Following in the footsteps of acute myeloid leukemia: are we witnessing the start of a therapeutic revolution for higher-risk myelodysplastic syndromes?

Abstract

For most patients with higher-risk myelodysplastic syndromes (HR-MDS) the hypomethylating agents (HMA) azacitidine and decitabine remain the mainstay of therapy. However, the prognosis mostly remains poor and aside from allogeneic hematopoietic stem cell transplantation no curative treatment options exist. Unlike acute myeloid leukemia, which has seen a dramatic expansion of available therapies recently, no new agents have been approved for MDS in the United States since 2006. However, various novel HMAs, HMA in combination with venetoclax, immune checkpoint inhibitors, and targeted therapies for genetically defined patient subgroups such as APR-246 or IDH inhibitors, have shown promising results in early stages of clinical testing. Furthermore, the wider availability of genetic testing is going to allow for a more individualized treatment of MDS patients. Herein, we review the current treatment approach for HR-MDS and discuss recent therapeutic advances and the implications of genetic testing on management of HR-MDS.

Keywords:

• Myelodysplastic syndrome
• MDS
• hypomethylating agent
• combination therapy
• immune checkpoint inhibition

Acknowledgements

AMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a NCI’s Cancer Clinical Investigator Team Leadership Award (CCITLA). Research reported in this publication was in part supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement

A.M.Z. received research funding (institutional) from Celgene, Acceleron, Abbvie, Novartis, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics. A.M.Z had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Jazz, Ariad, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, Trovagene, Ionis, Epizyme, and Takeda. A.M.Z received travel support for meetings from Pfizer, Novartis, and Trovagene. J.P.B. has no conflicts of interest to declare.

Additional information

Funding

This research was partly funded by the Dennis Cooper Hematology Young Investigator Award (AMZ) and was in part supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.