Novel therapies in low- and high-risk myelodysplastic syndrome

ABSTRACT

Introduction: Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms with diverse clinical courses. The revised version of the international prognostic scoring system (IPSS-R) provides risk stratification into 5 different groups.

Areas covered: For lower-risk patients, red blood cell transfusions and iron chelation are the backbone of supportive care. In addition, erythropoiesis-stimulating agents (ESA) are used to ameliorate anemia. Lenalidomide is approved for the treatment of lower-risk patients with del(5q) who are transfusion-dependent. Patients with higher-risk disease should be offered allogeneic stem cell transplantation whenever possible. If they are unfit for transplantation or an appropriate donor cannot be found, hypomethylating agents may be used.

Expert opinion: New therapeutic options for lower-risk patients include thrombopoietin analogues, the TGF-beta family ligand trapping drug Luspatercept, and the telomerase inhibitor Imetelstat. Combinations of hypomethylating agents (HMA) with other compounds, and inhibitors of bcl2, such as venetoclax are being developed for higher-risk patients. Finally, hypomethylating agents in combination with donor lymphocytes may lead to long-term remission following molecular or hematological relapse after allogeneic SCT.

KEYWORDS:

• Myelodysplastic syndromes
• risk-adapted therapy
• hypomethylating agents
• erythropoiesis stimulating agents
• thrombopoiesis stimulating agents
• immunomodulating drugs
• TGF-beta ligand trapping
• bcl2 inhibition
• investigational drugs
• MRD monitoring

Article highlights

• There is no adequate standard of care for the majority of MDS patients

• TGF-beta ligand trapping agents will soon be available for lower-risk MDS

• TPO analogues will become available for lower-risk MDS with severe thrombocytopenia

• Imetelstat will probably be further developed for treatment of lower-risk MDS

• Venetoclax will become part of treatment strategies for higher-risk MDS

• Allogeneic stem cell transplantation will remain the only curative approach

• HMAs will play a major role in patients who relapse after allogeneic HSCT

• Molecular findings and monitoring of minimal residual disease will support treatment decisions in higher-risk MDS, especially after allogeneic HSCT

Declaration of interest

N Gatterman has served on advisory boards for and received lecture honoraria from Novartis. They have also received research support from Takeda and Alexion. U Germing has received speakers’ honoraria from Celgene, Novartis, Amgen, Janssen and Jazz Pharmaceuticals. They have also received institutional research support from Celgene and Novartis. T Shroeder has served on advisory boards for and received travel support and honoraria from Celgene and Janssen. They have also received research support from Celgene. J Kaivers has received travel support from Jazz Pharmaceuticals. A Kündgen has received travel expenses and honoraria from Takeda, as well as speakers’ honoraria from Otsuka and Novartis. G Kobbe has received research support from Celgene and Amgen, as well as travel support from Celgene, Amgen, Neovii, Takeda, Roche, Jazz Pharmaceutical, Pfizer, Biotest and Medac. T he authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has received research funding from Genetech for a study in MDS. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.