respond, or become intolerant to imatinib. Nilotinib is a potent and selective second-generation TKI, with confirmed efficacy and tolerability in patients with imatinib-resistant or -intolerant CML. A phase I/II study was conducted in Japanese patients with imatinib-resistant or -intolerant CML or relapsed/refractory Ph+ acute lymphoblastic leukemia. Thirty-four patients were treated with nilotinib for up to 36 months. Major cytogenetic response was achieved in 15/16 patients (93.8%) with chronic-phase CML within a median of approximately 3 months. Major molecular response was achieved in 13/16 patients (81.3%). These responses were sustained at the time of the most recent evaluation in 13 patients and 11 patients, respectively. Hematologic and cytogenetic responses were also observed in patients with advanced CML. The BCR-ABL mutation associated with the most resistance to available TKIs, T315I, was observed in three patients. Common adverse events included rash, nasopharyngitis, leukopenia, neutropenia, thrombocytopenia, nausea, headache and vomiting. Most adverse events resolved following nilotinib dose interruptions/reductions. These results support the favorable long-term efficacy and tolerability of nilotinib in Japanese patients with imatinib-resistant or -intolerant chronic-phase chronic myeloid leukemia.


Chronic myeloid leukemia Acute lymphoblastic leukemia Tyrosine kinase inhibitors Nilotinib