Current therapy of myelodysplastic syndromes

Abstract

After being a neglected and poorly-understood disorder for many years, there has been a recent explosion of data regarding the complex pathogenesis of myelodysplastic syndromes (MDS). On the therapeutic front, the approval of azacitidine, decitabine, and lenalidomide in the last decade was a major breakthrough. Nonetheless, the responses to these agents are limited and most patients progress within 2 years. Allogeneic stem cell transplantation remains the only potentially curative therapy, but it is associated with significant toxicity and limited efficacy. Lack or loss of response after standard therapies is associated with dismal outcomes. Many unanswered questions remain regarding the optimal use of current therapies including patient selection, response prediction, therapy sequencing and combinations, and management of resistance. It is hoped that the improved understanding of the underpinnings of the complex mechanisms of pathogenesis will be translated into novel therapeutic approaches and better prognostic/predictive tools that would facilitate accurate risk-adaptive therapy.

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

“…TD anemia leading to secondary IO has been associated with adverse clinical outcomes and adverse effects on survival in patients with MDS [3][4][5][6]. Although no randomized prospective data examining the impact of ICT on survival in MDS have been reported to date, iron chelation therapy (ICT) is commonly prescribed to MDS patients with TD anemia, especially patients with lowerrisk (LR) MDS [7,8]. We have recently shown that ICT use in MDS has increased since the US FDA approval of the first oral chelator deferasirox (DFX) in 2005 [9].…”

Genome sequencing in myelodysplastic syndromes: can molecular mutations predict benefit from hypomethylating agent therapy?

“…Those with higher risk MDS (intermediate-2, high) have a median survival of <1 year, whereas those with lower risk MDS (intermediate-1, low) have a median survival of 3-8 years [3]. Prediction of outcomes is important in management as this impacts risk/benefit estimations for initiation of treatment, including hypomethylating agents (HMAs) and allogeneic hematopoietic cell transplantation (AlloHCT) [4]. Although HMAs improved outcomes for patients with higher risk MDS, not all patients benefit from this therapy and no reliable methods have been discovered to predict differential likelihood of benefit from HMAs.…”

Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB

“…Higher-risk MDS represents a significant therapeutic treatment challenge for any current chemotherapeutics because of poor responses to combination chemotherapy and shorter survival (25). Previous large studies using various induction regimens containing AraC in various combinations with idarubicin, fludarabine, topotecan, and cyclophosphamide demonstrated CR rates of ~40-60% for higher-risk MDS, median OS rate 10.4-13 months, and treatment-related early death 10-20% (2,3,26,27).…”