Eltrombopag monotherapy can improve hematopoiesis in patients with low to intermediate risk-1 myelodysplastic syndrome

Abstract

Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders characterized by cytopenia and a propensity to develop acute myeloid leukemia (AML). The management of lower-risk (LR) MDS with persistent cytopenias remains suboptimal. Eltrombopag (EPAG), a thrombopoietin receptor agonist, can improve platelet counts in LR-MDS and tri-lineage hematopoiesis in aplastic anemia (AA). We conducted a phase 2 dose modification study to investigate the safety and efficacy of EPAG in LR-MDS. EPAG dose was escalated from 50 mg/day, to a maximum of 150 mg/day over a period of 16 weeks. The primary efficacy endpoint was hematologic response at 16-20 weeks. Eleven of 25 (44%) patients responded; five and six patients had uni- or bi-lineage hematologic responses, respectively. The predictors of response were presence of a PNH clone, marrow hypocellularity, thrombocytopenia with or without other cytopenia, and elevated plasma thrombopoietin levels at study entry. The safety profile was consistent with previous EPAG studies in AA; no patients discontinued drug due to adverse events. Three patients developed reversible grade-3 liver toxicity and one patient had increased reticulin fibrosis. Ten patients discontinued EPAG after achieving a robust response (median time 16 months); four of them reinitiated EPAG due to declining counts, and all attained a second robust response. Six patients had disease progression not associated with expansion of mutated clones and no patient progressed to AML on study. In conclusion, EPAG was well-tolerated and effective in restoring hematopoiesis in patients with low to intermediate-1 risk MDS. This study was registered at clinicaltrials.gov as #NCT00932156.

Eltrombopag for myelodysplastic syndromes or chronic myelomonocytic leukaemia with no excess blasts and thrombocytopenia: a French multicentre retrospective real‐life study

“…The toxicity profile of ELT was comparable with that observed in previous studies. The main ELT-related adverse events were a relatively low incidence of thrombotic events; however, higher than observed in the Oliva et al 11 or Vicente et al 16 controlled clinical trials. However, most of our present patients who experienced thromboembolic events had a history of similar complications and those patients were probably excluded from the controlled clinical trials of Oliva et al 11 and Vicente et al 16 Our present results suggest caution with the indication of ELT in patients with a thromboembolic history.…”

“…d'Annecy Genevois, Pringy, 13 Service d'H ematologie, Centre Hospitalier Universitaire d'Amiens, Amiens, 14 Service d'H ematologie et Th erapie Cellulaire, Centre Hospitalier Universitaire de Poitiers, Poitiers, 15 Service d'H ematologie, Centre Hospitalier de Perpignan, Perpignan, 16 Service de M edecine Interne, Hôpital Saint-Antoine, AP-HP, Paris, France,…”

Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

“…Beyond IST therapy, thrombopoietin receptor agonists (TPO-RA), highly effective in AA either frontline in association with IST or as a single agent in relapsed/refractory patients, have been studied in MDS with variable response rates [ 136 , 137 , 138 , 139 , 140 , 141 ]. In a very recent phase I/II trial on low-risk MDS [ 142 ], eltrombopag was given at the maximal dose of 150 mg/day, inducing an ORR of 44%, significantly associated with marrow hypocellularity. Of note, no progression to AML was observed, and a phase III study on low-risk thrombocytopenic MDS cases is ongoing [ 138 ].…”

Challenges and Advances in Managing Thrombocytopenic Cancer Patients

“…The full study has not been published yet. Eltrombopag was also shown to increase white blood cell counts and hemoglobin levels in some patients in a small study of low-int risk MDS patients [ 78 ].…”