Abstract
Imatinib has dramatically improved long-term survival of chronic myelogenous leukemia (CML) patients. To analyze its efficacy in a practical setting, we registered most of CML patients in Nagasaki Prefecture of Japan. Of these, 73 patients received imatinib as an initial therapy. The overall survival rate of these patients was 88.7% at 6 years, and the cumulative complete cytogenetic response rate was 82.5% at 18 months. These results are comparable with the data of other reports including the IRIS study; however, the administered imatinib dose was smaller in our study than that in other reports. To address these discrepancies, we measured the trough concentration of imatinib among 35 patients. Although 39% of the patients were administered less than 400 mg/day, the trough level was comparable to those of previous reports. The trough level of imatinib showed a significant relationship with its efficacy, and was clearly related to dose of imatinib administrated and dose of imatinib divided by body surface area (BSA). Considering the smaller BSA of Japanese patients as compared to those of foreign origin, the results suggest that a lower dose of imatinib could maintain enough trough level and provided excellent results for the treatment of CML in our registry.
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References
Hehlmann R, Hochhaus A, Baccarani M, European LeukemiaNet. Chronic myeloid leukaemia. Lancet. 2007;370:342–50. doi:10.1016/S0140-6736(07)61165-9.
Borthakur G, Cortes JE. Imatinib mesylate treat chronic myelogenous leukemia. Int J Hematol. 2004;79:411–9.
Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005;105:2640–53. doi:10.1182/blood-2004-08-3097.
O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004. doi:10.1056/NEJMoa022457.
Hughes TM, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003;349:1423–32. doi:10.1056/NEJMoa030513.
Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17. doi:10.1056/NEJMoa062867.
Matsuo E, Miyazaki Y, Tsutsumi C, Inoue Y, Yamasaki R, Hata T, et al. Imatinib provides durable molecular and cytogenetic responses in a practical setting for both newly diagnosed and previously treated chronic myelogenous leukemia: a study in Nagasaki Prefecture, Japan. Int J Hematol. 2007;85:132–9. doi:10.1532/IJH97.06157.
Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Tough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood. 2007;109:3496–9. doi:10.1182/blood-2006-07-036012.
Larson RA, Drucker BJ, Guiihot F, O’Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022–8. doi:10.1182/blood-2007-10-116475.
Bakhtiar R, Lohne J, Ramos L, Khemani L, Hayes M, Tse M. High-throughput quantification of the anti-leukemia drug STI571 (Gleevec™) and its main metabolite (GCP 74588) in human plasma using liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2002;768:325–40.
Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108:1809–20. doi:10.1182/blood-2006-02-005686.
Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44:879–94. doi:10.2165/00003088-200544090-00001.
Peng B, Hayes M, Resta D, Brian ARP, Druker BJ, Talpaz M, et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol. 2004;22:935–42. doi:10.1200/JCO.2004.03.050.
Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354:2531–41. doi:10.1056/NEJMoa055229.
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. N Engl J Med. 2006;354:2542–51. doi:10.1056/NEJMoa055104.
Jabbour E, Cortes J, Kantarjian HM, Giralt S, Jones D, Giles F, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood. 2006;108:1421–3. doi:10.1182/blood-2006-02-001933.
Kantarjian H, Talpaz M, O’Brien S, Garcia-Manero G, Verstovsed S, Giles F, et al. High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. Blood. 2004;103:2873–8.
Acknowledgments
We would like to thank Dr. T Matsuo for his support and Ms. N Shirahama for her assistance.
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The affiliation details of the members of Nagasaki CML Study Group are given in Appendix.
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Appendix
Members of the Nagasaki CML Study Group are as follows: S. Atogami, and H. Kawaguchi (Nagasaki Municipal Medical Center), M. Yamamura (Nagasaki Municipal Hospital), T. Joh, Y. Takasaki, and M. Tawara (The Japanese Red Cross Nagasaki Atomic Bomb Hospital), H. Tsushima (St. Francis Hospital), Y. Moriuchi, Y. Onimaru, R. Yamasaki, and Y. Sawayama (Sasebo Municipal General Hospital), S. Yoshida, Y. Inoue, and Y. Moriwaki (National Hospital Organization, Nagasaki Medical Center), D. Ogawa (Nagasaki Prefectural Shimabara Hospital), H. Soda (Health Insurance, Isahaya General Hospital), H. Nonaka (Japan Labour Health and Welfare Organization, Nagasaki Rosai Hospital), S. Ikeda (Hirado Municipal Hospital), I. Jinnai (Saitama Medical School), K. Kuriyama (University of the Ryukyus), M. Kusano (Senju Hospital), S. Koida (Gotoh Central Hospital), Y. Matsuo (Sankoukai Obama Hospital) and other authors in Nagasaki University.
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Sakai, M., Miyazaki, Y., Matsuo, E. et al. Long-term efficacy of imatinib in a practical setting is correlated with imatinib trough concentration that is influenced by body size: a report by the Nagasaki CML Study Group. Int J Hematol 89, 319–325 (2009). https://doi.org/10.1007/s12185-009-0263-z
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DOI: https://doi.org/10.1007/s12185-009-0263-z