The role of hypomethylating agents in myelodysplastic syndrome: changing the management paradigm

Abstract

Modern treatment of myelodysplastic syndromes (MDS) with hypomethylating agents (HMAs) such as azacitidine (Vidaza) and decitabine (Dacogen) has changed the clinical landscape of these disorders. Novel drug combinations of HMAs with histone deacetylase inhibitor therapy may synergistically target different dysregulated molecular mechanisms within MDS clones. This article reviews current trial data concerning the use of the main HMAs in MDS patients where intensive chemotherapy and allogeneic stem cell transplantation is generally not an option. Collated data are presented of the clinical response outcomes, toxicity profiles and prognostic response criteria. Vidaza use in low-risk MDS cases, the selected place of allogeneic stem cell transplantation in older patients with significant comorbidity and the novel drug combination strategies for the future are discussed.

Keywords::

• decitabine
• high risk
• hypomethylating agents
• Int2
• myelodysplastic syndrome
• Vidaza

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The treatment with hypomethylating agents (HMAs), azacitidine (Vidaza) and decitabine (dacogen) has changed the landscape of Myelodysplastic syndromes (MDS). These drugs were the first medications that changed the natural history of the disease and improved outcome in older patients.

• • Treatment with HMAs can achieve hematologic response and even complete response in some high-risk MDS patients as well as delaying acute myeloid leukemia transformation, improving the quality of life and even prolonging life in the case of Vidaza.

• • Side effects of HMAs are tolerable with infections being the commonest complications occurring mostly in the first cycles of HMA therapy.

• • Vidaza treatment in older patients has improved overall survival resulting in a better quality of life as well as improvement in fatigue, dyspnea, physical functioning, positive affect and psychological distress.

• • Allogeneic stem cell transplantation (alloSCT) remains the only treatment able to cure MDS. HMAs are an effective bridge before alloSCT as well as maintenance therapy following alloSCT and as a part of salvage therapy with donor lymphocyte infusion.

• • The combination of Lenalidomide with Vidaza has been shown to be the most promising protocol, which appears to be both clinically active and safe.