Lower-Risk MDS with Symptomatic Anaemia After Erythropoiesis-Stimulating Agent Failure
Clinical scenario
This protocol covers lower-risk myelodysplastic syndrome (IPSS-R up to 3.5) presenting with symptomatic anaemia — haemoglobin generally below 10 g/dl — and no del(5q) cytogenetic abnormality. For therapeutic purposes, this lower-risk category includes very low-, low-, and part of intermediate-risk IPSS-R patients.
Why first-line treatment was not sufficient
First-line therapy with erythropoiesis-stimulating agents (ESA) — erythropoietin or darbepoetin, with or without granulocyte colony-stimulating factor — did not achieve the expected erythroid response according to IWG 2006 criteria within 8–12 weeks. This failure to reach a meaningful erythroid response or transfusion independence is the clinical trigger for the second-line protocol described here.
Second-line approach (partial overview)
Following ESA failure, the protocol defines specific second-line interventions selected according to disease subtype and patient characteristics — including an agent that promotes erythroid maturation and immunosuppressive approaches for eligible patients. The complete eligibility criteria, sequencing, and full set of options are detailed in the structured protocol.
The treatment goal of this second-line strategy is red blood cell transfusion independence and a meaningful erythroid response.
References
For therapeutic purposes, the term 'lower-risk' MDS generally applies to cases with IPSS-R up to 3.5 including very low- and low-risk and part of intermediate-risk IPSS-R patients.
Symptomatic anaemia (generally if Hb <10 g/dl).
No del(5q).
After ESA failure in RBC transfusion-dependent MDS-RS, luspatercept is recommended [I, A].
After ESA failure, ATG (± cyclosporine) has efficacy in specific younger patient cohorts of lower-risk MDS [II, B].
Other second-line treatments for anaemia after ESA failure include LEN ± ESA [II, B] and HMAs [II, B], but they are not approved in Europe for this indication.
ATG ± cyclosporine, can yield an erythroid response (associated with response of other cytopaenias, especially thrombocytopaenia) in 25%–40% of patients [II, B].
DOI: 10.1016/j.annonc.2020.11.002
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