International Journal of Hematology

DOI: 10.1007/s12185-012-1026-9 Pages: 409-419

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

1. NTT Kanto Medical Center, Division of Hematology

2. The Institute of Medical Science, The University of Tokyo

3. Kinki University School of Medicine

4. National Cancer Center Hospital

5. Saitama Medical University, International Medical Center

6. Tokyo Medical University Hospital

7. Chiba University Hospital

8. Kumamoto University Hospital

9. Hiroshima University Hospital

10. Japanese Red Cross Nagoya First Hospital

11. Nagasaki University Hospital

12. Keio University Hospital

13. Osaka University Hospital

14. Hyogo College of Medicine

15. The Jikei University Daisan Hospital

16. Jichi Medical University Hospital

17. Novartis Pharma Japan

18. Nagoya University Hospital

19. National Hospital Organization Osaka Minami Medical Center

20. Hiroshima City Asa Hospital

Correspondence to:
Kensuke Usuki
Tel: +81-3-34486111
Fax: +81-3-34486553
Email: usuki@east.ntt.co.jp

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Abstract

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.

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