Incorporating novel agents in the treatment of myelodysplastic syndromes

Abstract 

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal stem cell (SC) disorders that mainly affect the elderly population. They are characterized by ineffective hematopoiesis which results in quantitative and qualitative cellular defects and high incidence of leukemic transformation. Recent advances in MDS research have led to the development of novel agents which appears to improve remission rates and survival when compared to best supportive care. Currently azacitidine, decitabine, and lenalidomide are approved by the US FDA for the treatment of MDS, while the activity of other novel agents such as histone deacetylase inhibitors, farnesyl-transferase inhibitors, novel thrombopoietic agents, and anti-angiogenesis molecules is under evaluation. Erythropoietin-stimulating agents, iron chelating therapy and thrombopoietin receptor ligands may also improve quality of life and possibly prolong survival in MDS patients. The only treatment modality that can achieve long-term survival is the allogeneic SC transplantation which is given only in selected patients. Moreover the heterogeneity of MDS and the patient's advanced age and co-morbidity are significant factors besides cytogenetics, IPSS and WPSS that should be taken into account during the decision-making process. Therefore clinicians should treat patients with MDS on an individual basis aiming the increase of the response rates and the decrease of treatment-associated toxicities. This can only be achieved through the better understanding of the MDS subgroups. If we can better define MDS subgroups we will be able to identify patients who will benefit from the incorporation of the novel agents, as monotherapy or in combinations regimens along with supportive care.

Keywords: Myelodysplastic syndrome, Hypomethylating agents, Immunomodulatory drugs, Azacitidine, Decitabine, Lenalidomide, Histone deacetylase inhibitors, Farnesyl-transferase inhibitors