Myelodysplastic syndromes, which are a diverse group of neoplasms that arise from hematopoietic stem cells, are characterized by ineffective hematopoiesis, leading to cytopenias such as anemia and neutropenia.
Myelodysplastic syndromes (MDS), which are a diverse group of neoplasms that arise from hematopoietic stem cells, are characterized by ineffective hematopoiesis, leading to cytopenias such as anemia and neutropenia.
In 2017, epoetin alfa, which is typically used in treating anemia associated with chemotherapy and chronic kidney disease, was approved in Europe to treat low- to intermediate-risk MDS (though this treatment approach is an off-label use in the United States). A new review of the literature describes the use of reference and biosimilar epoetin alfa to treat anemia in patients with MDS, and explores clinical guideline recommendations in Europe and the United States.
There have been 2 mechanisms proposed to explain why erythropoiesis-stimulating agents (ESAs) like epoetin alfa lead to response in approximately 50% of patients; the first is that ESAs may inhibit apoptosis, and the second is that they may stimulate polyclonal erythropoiesis.
ESAs have been widely used in lower-risk patients with MDS with anemia who do not have a del(5q) chromosome abnormality, leading to improved quality of life and avoidance of blood transfusions. Clinical trials and meta-analyses have supported this practice, and today, ESAs are generally accepted as first-line treatment for these patients. Limited data on ESAs in treating patients with del(5q) abnormalities, in whom lower response rates and shorter response durations have been reported, are available.
In addition to data from the EPOANE 3021 study of the reference epoetin alfa in patients with low-risk MDS, which met its primary end point of the proportion of patients achieving erythroid response up to week 24, the review also documents a study of biosimilar epoetin alfa, Binocrit, that demonstrated that the biosimilar was effective in this setting.
The retrospective, single-center, observational study assessed the efficacy of the biosimilar in low-risk patients with MDS and anemia, and it had a primary end point of erythroid response. Of 24 patients, 16 (66.7%) achieved an erythroid response and 15 (62.5%) became transfusion-independent. Two had a reduction in transfusion requirements, and 7 (29.1%) were nonresponders.
Currently, the European Society for Medical Oncology guidelines for managing anemia in cancer patients includes management of MDS. The guideline states that ESAs can be considered in patients with MDS who have symptomatic anemia and very low to intermediate levels of risk. Similarly, European LeukemiaNet guidelines recommend that low-risk patients with moderate to severe anemia can be considered for therapy with epoetin alfa or beta. The National Comprehensive Cancer Network (NCCN)’s guidelines recommend ESAs for symptomatic anemia in patients with lower-risk MDS without the del(5q) mutation. In those with the mutation, NCCN recommends lenalidomide, but it says that a trial of ESA can be undertaken.
Gascón P, Krendyukov A, Mathieson N, Aparo M. Epoetin alfa for the treatment of myelodysplastic syndrome-related anemia: a review of clinical data, clinical guidelines, and treatment protocols [published online March 27, 2019]. Leuk Res Rep. doi: 10.1016/j.leukres.2019.03.006.