DOI QR코드

DOI QR Code

만성골수성백혈병의 최신동향

Recent Advances of Management for Chronic Myeloid Leukemia

  • 김동욱 (가톨릭대학교 서울성모병원 혈액내과)
  • Kim, Dong-Wook (Department of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine)
  • 발행 : 2012.12.01

초록

The clinical outcome for patients with chronic myeloid leukemia (CML) has improved radically in the past 15 years. Imatinib led to high rates of complete cytogenetic responses and improved survival for patients with this disease. However, approximately 25-35% of patients in chronic phase treated with imatinib developed treatment failure. Development of next-generation Tyrosine kinase inhibitors (TKIs), such as dasatinib, nilotinib, radotinib, bosutinib, and ponatinib, has provided new therapeutic option for the patients resistant or intolerant to imatinib. Second generation (2G) TKIs were active in most clinically relevant BCR-ABL mutations, except highly resistant T315I. Through the phase 3 international randomized studies of 2G TKIs (dasatinib, nilotinib, and bosutinib) vs. imatinib, 2G TKIs emerged as the standard treatment for CML and have successfully prolonged the duration of both the chronic phase (CP) and the disease-free state. The majority of newly diagnosed patients treated with 2G TKIs achieved a complete cytogenetic response (CCyR), and over time, most of these eventually achieved major molecular responses (MMRs) and even complete molecular responses (CMRs). More recently, both dasatinib and nilotinib were approved for frontline use, and dasatinib, nilotinib, radotinib and bosutinib were approved for second-line use in patients with CML. Ponatinib represents the third generation of TKI, and this drug has been developed with the aim of targeting a specific BCR-ABL1 mutation (T315I), which arises in the setting of prolonged TKI therapy and leads to resistance to all commercially available TKIs.

키워드

참고문헌

  1. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031-1037. https://doi.org/10.1056/NEJM200104053441401
  2. Kim D, Goh HG, Kim SH, et al. Comprehensive therapeutic outcomes of frontline imatinib mesylate in newly diagnosed chronic phase chronic myeloid leukemia patients in Korea: feasibility assessment of current ELN recommendation. Int J Hematol 2012;96:47-57. https://doi.org/10.1007/s12185-012-1093-y
  3. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-2259. https://doi.org/10.1056/NEJMoa0912614
  4. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-2270. https://doi.org/10.1056/NEJMoa1002315
  5. Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-1035. https://doi.org/10.1016/S1470-2045(10)70233-3
  6. Hochhaus A, O'Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009;23:1054-1061. https://doi.org/10.1038/leu.2009.38
  7. De Lavallade H, Apperley JF, Khorashad JS, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008;26:3358-3363. https://doi.org/10.1200/JCO.2007.15.8154
  8. Cortes JE, Baccarani M, Guilhot F, et al. Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 2010;28:424-430. Erratum in: J Clin Oncol 2010;28:2314. https://doi.org/10.1200/JCO.2009.25.3724
  9. Goh HG, Kim YJ, Kim DW, et al. Previous best responses can be re-achieved by resumption after imatinib discontinuation in patients with chronic myeloid leukemia: implication for intermittent imatinib therapy. Leuk Lymphoma 2009;50:944-951. https://doi.org/10.1080/10428190902926973
  10. Kantarjian HM, Hochhaus A, Saglio G, et al. Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. Lancet Oncol 2011;12:841-851. https://doi.org/10.1016/S1470-2045(11)70201-7
  11. Larson RA, Hochhaus A, Hughes TP, et al. Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 2012;26:2197-2203. https://doi.org/10.1038/leu.2012.134
  12. Hochhaus A, Shah N, Cortes J, et al. Efficacy and safety of dasatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): minimum 24-month follow-up from the DASISION trial. Haematologica 2011;96(Suppl 2):A422.
  13. Hochhaus A, Shah NP, Cortes J, et al. Dasatinib versus imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): DASISION 3-year follow-up. J Clin Oncol 2012; June, abst 6505.
  14. Brummendorf T, Gambacorti-Passerini C, Cortes J, et al. The BELA trial: bosutinib versus imatinib in patients with chronic phase chronic myeloid leukemia; 18-month follow-up. Haematologica 2011;96(Suppl 2):A204. https://doi.org/10.3324/haematol.2010.029082
  15. Cortes JE, Kim DW, Kantarjian HM, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 2012;30:3486-3492. https://doi.org/10.1200/JCO.2011.38.7522
  16. Khoury HJ, Guilhot F, Hughes TP, Kim DW, Cortes JE. Dasatinib treatment for Philadelphia chromosome-positive leukemias: practical considerations. Cancer 2009;115:1381-1394. https://doi.org/10.1002/cncr.24155
  17. Cortes JE, Kantarjian HM, Brummendorf TH, et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 2011;118:4567-4576. https://doi.org/10.1182/blood-2011-05-355594
  18. Hughes T, Saglio G, Branford S, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase. J Clin Oncol 2009;27:4204-4210. https://doi.org/10.1200/JCO.2009.21.8230
  19. Muller MC, Cortes JE, Kim DW, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood 2009;114:4944-4953. https://doi.org/10.1182/blood-2009-04-214221
  20. Khoury HJ, Cortes JE, Kantarjian HM, et al. Bosutinibis active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood 2012;119:3403-3412. https://doi.org/10.1182/blood-2011-11-390120

피인용 문헌

  1. Korean Guidelines for Treating Chronic Myelogenous Leukemia - The Korean Society of Hematology Chronic Myelogenous Leukemia Working Party vol.88, pp.4, 2012, https://doi.org/10.3904/kjm.2015.88.4.406
  2. Chronic Myeloid Leukemia Following Radioactive Iodine Treatment for Thyroid Cancer: Two Case Reports and a Literature Review vol.91, pp.1, 2012, https://doi.org/10.3904/kjm.2016.91.1.70