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No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

  • Sohn, Sang Kyun (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Moon, Joon Ho (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Lee, In Hee (Department of Hematology/Oncology, Kyungpook National University Hospital) ;
  • Ahn, Jae Sook (Department of Hematology/Oncology, Chonnam National University Hwasun Hospital) ;
  • Kim, Hyeoung Joon (Department of Hematology/Oncology, Chonnam National University Hwasun Hospital) ;
  • Chung, Joo Seop (Department of Hematology/Oncology, Pusan National University Hospital) ;
  • Shin, Ho Jin (Department of Hematology/Oncology, Pusan National University Hospital) ;
  • Park, Sung Woo (Department of Hematology/Oncology, Pusan National University Hospital) ;
  • Lee, Won Sik (Department of Hematology/Oncology, Inje University Busan Baik Hospital) ;
  • Lee, Sang Min (Department of Hematology/Oncology, Inje University Busan Baik Hospital) ;
  • Kim, Hawk (Department of Hematology/Oncology, Ulsan University Hospital) ;
  • Lee, Ho Sup (Department of Hematology/Oncology, Kosin University Gospel Hospital) ;
  • Kim, Yang Soo (Department of Hematology/Oncology, Kosin University Gospel Hospital) ;
  • Cho, Yoon Young (Department of Hematology/Oncology, Daegu Catholic University Medical Center) ;
  • Bae, Sung Hwa (Department of Hematology/Oncology, Daegu Catholic University Medical Center) ;
  • Lee, Ji Hyun (Department of Hematology/Oncology, Dong-A University Hospital) ;
  • Kim, Sung Hyun (Department of Hematology/Oncology, Dong-A University Hospital) ;
  • Song, Ik Chan (Department of Hematology/Oncology, Chungnam National University Hospital) ;
  • Kwon, Ji Hyun (Department of Hematology/Oncology, Chungbuk National University Hospital) ;
  • Lee, Yoo Jin (Department of Hematology/Oncology, Kyungpook National University Hospital)
  • 투고 : 2016.12.21
  • 심사 : 2017.04.05
  • 발행 : 2018.11.01

초록

Background/Aims: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were $53.1%{\pm}10.7%$ for allo-HCT with HMA, $75%{\pm}21.7%$ for allo-HCT without HMA, $17.3%{\pm}3.6%$ for HMA, and $20.8%{\pm}6.9%$ for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ${\geq}65years$ (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. Conclusions: For the H/VH risk group, very poor cytogenetic risk, age ${\geq}65years$, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

키워드

과제정보

연구 과제 주관 기관 : Kyungpook National University

참고문헌

  1. Greenberg PL, Stone RM, Bejar R, et al. Myelodysplastic syndromes, version 2.2015. J Natl Compr Canc Netw 2015;13:261-272. https://doi.org/10.6004/jnccn.2015.0038
  2. Oran B, Popat U, Andersson B, Champlin R. Allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk 2013;13 Suppl 2:S282-S288. https://doi.org/10.1016/j.clml.2013.07.012
  3. Sekeres MA. The euphoria of hypomethylating agents in MDS and AML: is it justified? Best Pract Res Clin Haematol 2013;26:275-278. https://doi.org/10.1016/j.beha.2013.10.001
  4. Steensma DP. Can hypomethylating agents provide a platform for curative therapy in myelodysplastic syndromes? Best Pract Res Clin Haematol 2012;25:443-451. https://doi.org/10.1016/j.beha.2012.10.007
  5. Kim Y, Kim IH, Kim HJ, et al. Multicenter study evaluating the impact of hypomethylating agents as bridging therapy to hematopoietic stem cell transplantation in myelodysplastic syndromes. Int J Hematol 2014;99:635-643. https://doi.org/10.1007/s12185-014-1549-3
  6. Oshikawa G, Yoshioka K, Takahashi Y, et al. Impact of prior azacitidine on the outcome of allogeneic hematopoietic transplantation for myelodysplastic syndrome. Pathol Oncol Res 2015;21:1037-1043. https://doi.org/10.1007/s12253-015-9933-8
  7. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:2454-2465.
  8. Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 2006;24:3895-3903. https://doi.org/10.1200/JCO.2005.05.4346
  9. Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006;108:419-425. https://doi.org/10.1182/blood-2005-10-4149
  10. Vigorito AC, Campregher PV, Storer BE, et al. Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD. Blood 2009;114:702-708.
  11. Silverman LR, Fenaux P, Mufti GJ, et al. Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Cancer 2011;117:2697-2702. https://doi.org/10.1002/cncr.25774
  12. Becker H, Suciu S, Ruter BH, et al. Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt): results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). Ann Hematol 2015;94:2003-2013. https://doi.org/10.1007/s00277-015-2489-6
  13. Musto P, Maurillo L, Spagnoli A, et al. Azacitidine for the treatment of lower risk myelodysplastic syndromes: a retrospective study of 74 patients enrolled in an Italian named patient program. Cancer 2010;116:1485-1494. https://doi.org/10.1002/cncr.24894
  14. Lubbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate-or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol 2011;29:1987-1996. https://doi.org/10.1200/JCO.2010.30.9245
  15. Sekeres MA, Cutler C. How we treat higher-risk myelodysplastic syndromes. Blood 2014;123:829-836. https://doi.org/10.1182/blood-2013-08-496935
  16. Lubbert M, Suciu S, Hagemeijer A, et al. Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group. Ann Hematol 2016;95:191-199. https://doi.org/10.1007/s00277-015-2547-0
  17. Brierley CK, Steensma DP. Thrombopoiesis-stimulating agents and myelodysplastic syndromes. Br J Haematol 2015;169:309-323. https://doi.org/10.1111/bjh.13285
  18. Gauthier J, Damaj G, Yakoub-Agha I. The role of pre-transplant debulking treatment in patients undergoing allogeneic stem cell transplantation for high-risk myelodysplastic syndrome. Bull Cancer 2015;102:340-348. https://doi.org/10.1016/j.bulcan.2015.02.009
  19. Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood 2014;124:2705-2712.
  20. Itzykson R, Kosmider O, Cluzeau T, et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 2011;25:1147-1152. https://doi.org/10.1038/leu.2011.71
  21. Wermke M, Gloaguen S, Platzbecker U. Preparing patients with myelodysplastic syndrome for transplant when is pre-transplant cytoreductive therapy appropriate? Curr Hematol Malig Rep 2015;10:329-333. https://doi.org/10.1007/s11899-015-0276-z
  22. Sohn SK, Moon JH. Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS. Crit Rev Oncol Hematol 2015;95:243-250. https://doi.org/10.1016/j.critrevonc.2015.03.004
  23. Oran B, Kongtim P, Popat U, et al. Cytogenetics, donor type, and use of hypomethylating agents in myelodysplastic syndrome with allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2014;20:1618-1625. https://doi.org/10.1016/j.bbmt.2014.06.022
  24. Martino M, Fedele R, Moscato T, Ronco F. Optimizing outcomes following allogeneic hematopoietic progenitor cell transplantation in AML: the role of hypomethylating agents. Curr Cancer Drug Targets 2013;13:661-669. https://doi.org/10.2174/15680096113139990005