TY - JOUR AU - Alana Vicente, AU - Bhavisha A. Patel, AU - Fernanda Gutierrez-Rodrigues, AU - Emma Groarke, AU - Valentina Giudice, AU - Jennifer Lotter, AU - Xingmin Feng, AU - Sachiko Kajigaya, AU - Barbara Weinstein, AU - Evette Barranta, AU - Matthew J. Olnes, AU - Ankur R. Parikh, AU - Maher Albitar, AU - Colin O. Wu, AU - Ruba Shalhoub, AU - Katherine R. Calvo, AU - Danielle M. Townsley, AU - Phillip Scheinberg, AU - Cynthia E. Dunbar, AU - Neal S. Young, AU - Thomas Winkler, PY - 2020/12/01 Y2 - 2024/03/29 TI - Eltrombopag monotherapy can improve hematopoiesis in patients with low to intermediate risk-1 myelodysplastic syndrome JF - Haematologica JA - haematol VL - 105 IS - 12 SE - Articles DO - 10.3324/haematol.2020.249995 UR - https://haematologica.org/article/view/9761 SP - 2785-2794 AB - 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. ER -