Treatment of Lower Risk Myelodysplastic Syndromes

Valeria Santini

doi:10.3390/hemato3010013

Abstract

Purpose of review: Management and Optimization of therapy for lower-risk myelodysplastic syndromes will be reviewed here. Recent findings: Lower-risk MDS typically present with clinical manifestations of anemia, which is the most frequently encountered cytopenia in this setting. While therapy with erythropoietic stimulating agents (ESAs) is used in the vast majority of cases, if correctly selected, some patients do not respond, or become irresponsive to ESAs. Novel agents with very different modes of action show promising clinical results in anemic LR-MDS refractory/relapsed after ESAs. Luspatercept, a TGFbeta family ligand trap, induces nearly 50% of transfusion independence in LR MDS. Another investigational agent showing efficacy and possibly disease modifying activity is the telomerase inhibitor imetelstat. Modulation of dose and schedule of hypomethylating agents, both injectable and oral, is currently being explored, and preliminary results are positive. There is still no standard therapeutic approach for thrombocytopenic and neutropenic LR MDS, although they do represent a smaller proportion of cases. Immunosuppressive treatments, as well as TPO mimetics, could represent a good option in selected MDS cases. Summary: At present, the availability of novel active agents allows the planning of sequential therapy, especially for anemic LR MDS. Better diagnosis and prognostic stratification may allow a more precise and personalized treatment.

Highlights

There is still no standard therapeutic approach for thrombocytopenic and neutropenic LR myelodysplastic syndromes (MDS), they do represent a smaller proportion of cases
Summary: At present, the availability of novel active agents allows the planning of sequential therapy, especially for anemic LR MDS
We refer to international prognostic scoring system (IPSS-R) categories to prescribe treatments, we have to acknowledge that there is a further level of granularity in prognostic variables and that we should individualize even more our evaluation of risk

Summary

Introduction

Only 31.8% of treated patients had a response, vs 4.4% of placebo ones [8] This outcome is due to the design of the study, which provoked problems in the evaluation of its outcome, and difficulties in applying IWG criteria for frequent suspension of treatment when Hb level was approaching 12 g/dL, together with the inclusion of numerous transfusion dependent patients and the use of a weight adjusted dose of erythropoietin alpha instead of the standard fixed dose [8]. The widespread use of biosimilar erythropoietic agents seems to yield the same rate patients with MDS, as demonstrated by an early study in which deep vein thrombosis of response in treated patients [14]. Several novel agents are under evaluation in the setting of ESA relapsed/refractory

Possibletherapeutic therapeuticagents agentsininLR

Findings

Lenalidomide mediates the ubiquitination and degradation of with