The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes

ABSTRACT

Introduction: Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndromes (MDS), but patients who relapse or are refractory have a poor prognosis with an estimated survival of 4–6 months. Rigosertib, a Ras mimetic that inhibits the phophoinositide 3-kinase and polo-like kinase pathways, has been tested in patients with higher-risk MDS following treatment with HMAs, where there are no approved second-line therapies.

Areas covered: This review will provide an overview of rigosertib, including safety and efficacy demonstrated in clinical trials.

Expert commentary: There is an urgent need for new treatment options for patients who have failed or progressed on HMAs. Rigosertib is currently undergoing testing as a single agent in certain subsets of higher-risk MDS patients as well as in combination with azacitidine, where preliminary data show efficacy in patients with de novo MDS as well as HMA failures.

KEYWORDS:

• Myelodysplastic syndromes
• rigosertib
• polo-like kinase
• phosphatidylinositol 3-kinase
• ON 0910.Na
• hypomethylating agents
• DNA methyltransferase inhibitors
• Ras-binding domain

Declaration of interest

LR Silverman and SC Navada receive research funding from Onconova Therapeutics. The authors have no other 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 apart from those disclosed.

Additional information

Funding

This paper was not funded.