Transforming growth factor (TGF)-beta ligand trapping agents can also produce erythroid improvements in lower-risk patients with MDS. A recent phase 2 study reported that approximately two-thirds of lower-risk patients with low transfusion burden and anemia experienced erythroid improvements with luspatercept, a novel TGF-beta inhibitor that will soon be available for individuals with lower-risk disease.

Treatment Options for Higher-Risk MDS

Hypomethylating agents (HMAs) such as azacitidine and decitabine are the mainstay of therapy for patients with higher-risk MDS. Several investigational agents are currently being studied in combination with HMAs in clinical trials, including lenalidomide, histone deacetylase inhibitors, pevonedistat, and sonidegib. A novel HMA, guadecitabine, is currently being evaluated in patients with various forms of AML and MDS in phase 1 and 2 trials.

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Allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative treatment for patients with MDS. However, the procedure is often associated with life-threatening complications, and the risk for relapse remains high in certain cases. As the technique continues to advance with enhanced molecular human leukocyte antigen-typing, improved supportive care and donor choice, and innovations in graft-versus-host disease prophylaxis, results may soon improve.

Other investigational therapies for higher-risk patients include IDH1 and IDH2 inhibitors, rigosertib, nivolumab and ipilimumab, and venetoclax combinations. At present, these agents are in various stages of clinical development.

Limited understanding of the molecular pathogenesis underlying MDS has impaired the development of novel therapeutic options. In addition, the genetic heterogeneity of the disorder warrants the development of therapies for specific subgroups of patients. As a result, enrolling patients into clinical trials is essential to continue developing novel therapies for MDS.

Expert Opinion: Barriers to Clinical Trial Enrollment

Sheng F Cai, MD, PhD, of the department of medicine at the Memorial Sloan Kettering Cancer Center in New York, New York, told Hematology Advisor, “I think it is essential for community hematologists to refer patients with MDS to major academic centers for consideration of clinical trials.”

He continued, “At our institution, we make every effort to enroll every patient [with MDS into a] clinical trial when possible, but we coordinate care with local hematologists so [that] clinical visits or transfusion appointments [do not always] need to be [completed] at our center. [We’ve found] this strikes the right balance for patients seeking to participate in a trial but also wanting the convenience of having [local] care with their community hematologist.”

Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


1. Germing U, Schroeder T, Kaivers J, et al. Novel therapies in low- and high-risk myelodysplastic syndrome [published online July 31, 2019]. Expert Rev Hematol. doi:10.1080/17474086.2019.1647778