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Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis

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Abstract

The present meta-analysis was undertaken to (1) assess erythroid response rates in myelodysplastic syndromes (MDS) patients treated with epoetin alfa as a monotherapy, (2) gain further insights into predictors of response rates, and (3) compare the erythroid response rates observed with epoetin alfa and darbepoetin alfa. A systematic review of studies from 1990 to 2006 in MDS patients treated with epoetin alfa or darbepoetin alfa was performed and yielded 30 studies evaluating a total of 1,314 patients (epoetin alfa: 22 studies, 925 patients; darbepoetin alfa: eight studies, 389 patients). Pooled estimates of erythroid response rates, stratified by the International Working Group criteria (IWGc) and treatment group, were calculated using random-effects meta-analysis methods. Univariate meta-regression analyses were further conducted to identify study characteristics associated with erythroid response rate. The pooled estimate of erythroid response rate was significantly higher for epoetin alfa IWGc studies (57.6%) as compared to non-IWGc studies (31.6%; p < 0.001). Study factors predictive of higher response rate in the epoetin alfa IWGc studies included higher proportion of patients with RA/RARS (p < 0.001), lower mean baseline serum erythropoietin level (p = 0.007), and fixed dosing regimen (p < 0.001). There was no significant difference in the pooled erythroid response rates between the two agents (epoetin alfa: 57.6% vs. darbepoetin alfa: 59.4%; p = 0.828). The current study reported significantly higher erythroid response rates predominantly in the more recent studies that primarily utilized IWGc to define response. With the use of standardized patient selection and response evaluation methods, epoetin alfa and darbepoetin alfa yielded comparable erythroid response rates in MDS patients.

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References

  1. Steensma DP, Bennett JM (2006) The myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc 81:104–130

    PubMed  Google Scholar 

  2. Catenacci DV, Schiller GJ (2005) Myelodysplastic syndromes: a comprehensive review. Blood Rev 19:301–319

    Article  PubMed  CAS  Google Scholar 

  3. Hellstrom-Lindberg E (2005) Management of anemia associated with myelodysplastic syndromes. Semin Oncol 42(2 Suppl 1):S10–S13

    CAS  Google Scholar 

  4. Greenberg P, Cox C, LeBeau MM et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89(6):2079–2088

    PubMed  CAS  Google Scholar 

  5. Cutler CS, Lee SJ, Greenberg P et al (2004) A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 104(2):579–585

    Article  PubMed  CAS  Google Scholar 

  6. Malcovati L, Porta MG, Pascutto C et al (2005) Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 23:7594–7603

    Article  PubMed  Google Scholar 

  7. Cheson BD, Bennett JM, Kantarjian H et al (2000) Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96:3671–3674

    PubMed  CAS  Google Scholar 

  8. Goodman C, Chan S, Collins P, Haught R, Chen YJ (2003) Ensuring blood safety and availability in the U.S.: technological advances, costs, and challenges to payment—final report. Transfusion 43:3S–46S

    Article  PubMed  Google Scholar 

  9. Pitocco C, Sexton TR (2005) Alleviating blood shortages in a resource-constrained environment. Transfusion 45:1118–1126

    Article  PubMed  CAS  Google Scholar 

  10. Blood collection and transfusion in the United States in 1999. Available from URL: http://www.sabm.org/news/detail.php?id=193. Accessed 11 Jul 2007

  11. Italian Cooperative Study Group For rHuEpo in Myelodysplastic Syndromes (1998) A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Br J Haematol 103:1070–1074

    Article  Google Scholar 

  12. Terpos E, Mougiou A, Kouraklis A et al (2002) Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haemato 118:174–180

    Article  CAS  Google Scholar 

  13. Casadevall N, Durieux P, Dubois S et al (2004) Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood 104:321–327

    Article  PubMed  CAS  Google Scholar 

  14. Thompson JA, Gilliland DG, Prchal JT et al (2000) Effect of recombinant human erythropoietin combined with granulocyte/macrophage colony-stimulating factor in the treatment of patients with myelodysplastic syndrome. GM/EPO MDS Study Group. Blood 95:1175–1179

    PubMed  CAS  Google Scholar 

  15. Stenke L, Wallvik J, Celsing F, Hast R (1993) Prediction of response to treatment with human recombinant erythropoietin in myelodysplastic syndromes. Leukemia 7:1324–1327

    PubMed  CAS  Google Scholar 

  16. Hellstrom-Lindberg E (1995) Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol 89:67–71

    PubMed  CAS  Google Scholar 

  17. Di Raimondo F, Longo G, Cacciola EJR et al (1996) A good response rate to recombinant erythropoietin alone may be expected in selected myelodysplastic patients. A preliminary clinical study. Eur J Haematol 56:7–11

    Article  PubMed  CAS  Google Scholar 

  18. Musto P, Lanza F, Balleari E et al (2004) Darbepoetin alfa for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol 128:204–209

    Article  CAS  Google Scholar 

  19. Patton JF, Sullivan T, Mun Y, Reeves T, Rossi G, Wallace JF (2005) A retrospective cohort study to assess the impact of therapeutic substitution of darbepoetin alfa for epoetin alfa in anemic patients with myelodysplastic syndrome. J Support Oncol 3:419–426

    PubMed  CAS  Google Scholar 

  20. Mannone L, Gardin C, Quarre MC et al (2006) High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 133:513–519

    Article  PubMed  CAS  Google Scholar 

  21. Cheson DB, Greenberg PL, Bennett JM et al (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108:419–425

    Article  PubMed  CAS  Google Scholar 

  22. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  PubMed  CAS  Google Scholar 

  23. Stasi R, Brunetti M, Bussa S et al (1997) Response to recombinant human erythropoietin in patients with myelodysplastic syndromes. Clin Cancer Res 3:733–739

    PubMed  CAS  Google Scholar 

  24. Rigolin GM, Porta MD, Bigoni R et al (2002) rHuEpo administration in patients with low-risk myelodysplastic syndromes: evaluation of erythroid precursors response by fluorescence in situ hybridisation on May–Grunwald–Giemsa-stained bone marrow samples. Br J Haematol 119:652–659

    Article  PubMed  CAS  Google Scholar 

  25. Clavio M, Nobili F, Balleari E et al (2004) Quality of life and brain function following high-dose recombinant human erythropoietin in low-risk myelodysplastic syndromes: a preliminary report. Eur J Haemaol 72:113–120

    Article  CAS  Google Scholar 

  26. Mele G, Musto C, Vigliotti ML et al (2004) High-dose of epoetin alfa in patients with low-risk myelodysplastic syndromes (MDS): a single institution experience. Blood 140(11) [Abstract]

  27. Aloe Spiriti MA, Latagliata R, Niscola P et al (2005) Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome. Ann Hematol 84:167–176

    Article  CAS  Google Scholar 

  28. Stein RS, Abels RI, Krantz SB (1991) Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes. Blood 78(7):1658–1663

    Google Scholar 

  29. Adamson JW, Schuster M, Allen S, Haley NR (1992) Effectiveness of recombinant human erythropoietin therapy in myelodysplastic syndromes. Acta Haematol 87(Suppl 1):20–24

    Article  PubMed  Google Scholar 

  30. Rafanelli R, Grossi A, Longo G, Vannucchi AM, Bacci R, Ferrini PR (1992) Recombinant human erythropoietin for treatment of myelodysplastic syndromes. Leukemia 6(4):323–327

    PubMed  CAS  Google Scholar 

  31. Verhoef GEG, Zachée A, Demuynck H et al (1992) Recombinant human erythropoietin for the treatment of anemia in the myelodysplastic syndromes: a clinical and erythrokinetic assessment. Ann Hematol 64:16–21

    Article  PubMed  CAS  Google Scholar 

  32. Aloe Spiriti MA, Petti MC, Latagliata R et al (1993) Is recombinant human erythropoietin treatment in myelodysplastic syndromes worthwhile? Leuk Lymphoma 9:79–83

    Article  PubMed  CAS  Google Scholar 

  33. Goy A, Belanger C, Casadevall N et al (1993) High doses of intravenous recombinant erythropoietin for the treatment of anaemia in myelodysplastic syndromes. Br J Haematol 84:232–237

    Article  PubMed  CAS  Google Scholar 

  34. Ludwig H, Fritz E, Leitgeb C et al (1993) Erythropoietin treatment for chronic anemia of selected hematological malignancies and solid tumors. Ann Oncol 4:161–167

    PubMed  CAS  Google Scholar 

  35. Zeigler ZR, Jones D, Rosenfeld CS, Shadduck RK (1993) Recombinant human erythropoietin (rHuEPO) for treatment of myelodysplastic syndromes. Stem Cells 11:49–55

    Article  PubMed  CAS  Google Scholar 

  36. Marques da Costa R (1994) Current use of recombinant human erythropoietin (r-huEPO) in the management of symptomatic anaemia in patients with myelodysplastic syndromes (MDS). Sangre 39:105–110

    PubMed  CAS  Google Scholar 

  37. Rose EH, Abels RI, Nelson RA, McCullough DM, Lessin L (1995) The use of r-HuEpo in the treatment of anaemia related to myelodysplasia (MDS). Br J Haematol 89:831–837

    Article  PubMed  CAS  Google Scholar 

  38. Wallvik J, Stenke L, Bernell P, Nordahl G, Hippe E, Hast R (2002) Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPI treatment in patients with myelodysplastic syndromes. Eur J Haematol 68:180–186

    Article  PubMed  CAS  Google Scholar 

  39. Tsabouri SE, Georgiou I, Katsaraki A, Bourantas KL (2004) Treatment of MDS patients with recombinant human erythropoietin and the role of GSTs. J Exp Clin Cancer Res 23:417–424

    PubMed  CAS  Google Scholar 

  40. Gotlib J, Quesada S, Bhamidipati J et al (2004) Phase II trial of darbepoetin alfa in myelodysplastic syndrome (MDS): preliminary efficacy, safety, and in vitro results. Blood 104(11) [Abstract no. 4737]

  41. Oliva EN, Ronco F, Danova M et al (2004) Darbepoetin efficacy in myelodysplastic syndrome. Blood 104(11) [Abstract no. 4704]

  42. Giraldo P, Nomdedeu B, Loscertales J et al (2005) Darbepoetin alfa for the treatment of anemia in patients with myelodysplastic syndrome. Blood 106(11) [Abstract no. 2542]

  43. Stasi R, Abruzzese E, Lanzetta G, Terzoli E, Amadori S (2005) Darbepoetin alfa for the treatment of anemic patients with low- and intermediate-1-risk myelodysplastic syndromes. Ann Oncol 16:1921–1927

    Article  PubMed  CAS  Google Scholar 

  44. Gabrilove J, Paquette R, Lyons R, et al (2006) Darbepoetin alfa for treating anemia in patients with low-risk myelodysplastic syndromes: Exploratory analysis of baseline predictors of response. J Clin Oncol 24(18S) [Abstract no. 6579 and poster presentation]

  45. Hellstrom-Lindberg E, Gulbradsen N, Lindberg G et al (2003) A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 120:1037–1046

    Article  PubMed  CAS  Google Scholar 

  46. Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E (2005) Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 106:803–811

    Article  PubMed  CAS  Google Scholar 

  47. Berlin J, Santanna J, Schmid CH, Szczech LA, Feldman H (2002) Individual patient- versus group-level data meta-regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head. Stat Med 21:171–187

    Article  Google Scholar 

  48. Epoetin alfa (ProcritÒ) product package insert. Available from URL: http://www.orthobiotech.com/common/prescribing_information/PROCRIT/PDF/ProcritBooklet.pdf. Accessed 11 Jul 2007

  49. Darbepoetin Alfa (AranespÒ) product package insert. Available from URL: http://www.aranesp.com/pdf/aranesp_PI.pdf. Accessed 11 Jul 2007

  50. Park S, Kelaidi C, Grabar SO, et al (2006) Prognostic factors and response duration in 419 MDS treated with erythropoietin±GCSF: The GFM experience. Blood 108(11). [Abstract no. 522]

  51. Jadersten M, Malcovati L, Dybedal I, et al (2006) Treatment with erythropoietin and G-CSF improves survival in MDS patients with low transfusion need. Blood 108(11). [Abstract no. 521]

  52. Musto P (2005) Recombinant erythropoietin and survival in myelodysplastic syndromes. Blood 106. [Abstract no. 2539]

  53. Golshayan AR, Jin T, Maciejewski J et al (2007) Efficacy of growth factors compared to other therapies for low-risk myelodysplastic syndromes. Br J Haematol 137:125–132

    Article  PubMed  CAS  Google Scholar 

  54. Malcovati L, Della Porta MG, Cazzola M (2006) Predicting survival and leukemic evolution in patients with myelodysplastic syndrome. Haematologica 91:1588–1590

    PubMed  Google Scholar 

  55. Armand P, Kim HT, Cutler CS et al (2007) Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 109:4586–4588

    Article  PubMed  CAS  Google Scholar 

  56. Oliva EN, Dimitrov BD, Benedetto F, D, Angelo A, Nobile F (2005) Hemoglobin level threshold for cardiac remodeling and quality of life in myelodysplastic syndrome. Leuk Res 29:1217–1219 Epub 2005 Apr 7

    Article  PubMed  CAS  Google Scholar 

  57. Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C (2005) Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci 1054:445–450

    Article  PubMed  Google Scholar 

  58. Gordeuk VR, McLaren GD, Samowitz W (1994) Etiologies, consequences, and treatment of iron overload. Crit Rev Clin Lab Sci 31:89–133

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Parts of this work were presented as a poster at the American Society of Clinical Oncology (ASCO) 2006 Annual Meeting and the American Society of Hematology (ASH) 2006 Annual Meeting and Exposition. Financial support for this study was provided by Ortho Biotech Clinical Affairs, LLC. Patrick Lefebvre and Mei Sheng Duh have received research grants from Ortho Biotech Clinical Affairs, LLC. Victor Moyo, Behin Yektashenas, and Suneel Mundle are employees of Ortho Biotech Clinical Affairs, LLC. The authors would like to thank Ahmed Bourezak and Sharon Buteau of Groupe d’analyse, Ltée for their assistance with the preparation of this manuscript.

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Authors and Affiliations

  1. Ortho Biotech Clinical Affairs, LLC, Bridgewater, NJ, USA

    Victor Moyo, Behin Yektashenas & Suneel Mundle

  2. Groupe d’analyse, Ltée, Montreal, QC, Canada

    Patrick Lefebvre

  3. Analysis Group, Inc., Boston, MA, USA

    Mei Sheng Duh

  4. Rush University Medical Center, Chicago, IL, USA

    Suneel Mundle

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  1. Victor Moyo
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Correspondence to Suneel Mundle.

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Moyo, V., Lefebvre, P., Duh, M.S. et al. Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis. Ann Hematol 87, 527–536 (2008). https://doi.org/10.1007/s00277-008-0450-7

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