Treating the anemia of MDS with erythropoietin: Impact of higher dose compared to combination with G/GM-CSF

Abstract

7082 Background: Recombinant human erythropoietin (EPO) is extensively used to improve erythropoiesis and reduce transfusions in anemic MDS pts. The addition of G/GM-CSF to EPO alfa or beta has been associated with higher erythroid response (ER) rates vs. EPO alone. Studies suggest higher ER rates could be achieved with EPO monotherapy if higher initiation doses were used. To study this question a meta-analysis was performed on studies of MDS pts treated with EPO alfa or beta + G/GM-CSF. Methods: Data extraction was performed on studies from PubMed, ASCO and ASH proceedings from 1990–2006 in MDS pts treated with EPO (alfa or beta) ± G/GM-CSF. To allow for cross comparisons, only studies including IWG or IWG-like ER criteria were selected for analysis. Pooled estimates of ER rates were calculated using fixed-effect (F-E) meta-analysis methods. Results were stratified by: (i) EPO-alfa at standard doses, (ii) EPO- alfa at high doses, (iii) EPO-alfa + G/GM-CSF, and (iv) EPO-beta + G/GM-CSF. Results: From 39 studies identified, 19 met inclusion criteria. Most pts (>55%) had RA/RARS. Studies using EPO-alfa at standard doses showed comparable ER rates to studies using EPO- alfa + G/GM-CSF (49.0% vs. 50.6%; p=0.731) ( Table ). Among EPO-alfa studies, those using higher EPO doses had higher ER rates vs. studies using standard EPO doses (p<0.001) or EPO + G/GM-CSF combination (p=0.007). Overall ER rates were not available for studies using EPO- beta + G/GM-CSF, however, 52 pts (37.7%) had major ER, similar to that observed in all EPO-alfa monotherapy studies (195/589=33.1%). Conclusions: These findings suggest increasing EPO-alfa dose may have a greater impact on ER than addition of G/GM-CSF. Further validation is warranted. [Table: see text] [Table: see text]