Combination Therapy for Patients with Myelodysplastic Syndromes
Name of the Trial
Phase III Randomized Study of Lenalidomide with Versus without Epoetin Alfa in Patients with Low- or Intermediate-1-Risk Myelodysplastic Syndromes and Symptomatic Anemia (ECOG-E2905). See the protocol summary.
Dr. Alan List, Eastern Cooperative Oncology Group
Why This Trial Is Important
Myelodysplastic syndromes (MDS) are a group of diseases in which the bone marrow does not make enough healthy blood cells. About one-third of MDS patients go on to develop leukemia. Decreased blood cell counts (cytopenias) are a hallmark of MDS, with anemia (low red blood cells) being the most common type of cytopenia.
MDS patients with symptomatic anemia may require blood transfusions to maintain safe red blood cell levels. Doctors often treat these patients with erythropoietin to help stimulate red blood cell production, but this treatment succeeds in only about 20 percent of patients. Currently there is no generally effective standard therapy for MDS patients who fail to respond to erythropoietin.
Some MDS patients with anemia who have not responded to erythropoietin do benefit from the drug lenalidomide (Revlimid). Specifically, patients with a gene deletion on chromosome 5q (5q31.1) are more likely to respond to lenalidomide therapy. Additionally, a recent pilot study suggests that lenalidomide may help sensitize patients without the 5q deletion to erythropoietin, leading to improved red blood cell production in those who had previously not responded to erythropoietin therapy.
In this trial, patients with MDS and symptomatic anemia who have a low or low-intermediate (also referred to as intermediate-1) risk of progression to leukemia will be treated with lenalidomide, and some will also receive a form of erythropoietin called epoetin alfa (Procrit). Patients with the 5q deletion will be assigned to the lenalidomide-only arm of the trial, while those without the deletion will be randomly assigned to receive either lenalidomide only or lenalidomide in combination with epoetin alfa. Patients in the lenalidomide-only arm may "cross over" to the combination therapy if they do not achieve a response or if they relapse after their initial treatment.
"This study should answer the question of whether or not combining erythropoietin with lenalidomide can help ameliorate anemia and reduce or eliminate the need for transfusions in a greater number of patients with MDS," said Dr. List. "If the combination is successful, this will be one of the first combination therapies ever employed for this disease.
"We are also hoping to answer a number of biological questions related to MDS, including whether there are biomarkers that can help us predict which patients will likely respond to combination therapy," he added.