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Teaching pack: Myelodysplastic syndromes / neoplasms (MDS)

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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

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  1. Teaching pack · Cancer · haematologic

    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.

    Teaching pack: Myelodysplastic syndromes / neoplasms (MDS) · OnCo, CC BY 4.0 · not medical advice1 / 9
  2. What it is

    In two paragraphs

    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.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Lower risk, anaemiaESA 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 (imetelstat)
    Higher risk, transplant candidateAllogeneic HSCT, usually after hypomethylating-agent cytoreduction; BMT CTN 1102 showed a survival benefit for transplant in 50-75-year-olds.not mapped
    Higher risk, not transplant candidateAzacitidine (AZA-001) or decitabine / oral decitabine-cedazuridine until progression; supportive care and trials.NCCN Category 1 (azacitidine)
    Supportive care, all risksTransfusion, iron chelation for transfusional iron overload (TELESTO), infection management, G-CSF for neutropenic infection.not mapped
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  4. State of the art

    Where the field stands

    • 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.
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  5. History

    How we got here

    1. 1982FAB classification of MDS
    2. 1997IPSS risk score
    3. 2004Azacitidine approved
    4. 2005Lenalidomide for del(5q)
    5. 2012IPSS-R
    6. 2020Luspatercept approved
    7. 2022IPSS-M and WHO5/ICC
    8. 2023Higher-risk combinations fail
    9. 2024Imetelstat approved
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  6. Pipeline

    What is coming

    • Imetelstat (product)
    • Luspatercept (product)
    • Allogeneic stem cell transplantation (technology)
    • Magrolimab (product)
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  7. Open problems

    What nobody has solved

    • 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.
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  8. Quiz

    Check understanding

    1. Why does venetoclax work in leukaemia?
      Answer
      It blocks BCL-2, the protein that stops leukaemia cells from self-destructing, so the built-in death programme (apoptosis) can run; used in CLL (fixed duration with obinutuzumab) and AML (with azacitidine).
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  9. Sources

    Read the primary sources

    • IPSS-M (NEJM Evidence 2022): https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200008
    • NCI PDQ: MDS: https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq
    • SEER: MDS: https://seer.cancer.gov/statfacts/html/mds.html
    • Wikipedia: https://en.wikipedia.org/wiki/Myelodysplastic_syndrome
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1446
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