cancersCancer

Myelodysplastic syndromes / neoplasms (MDS)

Bone-marrow disorders where blood cells are made badly and too few reach the blood; a third progress to acute leukaemia. Treatment ranges from transfusions and growth factors to hypomethylating drugs and, for the fit, transplant.

MDS are clonal myeloid neoplasms with ineffective haematopoiesis, cytopenias, dysplasia and variable risk of transformation to AML. Risk is stratified by IPSS-R and, since 2022, the molecular IPSS-M, which incorporates mutations (TP53 multi-hit, ASXL1, RUNX1, SF3B1 among 31 genes). The WHO 2022 and ICC classifications define genetically specified entities (SF3B1-mutant, del(5q), biallelic TP53) and renamed the group 'myelodysplastic neoplasms'.

Lower-risk disease is treated for anaemia: erythropoiesis-stimulating agents, lenalidomide for del(5q), luspatercept (MEDALIST 2020, COMMANDS 2023 first line), and imetelstat (IMerge, 2024) after ESA failure. Higher-risk disease is treated with hypomethylating agents (azacitidine, decitabine, oral decitabine-cedazuridine) and, for the fit with a donor, allogeneic transplant, the only cure. Three large phase 3 additions to azacitidine failed in 2023-24 (magrolimab ENHANCE, sabatolimab STIMULUS-MDS2, venetoclax VERONA), leaving azacitidine alone as the higher-risk standard.

Open problems: TP53-mutant MDS, post-HMA failure (median survival under six months), and how to use IPSS-M to time transplant.

State of the art today

IPSS-M (2022) reclassifies about half of patients relative to IPSS-R and is now the recommended risk model.
Two new drugs for lower-risk anaemia in four years: luspatercept and imetelstat, both reducing transfusion dependence.
Higher-risk MDS has had no new drug since azacitidine: the 2023-24 failures of magrolimab, sabatolimab and venetoclax combinations were a field-wide setback.
Allogeneic transplant remains the only cure; reduced-intensity conditioning extends it to older patients.

Who it affects

MDS affects around 4-5 per 100,000 people per year overall, rising steeply with age (median age ~70), according to SEER.

Group

haematologic

Where the cases are

Cases by country · GLOBOCAN 2022

All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Lower risk, anaemia

ESA if serum EPO <500; luspatercept first line (COMMANDS) or after ESA failure (MEDALIST); imetelstat after ESA failure (IMerge); lenalidomide for del(5q).

NCCN · Category 1 (luspatercept), Category 2A (ime…

LuspaterceptImetelstatLenalidomide

Higher risk, transplant candidate

Allogeneic HSCT, usually after hypomethylating-agent cytoreduction; BMT CTN 1102 showed a survival benefit for transplant in 50-75-year-olds.

NCCN Guidelines: MDS

Allogeneic stem cell transplantationAzacitidine

Higher risk, not transplant candidate

Azacitidine (AZA-001) or decitabine / oral decitabine-cedazuridine until progression; supportive care and trials.

NCCN · Category 1 (azacitidine)

AzacitidineDecitabine + cedazuridine (oral)

Supportive care, all risks

Transfusion, iron chelation for transfusional iron overload (TELESTO), infection management, G-CSF for neutropenic infection.

Transfusion support and anaemia management Growth factors: G-CSF and febrile neutropenia prevention

Subtypes & biomarkers

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Subtypes

MDS with low blasts (MDS-LB)
MDS with SF3B1 mutation (ring sideroblasts)
MDS with del (5q)
MDS with biallelic TP53 inactivation
MDS with increased blasts (IB1, IB2)
Hypoplastic MDS
Therapy-related MDS

Biomarkers clinicians test

IPSS-R and IPSS-M risk
Cytogenetics (del(5q), -7, complex karyotype)
NGS panel (SF3B1, TP53, ASXL1, RUNX1, TET2, DNMT3A, SRSF2, U2AF1)
Blast percentage
Serum EPO level (ESA response prediction)
Transfusion burden

Target prevalence in this cancer

History

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1982FAB classification of MDS
Bennett and colleagues define refractory anaemia, RARS, RAEB, RAEB-T and CMML.
1997IPSS risk score
Greenberg's International Prognostic Scoring System combines blasts, cytogenetics and cytopenias.
2004Azacitidine approved
First drug approved for MDS (US); AZA-001 (2009) shows survival benefit in higher-risk disease.
Azacitidine
2005Lenalidomide for del(5q)
Transfusion independence in two-thirds of del(5q) patients (List et al.).
Lenalidomide
2012IPSS-R
Revised score with five cytogenetic groups and refined thresholds.
2020Luspatercept approved
MEDALIST in ring-sideroblast MDS after ESA failure; COMMANDS (2023) moves it to first line.
Luspatercept
2022IPSS-M and WHO5/ICC
Molecular risk model with 31 genes; classification renamed myelodysplastic neoplasms with genetically defined entities.
2023Higher-risk combinations fail
Magrolimab (ENHANCE) and sabatolimab (STIMULUS-MDS2) add nothing to azacitidine; VERONA (venetoclax) negative in 2024.
MagrolimabVenetoclaxAzacitidine
2024Imetelstat approved
IMerge: telomerase inhibitor achieves durable transfusion independence after ESA failure.
Imetelstat

Pipeline

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Not mapped hereTelomerase inhibitor (oligonucleotide)

Imetelstat · Rytelo

Not mapped hereErythroid maturation agent (activin receptor IIB ligand trap, Fc fusion)

Luspatercept · Reblozyl

WithdrawnMonoclonal antibody (anti-CD47)

Magrolimab

Allogeneic stem cell transplantation

Open problems

No drug has beaten azacitidine in higher-risk MDS.
TP53-mutant and complex-karyotype disease: median survival about a year even after transplant.
Clonal cytopenia of undetermined significance (CCUS): who to watch, who to treat.
Post-HMA failure has no standard.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov

Myelodysplastic syndromes / neoplasms (MDS)

condition: Myelodysplastic syndromes / neoplasms

Open on ClinicalTrials.gov →

within

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Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

USC Norris Comprehensive Cancer CenterLos Angeles, CA, USNCI comprehensive
via this cancer, Azacitidine
Walter and Eliza Hall Institute of Medical ResearchMelbourne, AU
via Growth factors: G-CSF and febrile neutropenia prevention, Venetoclax
Fred & Pamela Buffett Cancer CenterOmaha, NE, USNCI clinical
via Allogeneic stem cell transplantation
HOVONRotterdam, NL
via Venetoclax
Indiana University Melvin and Bren Simon Comprehensive Cancer CenterIndianapolis, IN, USNCI comprehensive
via Allogeneic stem cell transplantation
Juravinski Cancer Centre / Escarpment Cancer Research InstituteHamilton, ON, CA
via Allogeneic stem cell transplantation
Masonic Cancer Center, University of MinnesotaMinneapolis, MN, USNCI comprehensive
via Allogeneic stem cell transplantation
Montefiore Einstein Comprehensive Cancer CenterBronx, NY, USNCI comprehensive
via this cancer
Sylvester Comprehensive Cancer Center, University of MiamiMiami, FL, USNCI clinical
via this cancer
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterBaltimore, MD, USNCI comprehensive
via Allogeneic stem cell transplantation

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Myelodysplastic syndromes / neoplasms

Generated from this cancer's standard of care, biomarkers, and pipeline · 16 questions

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?
Why: Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example IPSS-R and IPSS-M risk, Cytogenetics, -7, complex karyotype), NGS panel, Blast percentage, Serum EPO level), and what were the results?
Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?
Why: Recognised subtypes for this cancer include MDS with low blasts, MDS with SF3B1 mutation, MDS with del.
Is germline (inherited) genetic testing recommended for me or my family?
Why: Inherited variants can change treatment and matter for relatives.

Lower risk, anaemia

For my situation (lower risk, anaemia), which of the standard options do you recommend and why?
Why: Guideline options include: ESA if serum EPO <500; luspatercept first line (COMMANDS) or after ESA failure (MEDALIST); imetelstat after ESA failure (IMerge); lenalidomide for del(5q).
Am I a candidate for Luspatercept, Imetelstat, Lenalidomide, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Higher risk, transplant candidate

For my situation (higher risk, transplant candidate), which of the standard options do you recommend and why?
Why: Guideline options include: Allogeneic HSCT, usually after hypomethylating-agent cytoreduction; BMT CTN 1102 showed a survival benefit for transplant in 50-75-year-olds.
Am I a candidate for Azacitidine, and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Higher risk, not transplant candidate

For my situation (higher risk, not transplant candidate), which of the standard options do you recommend and why?
Why: Guideline options include: Azacitidine (AZA-001) or decitabine / oral decitabine-cedazuridine until progression; supportive care and trials.
Am I a candidate for Azacitidine, Decitabine + cedazuridine (oral), and what side effects should I expect?
Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Supportive care, all risks

For my situation (supportive care, all risks), which of the standard options do you recommend and why?
Why: Guideline options include: Transfusion, iron chelation for transfusional iron overload (TELESTO), infection management, G-CSF for neutropenic infection.

Any stage

Are there clinical trials I could join, for example of Imetelstat, Luspatercept, Allogeneic stem cell transplantation, Magrolimab?
Why: Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?
Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
Why: Supportive care improves quality of life and helps patients complete treatment.
I read that “No drug has beaten azacitidine in higher-risk MDS”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.
I read that “TP53-mutant and complex-karyotype disease: median survival about a year even after transplant”. How does that affect my plan?
Why: Open problems are where trials and second opinions matter most.

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Everything relevant

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Direct links plus the targets, companies, and technologies of this cancer's products.

Key papers

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rctThe Lancet 2024changed practice

IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed

IMerge validated telomerase as a drug target in cancer, decades after its discovery, and gave a second-line option for MDS patients whose anaemia no longer responds to erythropoietin or luspatercept. The hint of clonal reduction is what makes the drug interesting beyond transfusion counts. Cytopenias require close monitoring in the first cycles.

rctThe Lancet 2023changed practice

COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions

COMMANDS moved luspatercept from second line (after ESA failure, MEDALIST trial) to first line, offering transfusion-dependent lower-risk MDS patients a better chance of transfusion freedom from the start. It changed guidelines and labels in 2023. Erythropoietin remains a reasonable and cheaper option for patients without ring sideroblasts or with low transfusion burden.