Recent Advances in MDS and CML - Episode 11
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Clinical studies have explored several novel agents as treatments for patients with myelodysplastic syndromes (MDS), notes Elias J. Jabbour, MD. One such agent, rigosertib, was recently explored in a phase III trial in comparison with best supportive care following progression on hypomethylating agents (HMAs). Unfortunately, this study did not meet its primary endpoint of extension in overall survival.
The p38 MAP kinase inhibitor ARRY-614 has been explored for some time, and was recently reformulated for better kinetics, notes Rami S. Komrokji, MD. In a phase I study looking at the new formulation, responses were observed across all dose levels, including in patients who progressed on HMAs. In general, the side effects of the agent were tolerable, notes Komrokji.
Genome sequencing of MDS has highlighted the p53 pathway, which is being addressed through clinical trials using MDM2 inhibitors, notes Mark J. Levis, MD, PhD. Research has suggested that lenalidomide promotes p53 degradation by restoring MDM2 function in MDS with 5q deletions, offering a potential treatment options, adds Komrokji.
In addition to the exploration of novel agents, studies are examining the optimization of treatment with HMAs in MDS, notes Ruben A. Mesa, MD. These studies are examining different dosing and schedules, particularly in patients with RAEB-1 or RAEB-2 MDS using oral azacitidine.
In order to optimize treatment with decitabine, Jabbour administers the drug for only 3 days rather than 5 days. This lower dosing improves cytopenias associated with the drug, according to a phase II study. If this lower dosing is shown to be as effective, it could have a big impact on quality of life for patients, notes Levis.