Eltrombopag treatment may require at least 24 weeks to show effectiveness against refractory severe aplastic anemia (rSAA), according to research presented in the journal Blood.

A phase 2 study (ClinicalTrials.gov Identifier: NCT01891994) in 40 patients with rSAA was undertaken to identify responses after 24 weeks of eltrombopag at a dosage of 150 mg daily, with lower dosages given to patients younger than 12 years. Responses were evaluated at 3 and 6 months.

The study results were analyzed in conjunction with those from a pilot study (ClinicalTrials.gov Identifier: NCT00922883). In the pilot study, responses in 43 patients with rSAA were evaluated at 12 to 16 weeks after initiation of eltrombopag treatment and with dose escalation from 50 mg to 150 mg daily.

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Both studies were nonrandomized, and results were combined for some analyses. Responses were defined by thresholds of improvement in 1 or more affected blood cell lineages including platelet count, erythroid response, and neutrophil count. Karyotyping and genetic sequencing were also performed throughout.

In the longer-term study, 50% of patients showed responses at 24 weeks. Five of these 20 patients had not yet shown responses by 12 weeks. Responses were 65% unilineage at 12 weeks. At 24 weeks, responses were 45% bilineage and 35% trilineage.

Five patients experienced relapse after discontinuation of eltrombopag due to strong response, but relapse was reversed in each patient upon restarting eltrombopag. Most patients who discontinued treatment had not experienced relapse by the time of the report.

Between both studies, 16 patients showed abnormal cytogenetic changes that mostly occurred rapidly on eltrombopag. Chromosome 7 changes occurred in 7 patients, 6 of whom did not respond to eltrombopag. Gene sequencing, however, did not reveal changes in suspected myeloid cancer-related genes associated with eltrombopag treatment.

One patient with cytogenetic changes developed myelodysplastic syndrome. Another patient was diagnosed with acute myeloid leukemia 10 weeks into eltrombopag treatment and died from sepsis while receiving chemotherapy.

The authors suggested further studies are needed to clarify the effects of eltrombopag on clonal evolution and recommended that treatment with eltrombopag be maintained for at least 6 months in order to determine its efficacy in patients with rSAA.


  1. Winkler T, Fan X, Cooper J, et al. Eltrombopag for refractory severe aplastic anemia: dosing, duration, long term outcomes and clonal evolution [published online April 16, 2019]. Blood. doi:10.1182/blood.2019000478