The MDS Beacon™

A Phase 3 study completed by the Eastern Cooperative Oncology Group shows that lower-risk myelodysplastic syndromes (MDS) patients with anemia benefit from erythropoietin (EPO) treatments plus supportive care to increase their red blood cell counts, compared to patients who receive supportive care alone. The benefits are even higher when EPO is combined with granulocyte colony-stimulating factor (G-CSF).

EPO belongs to the group of erythropoiesis stimulating agents (ESAs), which help to increase the red blood cell count in MDS patients who have MDS-related anemia. Sometimes when patients do not respond to EPO alone the drug is paired with another drug, G-CSF.

The study included 110 lower-risk MDS patients who were anemic. The patients were randomly placed in two different groups. One group received EPO with or without G-CSF plus supportive care, while the other group received supportive care alone.

After four months of treatment, 36 percent of the patients in the EPO group responded to treatment with an increased red blood cell count. Only 10 percent of patients in the supportive care group responded. Additionally, EPO reduced the need for red blood cell transfusions; 29 percent of the EPO group still required transfusions compared to 51 percent of the supportive care group.

For the patients who did not respond to EPO alone, 22 percent of these patients responded when G-CSF was added to their regimen. For patients who still did not respond, EPO doses were increased, and 50 percent of these patients responded. Overall, 47 percent of patients responded to EPO alone or in combination with G-CSF.

Although patients in the EPO group responded better to treatment than the supportive care group, survival rates for the two groups were similar. The EPO group survived on average 3.1 years, and the supportive care group survived 2.6 years.

However, patients with the MDS subtype refractory anemia with ring sideroblasts (RARS) had prolonged survival when treated with EPO. Also, MDS patients who responded to EPO treatment lived on average 5.5 years compared to non-responders who lived 2.3 years.

ESA treatments have been linked to increased risk of developing leukemia, such as acute myeloid leukemia (AML). This study shows that ESA treatments may be safer than previously thought.

Among the patients taking EPO, 7.5 percent developed AML, while 10.5 percent of patients in the supportive care only group developed AML. Although a larger percent of patients in the supportive care group developed AML, the difference between the two groups was not significant.

Dr. Peter Greenberg, Department of Hematology at Stanford University Cancer Center and lead author of the study, said, “These data do not support the concerns of increased risk of leukemic progression or other cancers in these patients.”

According to quality of life assessments, patients who responded to EPO treatment also experienced improved physical, emotional, and functional well-being as well as fatigue and overall quality of life.

This study does not investigate whether EPO in combination with Revlimid (lenalidomide), Vidaza (azacitidine) or Dacogen (decitabine) improves red blood cell count or reduces the need for transfusions.

“Studies evaluating [the implications of Revlimid, Vidaza, and Dacogen] are needed,” said Dr. Greenberg. “A trial assessing the impact of EPO for patients not responding to Revlimid is ongoing.” The Phase 3 clinical study of Revlimid with or without EPO is currently recruiting patients. Like EPO, Revlimid also reduces transfusion dependency.

Dr. David Steensma, a physician in the Department of Hematological Malignancies at the Dana-Farber Cancer Institute, said “I don’t think this study is especially informative,” commenting on the study’s design, small number of patients compared to other ESA studies, and the way in which they administered EPO. “However, it does show a response rate for ESAs in a general MDS population, and suggests that if there are positive or negative effects on survival from EPO in MDS, they are not huge.”

Despite the study’s failure to demonstrate prolonged survival rates for patients with MDS-related anemia, Steensma points out that the study does have importance.

“There is a role for studies of agents [like EPO] that can potentially make things more convenient for patients (e.g., fewer transfusions) or improve quality of life, even if they do not improve quantity of life,” said Steensma.

For more information, please see the full study in the journal Blood or David Steensma’s editorial.