Treatment of anemia with recombinant human erythropoietin (rHuEPO) alone is effective only in a small percentage of MDS patients. A meta-analysis of 205 patients with MDS showed that 16% responded to rHuEPO alone.Patients with a transfusion need of < 2 units per month and a serum erythropoietin concentration of < 500 U/l had a 74% response rate to combined erythropoietin/G-CSF compared to a response rate of 23% and 7% for those patients with a > 2 units per month transfusion need or serum erythropoietin concentration > 500 U/l or both of these risk factors, respectively. Recent randomized, placebo controlled, double-blind clinical trial of erythropoietin was reported in which the rHuEpo treated patients had a median survival of 17 months compared to a median survival of 11 months in the placebo treated patients.
Although FDA has not approved erutropoietin stimulaitng factors for MDS, several supportive guidelines have been published. The first was the Italian Society of Hematology in 2002, updated in 2004. A
The last updateon this topic the 2011 National Comprehensive Cancer Network guideline dedicates significant space too the evaluationand treatment of of MDS-related anemia. For symptomatic anemia, in IPSS low group, treatment is indicated by the level of endogenous EPO. If EPO < 500U/L, the treatment of choice is EPO-alpha, 40,000–60,000 U, 1–3 times weekly subcutaneously (s.c.), or darbepoetin, 150–300 μg weekly s.c. In cases of the presence of ringed sideroblasts or an absence of response, the addition of G-CSF, 1–2 μg/kg 1–3 times per week should be considered, as well as therapy with immunosuppressive or hypomethylating agents when endogenous EPO levels are >500 U/L.
Similar guidelines were published by the American Society of Hematology and the American Society of Clinical Oncology. Some guidelines, for example NCCN, recommend erytrhopoietin in IPSS Low disease and with erytropoietin levels below 500. The NCCN 2007 version of the guidelines added darbepoetin alfa (Aranesp®, Amgen) as a recommendation for anemic patients with low-intermediate risk MDS.
There are intriguing reports of MDS patients responding to long-acting darbepoetin (DAR) after being refractory to primary treatment with EPO. However, a recent meta-analysis compared treatment with EPO-α (n=589; 9 studies) versus DAR (n=389; 8 studies) and concluded that the response rates for both drugs were highly similar (58% and 59%, respectively, P=0.82) when assessed using unified response criteria as defined by the International Working Group (IWG) in 2000. Finally, the addition of G-CSF significantly enhanced the response rate compared with using EPO alone, as demonstrated in two randomized trials.
Jädersten M et al, Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol 2008;26:3607-3613
Musto P, et al, . Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes. Leuk Res 2010;34:981-985.
Alessandrino EP et al, Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica 2002;87:1286-1306.
Santini V,PE et al, . Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res 2010;34:1576-1588
I. Casadevall, P. Durieux, S. Dubois, F. Hemery, E. Lepage, M.-C. Quarre, G. Damaj, S. Giraudier, A. Guerci, G. Laurent, et al. 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, July 15, 2004; 104(2): 321 – 327.
Casadevall N, Durieux P, Dubois S, et al. 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. 2004;104:321-327.
Balleari E, Rossi E, Clavio M, et al. Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study. Ann Hematol. 2006;85:174-180.
Valeria Santini Clinical Use of Erythropoietic Stimulating Agents in Myelodysplastic Syndromes The Oncologist August 2011 vol. 16 suppl 3 35-42
Uwe Platzbecker, Treatment of MDS. Blood 2019 133:1096-1107