Myelodysplastic Syndrome (MDS) Medication

Updated: Oct 01, 2022
  • Author: Emmanuel C Besa, MD; Chief Editor: Sara J Grethlein, MD, MBA, FACP  more...
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Medication Summary

Treatment of myelodysplastic syndrome (MDS) is based on the stage and mechanism of the disease that predominates the particular phase of the disease process. In the early phases, when increased bone marrow apoptosis results in ineffective hematopoiesis, retinoids and hematopoietic growth factors are indicated.

In late stages, with inevitable leukemic transformation, cytotoxic chemotherapy and bone marrow transplantation may be necessary. All of these modes of therapy are undergoing clinical trials to determine the overall benefit to quality of life and survival.

Cytotoxic chemotherapy is used in patients with MDS with increasing myeloblasts and those who have progressed to acute leukemia. The usual combination treatment is a cytarabine-anthracycline combination, which yields a response rate of 30-40% (high complication rate and morbidity in elderly patients).

New drug combinations using hematopoietic growth factors and new drugs, such as topotecan (Hycamtin), are yielding better response rates with lower morbidity. Aggressive chemotherapy may be indicated in small populations of elderly patients with good performance status and no associated serious medical comorbidity.

Patients with associated serious medical comorbidities should be treated with less aggressive agents such as azacitidine or arsenic trioxide (Trisenox), or they should be entered into a clinical trial. However, these are currently in the early experimental stages.


Retinoid-lilke Agents

Class Summary

Retinoids are the most active agents in MDS. Vitamin D-3 also has activity but is not of clinically significant value.

Isotretinoin or 13 cis-retinoic acid (Claravis, Amnesteem, Absorica, Zenatane, Myorisan)

This agent is the most active among retinoids. This form of therapy is not generally accepted as standard therapy.


Hematopoietic Growth Factors

Class Summary

Ineffective blood cell production is due to excess cellular apoptosis (programmed cell death) caused by activation of the Fas-Fas ligand. Hematopoietic growth factors are capable of reversing this process to some extent.

Epoetin alfa (Procrit, Epogen)

Epoetin alfa is a glycoprotein that stimulates red blood cell (RBC) production by stimulating division and maturation of committed RBC precursor cells. It is effective in 20-26% of MDS patients when administered alone and in as many as 48% of patients when combined with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF).

Darbepoetin (Aranesp)

Darbepoetin is an erythropoiesis-stimulating protein closely related to erythropoietin, a primary growth factor that is produced in the kidney and stimulates development of erythroid progenitor cells in bone marrow. This agent's mechanism of action is similar to that of endogenous erythropoietin, which interacts with stem cells to increase red cell production.

Darbepoetin differs from epoetin alfa (recombinant human erythropoietin) in containing 5 N-linked oligosaccharide chains, whereas epoetin alfa contains 3. Darbepoetin has a longer half-life than epoetin alfa, and may be administered weekly or biweekly.

Sargramostim (Leukine)

This GM-CSF stimulates division and maturation of earlier myeloid and macrophage precursor cells. It has been reported to increase granulocytes in 48-91% of patients with MDS.

Filgrastim (Neupogen, Granix)

This G-CSF stimulates division and maturation of granulocytes, mostly neutrophils, in 75-100% of MDS patients and seems to enhance erythroid response when given in combination with erythropoietin.


Antineoplastic Agent, Methylation Inhibitors

Class Summary

Demethylation agents are a ntineoplastics that exert anticancer effects by causing DNA demethylation or hypomethylation in abnormal hematopoietic bone marrow cells. These agents may restore normal function to the tumor suppressor genes responsible for regulating cell differentiation and growth.

Azacitidine (Vidaza)

Azacitidine is a pyrimidine nucleoside analogue of cytidine. It interferes with nucleic acid metabolism. It exerts antineoplastic effects by DNA hypomethylation and direct cytotoxicity on abnormal hematopoietic bone marrow cells. Nonproliferative cells are largely insensitive to azacitidine. This agent is approved by the US Food and Drug Administration for treatment of all 5 MDS subtypes.

Decitabine (Dacogen)

Decitabine is a hypomethylating agent believed to exert antineoplastic effects by incorporating into DNA and inhibiting methyltransferase, resulting in hypomethylation. Hypomethylation in neoplastic cells may restore normal function to genes that are critical for cellular control of differentiation and proliferation.

Decitabine is indicated for treatment of MDSs, including previously treated and untreated, de novo, and secondary MDSs of all French-American-British (FAB) subtypes (ie, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia) and International Prognostic Scoring System (IPSS) groups intermediate-1 risk, intermediate-2 risk, and high risk.



Class Summary

Immunomodulators elicit immunomodulatory, antiangiogenic properties, and inhibit proinflammatory cytokines.

Lenalidomide (Revlimid)

Lenalidomide is indicated for the transfusion-dependent MDS subtype of deletion 5q cytogenetic abnormality. This agent is structurally similar to thalidomide. It elicits immunomodulatory and antiangiogenic properties, inhibits proinflammatory cytokine secretion, and increases release of anti-inflammatory cytokines from peripheral blood mononuclear cells. The dose used in MDS is much lower than that used for multiple myeloma.


Antineoplastic agents, Miscellaneous

Class Summary

Agents in this class inhibit cell growth and proliferation.

Arsenic trioxide (Trisenox)

May cause DNA fragmentation and damage or degrade the fusion protein PML-RAR alpha. Use only in patients that have relapsed or are refractory to retinoid or anthracycline chemotherapy.


Erythroid Maturation Agents

Class Summary

These agents promote erythroid maturation by antagonizing inhibitors of late-stage erythropoiesis.

Luspatercept (Luspatercept-aamt, Reblozyl)

Indicated for treatment of anemia failing an ESA and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). It is not a substitute for RBC transfusions in patients who require immediate correction of anemia.