# Lower-risk myelodysplastic syndromes

Source: https://onco.cc/cancers/mds-lower-risk/  
OnCo record `mds-lower-risk` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Lower-risk myelodysplastic syndromes rarely turn into leukaemia quickly; the problem is anaemia and the transfusions it demands. Erythropoietin, then luspatercept (COMMANDS) and the telomerase blocker imetelstat (IMerge), free many patients from transfusions for months or years, and lenalidomide does the same for the del(5q) subtype.

## Summary

Risk in myelodysplastic syndromes is scored by IPSS-R (blasts, cytogenetics and depth of cytopenias) and now IPSS-M, which adds mutations such as SF3B1 (favourable) and TP53 (adverse). Very low, low and intermediate IPSS-R groups, or IPSS-M low and moderate-low, are lower risk: median survival is measured in years and leukaemic transformation is uncommon, so treatment aims at the cytopenias and their consequences, chiefly transfusion-dependent anaemia with iron overload, and at quality of life. Watchful waiting is right for patients without symptoms.

Anaemia treatment is stepwise. Erythropoiesis-stimulating agents help around half of patients with a serum erythropoietin below 500 U/L. Lenalidomide gives transfusion independence to most patients with del(5q). Luspatercept, a TGF-beta superfamily ligand trap that releases late-stage red cell maturation, was approved in 2020 after MEDALIST for ring-sideroblast disease after erythropoietin failure, and COMMANDS (2023) moved it to first line: 58.5 percent of transfusion-dependent, erythropoietin-naive patients became transfusion independent for at least 12 weeks with a haemoglobin rise, against 31.2 percent on epoetin alfa. Imetelstat, the first telomerase inhibitor, was approved in 2024 after IMerge: in erythropoietin-refractory patients, 39.8 percent became transfusion independent for eight weeks and 28 percent for 24 weeks, against 15 and 3.3 percent on placebo, at the cost of neutropenia and thrombocytopenia.

Other cytopenias have fewer options: thrombopoietin agonists in trials, G-CSF for neutropenic infection, and iron chelation for transfusional iron overload (TELESTO). Allogeneic transplant is deferred until the disease progresses. Elritercept and other activin traps, oral hypomethylating agents at low dose, and drugs against the SF3B1 spliceosome defect are in trials, and IPSS-M is revealing that some patients labelled lower risk carry higher-risk mutations and should be treated accordingly.

## Fields

- Kind: Cancer
- Last checked: 2026-09-17
- Also known as: Low-risk MDS; IPSS-R very low, low and intermediate MDS; Lower-risk myelodysplastic neoplasms; Transfusion-dependent lower-risk MDS
- Tags: subtype-page
- Group: haematologic
- Burden: About two-thirds of people with myelodysplastic syndromes have lower-risk disease by IPSS-R; most are over 70, and anaemia rather than leukaemia is what shapes their lives, with many needing regular transfusions.
- Subtypes: MDS with low blasts, IPSS-R very low or low; MDS with SF3B1 mutation and ring sideroblasts (luspatercept); MDS with isolated del(5q) (lenalidomide); Transfusion-dependent lower-risk MDS after erythropoietin failure (imetelstat, luspatercept); Hypoplastic MDS (immunosuppression); IPSS-R intermediate MDS reclassified by IPSS-M
- Biomarkers: IPSS-R and IPSS-M scores; Serum erythropoietin level; Ring sideroblasts and SF3B1 mutation; del(5q); Transfusion burden; Serum ferritin and iron overload; TP53 and other adverse mutations on IPSS-M

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/mds-lower-risk/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/mds-lower-risk/#overview [3 state-of-the-art points]
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/mds-lower-risk/#what-it-is [6 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/mds-lower-risk/#finding-it [7 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/mds-lower-risk/#treating-it [4 settings, 3 decisions with options]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/mds-lower-risk/#evidence [8 trials, 2 key papers, 7 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/mds-lower-risk/#science [2 targets]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/mds-lower-risk/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/mds-lower-risk/#living-with-it [16 questions, 6 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/mds-lower-risk/coming/ [6 medicines, 7 trials, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/mds-lower-risk/data/ [36 connected records]

## Standard of care

- Asymptomatic, no transfusions: Observation with blood counts every three to six months; no treatment. ([Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/))
- Anaemia, first line: Luspatercept for ring-sideroblast or SF3B1-mutated disease and for transfusion-dependent patients (COMMANDS); erythropoiesis-stimulating agent where serum erythropoietin is below 500 U/L; lenalidomide for del(5q). ([Luspatercept](https://onco.cc/drugs/luspatercept/), [Epoetin alfa](https://onco.cc/drugs/epoetin-alfa/), [Darbepoetin alfa](https://onco.cc/drugs/darbepoetin-alfa/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/))
- Anaemia after erythropoietin or luspatercept failure: Imetelstat (IMerge); luspatercept if not yet used; low-dose hypomethylating agent; trials of elritercept and other agents. ([Imetelstat](https://onco.cc/drugs/imetelstat/), [Luspatercept](https://onco.cc/drugs/luspatercept/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular B](https://onco.cc/trials/nct06499285/), [Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)](https://onco.cc/trials/nct05308264/), [RVU120 for Treatment of Anemia in Patients With Lower-risk Myelodysplastic Neoplasms](https://onco.cc/trials/nct06243458/))
- Supportive care: Red cell transfusion to symptoms, iron chelation once ferritin is persistently high, G-CSF for recurrent neutropenic infection, platelet transfusion for bleeding. ([Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/), [Growth factors: G-CSF and febrile neutropenia prevention](https://onco.cc/technologies/g-csf-growth-factors/))

## State of the art

- Luspatercept is first-line treatment for transfusion-dependent anaemia after COMMANDS, and imetelstat gives a second line that works after erythropoietin fails.
- IPSS-M has shifted treatment for many patients by finding high-risk mutations in disease that looked lower risk.
- Transfusion independence, not survival, is the endpoint that has driven every approval.

## Open problems

- No approved treatment for thrombocytopenia or neutropenia in lower-risk disease.
- Whether early disease-modifying treatment changes the natural history rather than the transfusion count.
- Iron overload management and quality of life are under-studied.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Myelodysplastic_syndrome
- Wikipedia: https://en.wikipedia.org/wiki/Myelodysplastic_syndrome
- NCCN Guidelines: Myelodysplastic Syndromes: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1446

## Connected records

- cancers: [Higher-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-higher-risk/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/)
- technologies: [Growth factors: G-CSF and febrile neutropenia prevention](https://onco.cc/technologies/g-csf-growth-factors/), [Transfusion support and anaemia management](https://onco.cc/technologies/transfusion-support/)
- terms: [Ageing tissue and clonal fields: cancer as a disease of old tissue](https://onco.cc/terms/ageing-tissue-field-theory/), [Anaemia](https://onco.cc/terms/anaemia/), [del(5q) (5q- syndrome and lenalidomide response)](https://onco.cc/terms/del5q/), [Disease-specific staging and risk systems (FIGO, Ann Arbor, IPI, R-ISS, ELN, IMDC)](https://onco.cc/terms/staging-systems/), [IPSS-R and IPSS-M (myelodysplastic syndrome risk scores)](https://onco.cc/terms/ipss-m-ipss-r/), [SF3B1 mutation](https://onco.cc/terms/sf3b1-mutation/)
- trials: [A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular B](https://onco.cc/trials/nct06499285/), [COMMANDS](https://onco.cc/trials/commands/), [IMerge](https://onco.cc/trials/imerge/), [MEDALIST](https://onco.cc/trials/medalist/), [RVU120 for Treatment of Anemia in Patients With Lower-risk Myelodysplastic Neoplasms](https://onco.cc/trials/nct06243458/), [Study of DISC-0974 (RALLY-MF) in Participants With Myelofibrosis or Myelodysplastic Syndrome and Anemia](https://onco.cc/trials/nct05320198/), [Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)](https://onco.cc/trials/nct05308264/), [TELESTO](https://onco.cc/trials/telesto/)
- key papers: [COMMANDS: luspatercept versus epoetin alfa as first treatment for anaemia in lower-risk MDS needing transfusions](https://onco.cc/key-papers/paper-commands-luspatercept-mds-lancet-2023/), [IMerge: imetelstat, a telomerase inhibitor, for transfusion-dependent lower-risk MDS after erythropoietin has failed](https://onco.cc/key-papers/paper-imerge-imetelstat-mds-lancet-2024/)
- drugs: [Azacitidine](https://onco.cc/drugs/azacitidine/), [Darbepoetin alfa](https://onco.cc/drugs/darbepoetin-alfa/), [Epoetin alfa](https://onco.cc/drugs/epoetin-alfa/), [Imetelstat](https://onco.cc/drugs/imetelstat/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Luspatercept](https://onco.cc/drugs/luspatercept/)

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JSON: https://onco.cc/api/v1/entities/mds-lower-risk.json