High Response Rate to Epoetin Beta in Elderly Patients with Myelodysplasia (MDS): Results of a Prospective Study.

Background: Anemia of MDS is common in elderly patients. Recombinant Erythopoietin (EPO) alfa or beta, when used alone, improves anemia in 20 to 30 % of MDS in general population. In older patients with MDS, anemia is usually treated by transfusion supportive regimens. We report the results of a prospective study we conducted on the use of Epoetin Beta in anemic elderly patients with MDS. Patients and Treatment: Inclusion criteria were patient aged 75 years and over with MDS chronic anemia requiring transfusion or Hb < 10g/dl exclusion of other causes of anemia. Patients were treated with Epoetin beta 150 IU/ kg x 3/week during at least 8 weeks. In the absence of response, Epoetin beta dose was increased to 300 IU/ kg x 3/week and a new evaluation made after 8 weeks. Response was evaluated based on IWG criteria. In patients responding to Epoetin Beta, intervals between injections were adjusted to maintain Hb levels between 11 and 13g/dl. Seventy five patients (25 men, 50 women), median age 87.7 years (75 – 103), median creatinine clearance (CrCl) 36 ml/min (15 – 86) were included. They were classified as follows, 1 RARS, 54 RCMD, 17 RAEB1, 2 RAEB2, 1 5q- syndrome. There was not statistically significant correlation between pretreatment serum epo level and CrCl. Anemia was associated with neutropenia and/or thrombopenia in 19 patients and required transfusion in 44 patients. Karyotype was not performed in most of the patients. The median interval between onset of anemia and study treatment was 9 months (range 4 – 48). None of the patients had previously received EPO alfa or beta or Darbopoetin. Results: Sixty one of the 75 patients (81 %), including the patient with 5q- syndrome, had major erythroid haematological improvement (EHI) (transfusion independence in formerly transfused patients or rise of at least 2 g/dl of haemoglobin level in formerly non transfused patients). EHI was obtained with Epoetin beta lowest dose in 50/61 patients. No effect was seen on granulocytes and platelets. No side effects were observed. The response rates were 85 %, 68.5 % for RCMD and RAEB, respectively (p=NS). Pretreatment serum epo level was lower in responding patients than in non responding patients (median level 34 and 104 UI/l respectively, p< 0.05). Response rate was lower in transfused than in non transfused patients (72 and 93 % respectively, p <0.05). Similar response rates were found in patients with CrCl> or < to 40 ml/min (88 and 78 % respectively). Median response duration was not reached with a median follow up of 13 months (4 – 36). In responding patients, median adjusted Epoetin Beta dose was 190 IU/kg /week Conclusion: In elderly patients with MDS, EPO appears to be an effective treatment to correct anemia. Our results may be superior to those obtained in general population because of lowest pretreatment serum EPO levels and more frequent low risk MDS in elderly patients. In studies evaluating the effect of EPO on the anemia of MDS patients, response rates should be analyzed according to age especially if old and very old patients are included.