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Review
. 2021 Jan 25:13:645-657.
doi: 10.2147/CMAR.S240600. eCollection 2021.

Clinical Management of Anemia in Patients with Myelodysplastic Syndromes: An Update on Emerging Therapeutic Options

Russell Lewis  1 , Jan Philipp Bewersdorf  1 , Amer M Zeidan  1
Affiliations
Review

Clinical Management of Anemia in Patients with Myelodysplastic Syndromes: An Update on Emerging Therapeutic Options

Russell Lewis et al. Cancer Manag Res. .

Abstract

For the majority of patients with lower-risk myelodysplastic syndrome (LR-MDS), one of the primary clinical goals is to alleviate the symptoms associated with the resultant cytopenias and to minimize the transfusion burden. While supportive red blood cell (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, most patients either do not respond to ESAs or will eventually develop resistance. As such, there is a great need for further therapeutic options in the management of anemia related to MDS. Several additional therapeutics are now available in select patients with LR-MDS and symptomatic anemia including luspatercept, lenalidomide, and immunosuppressive therapy. Furthermore, several novel agents are currently in development to address this area of clinical need such as imetelstat and roxadustat. In this article, we review the currently available therapeutic options for symptomatic anemia in LR-MDS as well as review the therapeutic agents in development.

Keywords: clinical trials; erythropoiesis-stimulating agents; myelodysplastic syndrome; novel agents.

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Conflict of interest statement

A.M.Z. received research funding (institutional) from Celgene/BMS, AbbVie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff oncology, Incyte, Takeda, Novartis, Aprea, and ADC Therapeutics. A.M.Z participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Trovagene/Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, and Tyme. A.M.Z served on clinical trial committees for Novartis, AbbVie, Geron and Celgene/BMS. A.M.Z received travel support for meetings from Pfizer, Novartis, and Trovagene/Cardiff Oncology. None of these relationships were related to the development of this manuscript. R.L. and J.P.B. have no conflicts of interest.

Figures

Figure 1
Figure 1
Mechanism of action for select agents used or under investigation for the management of LR-MDS, Imetelstat directly inhibits telomerase, thus preventing telomerase from adding telomere repeat sequences to the 3ʹ-end of telomeres. Roxadustat inhibits HIF-PH, thus leading to decreased HIF-alpha degradation and increased HIF-alpha signaling. Luspatercept and similar erythropoiesis maturation agents (EMAs) act as a ligand trap which prevents TGF-beta activation and leads to decreased downstream SMAD2 and SMAD3 signaling. Lenalidomide has a complex mechanism of action; it has a direct antiproliferative effect via inhibition of CDC25C phosphatase which leads to cell cycle arrest; it also leads to ubiquitination of CK1a and IKZF1 which leads to apoptosis. Hypomethylating agents (HMA) lead to increased DNA methylation by causing degradation of DNA methyltransferase (DNMT). This leads to decreased inactivation of tumor suppressor genes.
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References

    1. Cazzola M. Myelodysplastic syndromes. N Engl J Med. 2020;383(14):1358–1374. doi:10.1056/NEJMra1904794 - DOI - PubMed
    1. Zeidan AM, Faltas B, Douglas Smith B, Gore S. Myelodysplastic syndromes: what do hospitalists need to know? J Hosp Med. 2013;8(6):351–357. doi:10.1002/jhm.2049 - DOI - PMC - PubMed
    1. Platzbecker U. Treatment of MDS. Blood. 2019;133(10):1096–1107. doi:10.1182/blood-2018-10-844696 - DOI - PubMed
    1. Nazha A, Sekeres MA, Gore SD, Zeidan AM. Molecular testing in myelodysplastic syndromes for the practicing oncologist: will the progress fulfill the promise? Oncologist. 2015;20(9):1069–1076. doi:10.1634/theoncologist.2015-0067 - DOI - PMC - PubMed
    1. Hong M, The HG. 2016 Revision to the world health organization classification of myelodysplastic syndromes. J Transl Int Med. 2017;5(3):139–143. doi:10.1515/jtim-2017-0002 - DOI - PMC - PubMed