Myelodysplastic syndrome (MDS) represents a group of conditions that result from blood-forming stem cells in the bone marrow failing to mature properly into healthy blood cells. As approximately 1 in 3 patients with MDS go on to develop acute myeloid leukemia (AML), MDS is considered a form of cancer.1 

The National Cancer Institute estimates that more than 10,000 new cases of MDS will be diagnosed annually, with increased risk among those treated with chemotherapy for other cancers.2 Diagnosis of MDS is uncommon in patients younger than 50 years; the condition typically affects those their 70s, with MDS risk increasing with age. The number of cases of MDS diagnosed annually is expected to increase as the average age of the US population rises.3

This article will focus on presenting information on all treatments for MDS currently approved by the US Food and Drug Administration (FDA), as well as other drugs recommended by MDS guidelines.

Management of Myelodysplastic Syndrome

Survival risk for patients with MDS can be broken down into 5 broad risk categories on the basis of variables such as bone marrow cytogenetics, bone marrow percentage of immature blast cells, and cytopenias, with corresponding risk of transformation into AML within 5 years.4 The median survival rate for patients with MDS can range from as high as 11.8 years in the very-low-risk category to as short as 9 months in those at high risk.5

Stem cell transplantation is currently the only MDS treatment with a realistic chance of cancer cure. However, many patients are ineligible for the procedure, and patients are typically required to be younger than 75 years and in otherwise good health for consideration.6 

Stem cell transplantation to treat MDS typically takes the form of allogeneic hematopoietic cell transplantation, in which the patient receives blood-forming stem cells from a compatible donor, often a close relative. Transplantation is usually reserved for patients with high-risk MDS or those who are at low risk but whose condition fails to respond to supportive care and pharmacotherapy.7

Currently the following pharmacotherapies have been approved by the FDA for the treatment of MDS: luspatercept, azacitidine, decitabine, decitabine-cedazuridine, and lenalidomide.8

Microscopic view of bone marrow biopsy specimen indicative of myelodysplastic syndrome.
Figure. Microscopic view of bone marrow biopsy specimen indicative of myelodysplastic syndrome. Credit: Getty Images.

Supportive Care

Treatment for MDS primarily centers on supportive or palliative care, which focuses on treating symptoms and improving quality of life for patients as opposed to treating MDS directly.7,9-11 Recommended supportive care includes regular assessments of blood counts and bone marrow specimens.12,13 

Blood transfusions are typically administered to treat symptoms of MDS, such as anemia, increased bleeding and bruising, and bacterial infections resulting from low white blood cell counts. Iron chelation therapy drugs such as deferasirox can be administered to prevent excess iron overload from repeated tranfusions.7

To treat anemia, recombinant human erythropoietin (rHu-EPO) and erythropoiesis-stimulating agents such as epoetin alfa and darbepoetin alfa may be administered to stimulate red blood cell production and reduce symptomatic anemia. If erythropoiesis-stimulating agents are not effective, erythroid-maturing agents such as luspatercept may also be prescribed.7

Colony-stimulating factors such as granulocyte colony-stimulating factor (G-CSF) may be given to restore white blood cell production and reduce the chance of infection. If bacterial infection does occur, various antibiotics may be used.7

If the previously mentioned treatments are insufficient for bleeding, antifibrinolytic agents such as aminocaproic acid may also be prescribed.7

For patients who require further treatment, pharmacologic options typically take the form of chemotherapy or immunosuppressive therapy.7 


Luspatercept is a recombinant fusion protein that promotes erythroid maturation by binding TGF-β superfamily ligands, diminishing Smad2/3 signaling, and enhancing pathways for late-stage erythropoiesis.14

Luspatercept is used to treat anemia in adult patients with beta thalassemia, and for anemia that fails to respond to erythropoiesis-stimulating agents in adult patients with very low- to intermediate-risk MDS with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).14

Dosage and Administration

In patients with anemia associated with MDS-RS or MDS/MPN-RS-T, the recommended starting dosage of luspatercept is 1 mg/kg once every 3 weeks via subcutaneous injection. The patient’s hemoglobin and transfusion record should be reviewed prior to administering each dose, and the dose should be titrated according to the patient’s response.14 

The dose of luspatercept may be increased if there is insufficient response to medication after at least 2 doses (6 weeks). If pre-dose hemoglobin levels exceed 11.5 g/dL in the absence of transfusions, the regimen should be paused and then resumed once hemoglobin levels drop below 11.5 g/dL. If hemoglobin levels increase too rapidly within 3 weeks in the absence of transfusions, the dose of luspatercept should be reduced. If the patient requires more than 17.5 mg/kg or less than 0.6 mg/kg of luspatercept, treatment should be discontinued.14

Treatment with luspatercept should be discontinued if grade 3 or 4 hypersensitivity reactions occur. If other grade 3 or 4 reactions occur, treatment should be paused until the adverse reaction(s) resolve to no more than grade 1 and then resumed at the next lower dose level.14

Monitoring Side Effects and Adverse Events 

Some of the most common (>10%) potential adverse reactions of luspatercept include the following14:

  • Fatigue
  • Headache
  • Musculoskeletal pain
  • Arthralgia
  • Dizziness/vertigo
  • Nausea
  • Diarrhea
  • Cough
  • Abdominal pain
  • Dyspnea
  • Hypersensitivity

The most common (>2%) grade 3 or 4 adverse reactions associated with luspatercept include fatigue, hypertension, syncope, and musculoskeletal pain.14

A potential side effect of luspatercept in patients with MDS is hypertension. Patients should have their blood pressure monitored during treatment, and antihypertensive treatment should be initiated, if necessary.14

As luspatercept is a therapeutic protein, there is a potential risk of immunogenicity.14 

Animal reproduction studies for luspatercept demonstrated adverse developmental outcomes including embryo-fetal mortality, alterations to growth, and structural abnormalities at exposures greater than the maximum recommended dose for humans. Based on these results, pregnant patients taking luspatercept should be advised of potential risk to the fetus, and patients who may become pregnant should be advised to use contraception during treatment and for at least 3 months after the last dose of luspatercept. Animal studies also suggest that luspatercept may affect female fertility.14

As luspatercept was detected in the milk of lactating rats, it is thus likely to be found in human milk. Because of the risk of serious adverse effects in breastfed infants and children, lactating patients are advised to avoid breastfeeding during treatment and for at least 3 months after the last dose of luspatercept.14

Drug-Drug Interactions

Coadministration of luspatercept with iron-chelating agents did not demonstrate any clinically significant differences in luspatercept pharmacokinetics.14


Chemotherapy involves the use of cytotoxic and other drugs to damage or kill cancerous cells. Chemotherapy agents typically act by interfering with cell division or by attacking various DNA synthesis and repair mechanisms.15 When treating patients with MDS, chemotherapy is administered systemically to destroy abnormal bone marrow stem cells, allowing normal cells to grow back.7

Chemotherapy is typically reserved for patients with MDS in low-risk categories who are deemed unlikely to respond well to immunosuppressive therapy or who experience significant symptoms, as well as for patients in high-risk categories to slow or prevent the progression of MDS into AML.7 

Patients who are candidates for allogeneic stem cell transplantation are typically placed on a chemotherapy regimen and possibly radiation therapy to condition them prior to the procedure. Further rounds of chemotherapy may be administered to patients who experience relapse after transplantation has taken place.7

Guidelines from the National Comprehensive Cancer Network (NCCN) as well as from other organizations typically recommend the hypomethylating agents azacitidine and decitabine as primary chemotherapy in patients experiencing clinically relevant symptoms such as thrombocytopenia, neutropenia, or increased marrow blasts, as well as in patients in high-risk MDS groups.7,9-11 High-risk patients may also be considered for treatment with standard chemotherapy regimens typically intended for AML, such as cytarabine, idarubicin, and daunorubicin, although these treatments are considered much less effective and are less frequently prescribed than hypomethylating agents.1


Azacitidine is a pyrimidine nucleoside analogue of cytidine that incorporates into RNA and DNA and binds covalently to the DNA methyltransferase 1 (DNMT1). This deactivates DNMT1, resulting in DNA hypomethylation and direct cytotoxicity to abnormal hematopoietic cells in the bone marrow.16 The cytotoxic effects of azacitidine target rapidly dividing cells such as cancer cells. Nonproliferative cells are largely insensitive to azacitidine. Azacitidine was the first drug approved by the FDA to treat MDS.17

Azacitidine is available in oral and injectable forms. It is usually prescribed for MDS, AML, and chronic myelomonocytic leukemia in adult patients, and for juvenile myelomonocytic leukemia in pediatric patients.16-18

Dosage and Administration

Patients are advised to premedicate for nausea and vomiting as well as undergo baseline laboratory testing including complete blood count (CBC), liver function tests, and serum creatinine prior to azacitidine treatment.16 

Azacitidine is contraindicated in patients with a known hypersensitivity to it or to mannitol, as well as patients with advanced malignant hepatic tumors or other hepatologic impairments.16

For patients with MDS, azacitidine is administered subcutaneously or intravenously (IV) at a starting dosage of 75 mg/m2 of body surface area daily for 7 days for all patients in the first treatment cycle, followed by 3 weeks of rest and then repeating the cycle every 4 weeks. Patients should be treated for a minimum of 4 to 6 cycles, with treatment continuing as long as the patient continues to benefit. If no improvement is seen after 2 cycles and if no toxicity occurs other than nausea and vomiting, then the dose may be increased to 100 mg/m2. The dose may require adjustment in response to nadir counts and hematologic response exceeding certain values.16

Clinicians are advised to not substitute IV azacitidine for the oral form, as the dosing regimens and pharmacokinetic parameters differ significantly between the 2 versions.16

Monitoring Side Effects and Adverse Events 

Some of the most common (>30%) potential adverse reactions associated with azacitidine administered subcutaneously include the following16

  • Cytopenias (anemia, thrombocytopenia, neutropenia, and leukopenia)
  • Vomiting
  • Pyrexia
  • Leukopenia
  • Diarrhea
  • Injection site erythema
  • Constipation
  • Ecchymosis
  • Nausea 
  • Vomiting

The most common additional adverse reactions resulting from IV administration of azacitidine also include the following16:

  • Petechiae
  • Rigors
  • Weakness 
  • Hypokalemia

As azacitidine causes anemia, neutropenia, and thrombocytopenia in adult patients with MDS, frequent monitoring of CBCs is advised to assess response and/or toxicity prior to each dosing cycle.16

Clinicians should use caution when considering treatment with azacitidine in patients with liver disease, as azacitidine has the potential to be fatally hepatotoxic in patients with severe pre-existing liver impairments. It is important to monitor liver chemistries in patients prior to initiation of therapy and with each cycle.16

As azacitidine and its metabolites are primarily excreted renally, patients with pre-existing renal impairment may be at risk for potential renal toxicity and should be closely monitored.16

Animal reproduction studies of azacitidine resulted in fetal deaths and abnormalities. Based on these results, patients of childbearing age are advised to avoid pregnancy while on azacitidine. Pregnant patients are to be informed of the potential hazard to the fetus, and patients who may father children are recommended to use contraception during treatment and 3 months after the last dose of azacitidine.16

There is risk of serious or fatal tumor lysis syndrome in patients with MDS who take azacitidine, even with coadministration of allopurinol as a preventive measure. Assessment of baseline risk in patients is recommended, including monitoring and treating, as appropriate.16

Clinical studies did not identify any overall differences in azacitidine effectiveness between patients 65 years of age and older and patients younger than 65. Likewise, the majority of adverse reactions were observed at similar frequencies in these 2 groups. As older patients are more likely to have decreased renal function, monitoring them for renal toxicity reactions is recommended.16

Drug-Drug Interactions

No formal clinical studies have been conducted on drug interactions with azacitidine.16


The mechanism of action of decitabine is similar to that of azacitidine.  Decitabine is a cytidine analogue that inhibits further DNA methylation, targeting abnormal bone marrow stem cells while leaving nonproliferating cells largely unaffected. The primary difference with azacitidine is that decitabine is phosphorylated by different kinases and is incorporated solely into DNA.19

Decitabine is administered via IV to treat MDS in adult patients.20

Dosage and Administration

Patients are advised to premedicate for nausea with antiemetics and to undergo baseline laboratory testing including CBC with platelets, serum hepatic panel, and serum creatinine prior to initiation of decitabine treatment.20

Decitabine is typically administered at a dosage of 15 mg/m2 via continuous IV infusion over 3 hours every 8 hours for 3 days, repeating the cycle every 6 weeks for a minimum of 4 cycles, with treatment continuing as long as the patient experiences benefit. An alternative regimen is to administer decitabine at a dosage of 20 mg/m2 via continuous IV infusion over 1 hour daily for 5 days.20

Monitoring Side Effects and Adverse Events 

The most common (>50%) adverse reactions associated with decitabine include20:

  • Cytopenias (neutropenia, thrombocytopenia, and anemia)
  • Pyrexia

Other common adverse reactions associated with decitabine include20:

  • Fatigue
  • Nausea
  • Coughing
  • Diarrhea
  • Constipation
  • Petechiae
  • Hyperglycemia

The most serious common side effect of decitabine treatment is myelosuppression, which may become serious or fatal in some patients. Myelosuppression is the most frequent cause of dose discontinuation, delay, and reduction in decitabine treatment. To minimize harm from decitabine side effects, CBCs with platelets should be assessed at baseline prior to each cycle, and response and toxicity should be monitored regularly.20

Myelosuppression and other adverse reactions associated with decitabine that most typically require clinical intervention include20

  • Dose discontinuation (thrombocytopenia, neutropenia, pneumonia, Mycobacterium avium complex infection, cardiorespiratory arrest, increased blood bilirubin, intracranial hemorrhage, and abnormal liver function tests)
  • Dose delay (neutropenia, pulmonary edema, atrial fibrillation, central line infection, and febrile neutropenia)
  • Dose reduction (neutropenia, thrombocytopenia, anemia, lethargy, edema, tachycardia, depression, and pharyngitis)

If hematologic toxicity occurs, the next cycle of decitabine therapy should be delayed for up to 2 weeks and the dose temporarily reduced to 11 mg/m2 every 8 hours (33 mg/m2/d, 99 mg/m2/cycle) upon restarting therapy. If certain nonhematologic toxicities occur (serum creatinine ≥2 mg/dL, alanine aminotransferase and total bilirubin levels greater than or equal to the upper limit of normal, and active or uncontrolled infection), treatment should be delayed and not resumed until the toxicities resolve.20 

Human data, animal studies, and its mechanism of action indicate that decitabine has teratogenic, fetotoxic, and embryotoxic effects. Patients of childbearing age are advised to avoid pregnancy while undergoing treatment with decitabine and to be tested for an existing pregnancy, while patients who are already pregnant should be informed of potential hazards to the fetus.20

Although there are no clinical data available on the presence of decitabine or its metabolites in human milk, due to the potential for serious decitabine-related adverse reactions in breastfed infants and children, lactating patients are advised to avoid breastfeeding during treatment and for at least 1 week after the last dose of decitabine.20

No clinical data currently exist on the use of decitabine in patients with hepatic or renal impairment; however, frequently monitoring for excessive toxicity is recommended.20

Clinical studies did not identify any overall differences in decitabine safety or effectiveness between patients 65 years of age and older and patients younger than 65, although greater sensitivity in older patients cannot be ruled out.20

Drug-Drug Interactions

No formal clinical studies have been conducted to evaluate drug interactions with decitabine, although in vitro studies in human liver microsomes suggest that decitabine is unlikely to inhibit or induce or serve as a substrate for cytochrome P450 enzymes.20


An alternate, orally administered formulation of decitabine combines it with the cytidine deaminase (CDA) inhibitor cedazuridine, which inhibits degradation of decitabine in the gut and liver, increasing systemic exposure.21 This tablet formulation allows the drug to be taken at home for greater patient convenience.22

Dosage and Administration

Patients are advised to premedicate with antiemetics to minimize nausea and vomiting. Baseline CBC should be obtained prior to initiating treatment with decitabine-cedazuridine and before each cycle.21

The recommended dosage of decitabine-cedazuridine is 1 tablet (containing decitabine 35 mg and cedazuridine 100 mg) taken orally once daily for 5 days in a row, repeating every 4 weeks for a minimum of 4 cycles or until disease progression or unacceptable toxicity. Patients should take the medication at the same time each day and avoid consuming food 2 hours before and after each dose.21

Orally administered decitabine-cedazuridine should not be substituted for IV decitabine within a cycle.21

Monitoring Side Effects and Adverse Events  

Common (≥20%) adverse reactions associated with combined decitabine-cedazuridine include the following21:

  • Fatigue
  • Constipation
  • Hemorrhage
  • Myalgia
  • Mucositis
  • Arthralgia
  • Nausea
  • Dyspnea
  • Diarrhea
  • Rash
  • Dizziness
  • Febrile neutropenia
  • Edema
  • Headache
  • Cough
  • Decreased appetite
  • Upper respiratory infection
  • Pneumonia
  • Elevated transaminase levels

The most common grade 3 or 4 laboratory abnormalities (≥ 50%) associated with decitabine-cedazuridine include the following21:

  • Decreased leukocytes
  • Decreased platelet count
  • Decreased neutrophil count
  • Decreased hemoglobin

Serious adverse reactions — such as febrile neutropenia (30%), pneumonia (14%), and sepsis (13%) — occurred in 68% of patients who received decitabine-cedazuridine in clinical trials. Fatal adverse reactions such as sepsis and respiratory failure occurred in 6% of patients. Adverse reactions requiring permanent dose discontinuation were reported in 5% of patients, while adverse reactions requiring dose reductions or interruptions occurred in 19% and 41% of patients, respectively.21

If myelosuppression occurs, the next cycle of decitabine-cedazuridine should be delayed and the patient’s blood count monitored. If hematologic recovery occurs within 2 weeks of achieving remission, decitabine-cedazuridine should be continued at the same dose. If hematologic recovery does not occur within 2 weeks of achieving remission, decitabine-cedazuridine should be delayed for up to 2 additional weeks and then resumed at a reduced dose of 1 tablet orally once daily on days 2 through 4.  Further dose reductions of 1 tablet orally once daily on days 1 through 3 and 1 tablet orally once daily on days 1, 3, and 5 can be considered.21

As with IV-administered decitabine, patients of childbearing age who are taking decitabine-cedazuridine are advised to avoid pregnancy. Pregnant patients should be informed of potential hazards to the fetus. Male patients are advised to use effective contraception during treatment and 3 months after the last dose of decitabine-cedazuridine.21

Due to the potential for serious decitabine-related adverse reactions in a breastfed infant or child, lactating patients are advised to avoid breastfeeding during treatment and for at least 2 weeks after the last dose of decitabine.21

Animal studies on decitabine and cedazuridine suggest that the combination therapy may cause impaired fertility in humans, the reversibility of which is unknown.21

Clinical studies did not demonstrate any overall differences in effectiveness in decitabine-cedazuridine between patients 65 years of age and older and patients younger than 65.21 

Modification of the decitabine-cedazuridine dosage is not recommended for patients with mild or moderate renal impairment; however, due to the potential for increased adverse reactions, frequent monitoring is recommended for patients with moderate renal impairment. Effects of decitabine-cedazuridine are unknown for patients with more severe renal impairment.21

Drug-Drug Interactions

As cedazuridine inhibits the CDA enzyme, coadministration of decitabine-cedazuridine with drugs that are metabolized by CDA should be avoided, as it may lead to increased systemic exposure and possibly increased toxicity of these drugs.21

Clinical studies reveal that coadministration of decitabine-cedazuridine with proton pump inhibitors had no clinically meaningful effect on exposure to either drug.21

Immune Treatments

Immunosuppressive therapy involves the use of drugs to suppress or weaken the patient’s immune system activity. Immunosuppressive therapy is typically prescribed to patients with lower-risk MDS who experience symptomatic cytopenias as a result of T-cell inhibition of hematopoiesis, suggesting an autoimmune component to their condition.23

The NCCN recommends immunosuppressive therapy for patients aged 60 years and younger with 5% or fewer marrow blasts and MDS with serum erythropoietin levels greater than 500 mU/mL. Antithymocyte globulin, cyclosporine, and eltrombopag, which are typically used to treat aplastic anemia, are offered by the NCCN as immunosuppressive treatments for MDS.7

The immunomodulating drug lenalidomide, which is used to increase hemoglobin levels, is also used to treat a subset of MDS patients with a partial deletion in chromosome 5 (MDS-del[5q]) .7 


Lenalidomide is an orally available thalidomide analogue and immunomodulator. It is typically used to treat patients experiencing symptomatic anemia in low- or intermediate-risk cases of MDS, particularly MDS with the aforementioned partial deletion in chromosome 5 (MDS-del[5q]) for which other treatments are inadequate. Taking lenalidomide may reduce or delay the need for blood transfusions.7

The mechanism of action of lenalidomide is complex, combining direct antiproliferative and proapoptotic effects on MDS hematopoietic cells with modulatory effects on the bone marrow immune microenvironment. This includes the promotion of T-cell proliferation and targeting of MDS cells and anti-inflammatory effects to counteract cytopenias.24

In addition to MDS, lenalidomide is typically used to treat adult patients with multiple myeloma, mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma.24 

Dosage and Administration

Lenalidomide is administered as an oral capsule in 2.5-mg, 5-mg, 10-mg, 15-mg, 20-mg, and 25-mg doses.24

As  lenalidomide is an analogue of thalidomide, a teratogen known to cause severe and life-threatening birth defects, it is contraindicated for patients who are pregnant or may become pregnant, or patients who may father children.24 Patients who become pregnant during the course of lenalidomide treatment are to immediately discontinue using the drug. Lenalidomide should not be used in patients who have experienced a severe hypersensitivity to the agent.24

Among patients taking lenalidomide for MDS-del(5q), weekly CBC monitoring for the first 8 weeks of therapy and at least monthly thereafter is recommended. Treatment should begin with an initial lenalidomide dosage of 10 mg once daily taken orally at about the same time each day with or without food. Patients are advised to continue or modify treatment based on clinical and laboratory findings, or until disease progression or unacceptable toxicity.24

Hematologic toxicities, particularly thrombocytopenia or neutropenia, may require interruption in treatment until the patient’s condition recovers, followed by resumption of treatment at a lower dose depending on how quickly the toxicities develop after treatment initiation and change in platelet count from baseline values.24

For other grade 3 or 4 toxicities determined to be associated with lenalidomide treatment, clinicians are advised to pause treatment and then restart at their discretion at the next lower dose following resolution of the toxicity to grade 2 or lower.24

When treating MDS in patients with renal impairment, the recommended dose and timing of the dose should be adjusted according to the patient’s creatine clearance using the Cockcroft-Gault equation. Lenalidomide 5 mg is recommended for patients with a creatinine clearance of 30 to 60 mL/min, and lenalidomide 2.5 mg is recommended for patients with a creatinine clearance below 30 mL/min. For patients requiring dialysis, lenalidomide should be administered after dialysis treatment on dialysis days.24 

Monitoring Side Effects and Adverse Events 

The most common (>15%) adverse reactions reported in patients taking lenalidomide to treat MDS include24

  • Cytopenias (thrombocytopenia and neutropenia)
  • Diarrhea
  • Pruritus
  • Rash
  • Fatigue
  • Constipation
  • Nausea
  • Nasopharyngitis
  • Arthralgia
  • Pyrexia 
  • Back pain
  • Peripheral edema
  • Cough
  • Dizziness
  • Headache
  • Muscle cramp
  • Dyspnea
  • Pharyngitis
  • Epistaxis

Lenalidomide may cause significant thrombocytopenia and neutropenia over the course of treatment. In clinical studies, as many as 80% of patients with MDS-del(5q) required a delay/reduction in lenalidomide dose over the course of treatment, and 34% required a second dose delay/reduction.24

Other serious and potentially fatal side effects associated with lenalidomide in patients with MDS include the development of secondary primary malignancies, hepatotoxicity, severe skin and allergic reactions, and tumor lysis syndrome.24 

Animal reproduction studies for lenalidomide revealed thalidomide-type limb defects in monkey offspring. Patients who are pregnant or who may become pregnant while using lenalidomide must be warned of the risk to the fetus. Screening, regular testing, and maintaining effective contraceptive measures against pregnancy in patients taking lenalidomide are of extremely high priority. If a patient misses a period or experiences any abnormality in menstrual bleeding, lenalidomide treatment must be discontinued while the patient undergoes evaluation for pregnancy.24

Male patients taking lenalidomide are likewise required to use contraceptive condoms during sexual contact with partners who may become pregnant and may not donate sperm while undergoing treatment.24

Although are no data exist on the presence of lenalidomide or its metabolites in human milk, patients undergoing treatment with lenalidomide are advised not to breastfeed during treatment.24

Of the patients in clinical trials taking lenalidomide for MDS-del(5q), the frequency of serious adverse reactions, including those severe enough for the patient to discontinue the study, was greater in patients older than 65 years compared with younger patients. As many as 80% of patients in clinical trials also experienced grade 3 or 4 hematologic toxicity.24

Drug-Drug Interactions

Plasma concentrations of digoxin may be elevated with coadministration of lenalidomide. Concomitant use of erythropoietin-stimulating agents or estrogen-containing therapies with lenalidomide may increase the risk of thrombosis.24

Myelodysplastic Syndrome Treatment Guidelines

The following guidelines are available to assist clinicians in managing patients with MDS: 


  1. About myelodysplastic syndromes. American Cancer Society. Updated January 22, 2018. Accessed June 13, 2023.
  2. Aster JC, Stone RM. Clinical manifestations, diagnosis, and classification of myelodysplastic syndromes (MDS). UpToDate. Updated March 24, 2023. Accessed June 13, 2023.
  3. Surveillance, Epidemiology, and End Results Program. SEER cancer statistics review, 1975-2014, National Cancer Institute. Updated April 2, 2018. Accessed June 13, 2023. 
  4. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465. doi:10.1182/blood-2012-03-420489
  5. Della Porta MG, Tuechler H, Malcovati L, et al. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia. 2015;29(7):1502-1513. doi:10.1038/leu.2015.55
  6. Treating myelodysplastic syndromes. American Cancer Society. Updated January 22, 2018. Accessed June 13, 2023. 
  7. NCCN guidelines for patients: myelodysplastic syndromes. National Comprehensive Cancer Network. Updated August 15, 2022. Accessed June 18, 2023.
  8. Saygin C, Carraway HE. Current and emerging strategies for management of myelodysplastic syndromes. Blood Rev. 2021;48:100791. doi:10.1016/j.blre.2020.100791
  9. Malcovati L, Hellström-Lindberg E, Bowen D, et al; European Leukemia Net. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943-2964. doi:10.1182/blood-2013-03-492884
  10. Fenaux P, Haase D, Santini V, Sanz GF, Platzbecker U, Mey U; ESMO Guidelines Committee. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(2):142-156. doi:10.1016/j.annonc.2020.11.002 
  11. Killick SB, Ingram W, Culligan D, et al. British Society for Haematology guidelines for the management of adult myelodysplastic syndromes. Br J Haematol. 2021;194(2):267-281. doi:10.1111/bjh.17612
  12. Tricot GJ, Lauer RC, Appelbaum FR, Jansen J, Hoffman R. Management of the myelodysplastic syndromes. Semin Oncol. 1987;14(4):444-453.
  13. Boogaerts MA. Progress in the therapy of myelodysplastic syndromes. Blut. 1989;58(6):265-270.
  14. Reblozyl®. Prescribing Information. US Food and Drug Administration. Updated April 2020. Accessed June 14, 2023.
  15. Types of chemotherapy. MedlinePlus. Updated October 28, 2021. Accessed May 8, 2023.
  16. Vidaza. Prescribing Information. US Food and Drug Administration. Updated May 2022. Accessed June 14, 2023.
  17. Kaminskas E, Farrell AT, Wang Y-C, Sridhara R, Pazdur R. FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005;10(3):176-182. doi:10.1634/theoncologist.10-3-176
  18. Azacitidine (Vidaza, Onureg). Cancer Research UK. Updated January 23, 2023. Accessed June 14, 2023.
  19. Hollenbach PW, Nguyen AN, Brady H, et al. A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One. 2010;5(2):e9001.   doi:10.1371/journal.pone.0009001
  20. Dacogen®. Prescribing Information.  US Food and Drug Administration. Updated December 2018. Accessed June 14, 2023.
  21. Inqovi®. US Food and Drug Administration. Updated July 2020. Accessed June 14, 2023. 
  22. FDA approves new therapy for myelodysplastic syndromes (MDS) that can be taken at home. News release. US Food and Drug Administration; July 07, 2020. Accessed June 14, 2023.
  23. Parikh A, Olnes MJ, Barrett AJ. Immunomodulatory treatment of myelodysplastic syndromes: antithymocyte globulin, cyclosporine, and alemtuzumab. Semin Hematol. 2012;49(4):304-311.  doi:10.1053%2Fj.seminhematol.2012.07.004
  24. Revlimid. Prescribing Information.  US Food and Drug Administration. Updated May 2019. Accessed June 15, 2023.

Author Bio

Christy Li, PhD, completed her bachelor’s degree in Biochemistry and Molecular Biology from Boston University in 2011, and she received her PhD in Biochemistry and Cell Biology from Weill Cornell Graduate School of Medical Sciences in 2022. She works as a biomedical scientist, researching treatments to improve public health. Christy is a firm believer in the value of scientific literacy and of having diverse perspectives in the scientific community as a means of health empowerment.