Myelodysplastic syndromes: a review of therapeutic progress over the past 10 years

ABSTRACT

Introduction

Myelodysplastic syndromes (MDS) represent a range of bone marrow disorders, with patients affected by cytopenias and risk of progression to AML. There are limited therapeutic options available for patients, including hypomethylating agents (azacitidine/decitabine), growth factor support, lenalidomide, and allogeneic stem cell transplant.

Areas covered

This review provides an overview of the progress made over the past decade for emerging therapies for lower- and higher-risk MDS (MDS-HR). We also cover advances in prognostication, supportive care, and use of allogeneic SCT in MDS.

Expert opinion

While there have been no FDA-approved therapies for MDS in the past decade, we anticipate the approval of luspatercept based on results from the MEDALIST trial for patients with lower-risk MDS (MDS-LR) and ringed sideroblasts who have failed or are ineligible for erythropoiesis stimulating agents (ESAs). With growing knowledge of the biologic and molecular mechanisms underlying MDS, it is anticipated that new therapies will be approved in the coming years.

KEYWORDS:

• Myelodysplastic syndromes
• targeted therapies
• lenalidomide
• erythropoiesis stimulating agents
• hypomethylating agents

Article highlights

• Over the past decade, there has been great advancement in the prognostication of MDS, with the development of the revised international prognostic scoring system (IPSS-R) criteria, along with personalized online calculators.

• Despite several large trials, hypomethylating agents (HMAs) remain first-line treatment for MDS-HR. There are no consensus options following HMA failure in high-risk MDS. Similarly, options are limited following ESA failure in MDS-LR.

• Novel HMAs, including CC-486 (oral azacitidine), ASTX727 (oral decitabine + cytidine deaminase inhibitor), and guadecitabine are being evaluated in different MDS sub-populations.

• Luspatercept, an erythroid maturing agent/TGF-β ligand trap, was recently approved for the treatment of β-thalassemia and will likely be approved for patients with MDS-LR with ringed sideroblasts who have failed or are ineligible for ESA.

• Magrolimab (CD-47 antibody) and APR-246 are two agents which have activity in combination with azacitidine in patients with some of the highest-risk features including those with P53 mutations

Declaration of interest

S Navada has received research funding from Onconova Therapeutics Inc. 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.

Reviewer disclosures

A peer reviewer on this manuscript has received research funding from Celgene, and served on the advisory boards for Novartis and Janssen. Peer reviewers have no other relevant financial relationships or otherwise to disclose.