The combination of eltrombopag and azacitidine in patients with comorbid myelodysplastic syndrome (MDS) and thrombocytopenia may lead to worse overall survival than treatment with single-agent azacitidine, according to a study published in Blood.

Of patients with MDS, 40% to 65% experience thrombocytopenia, which predicts worse prognosis and is exacerbated by the hypomethylating agents (such as azacitidine) used to treat MDS. Thrombocytopenia can be treated with eltrombopag, an oral, non-peptide, thrombopoietin receptor agonist, and recent clinical trials with single-agent eltrombopag have reported that it is tolerated well by patients with low- and high-risk MDS.

In a randomized, double-blind, placebo-controlled, international, multicenter, phase 3 study, researchers randomly assigned 356 patients with intermediate- or high-risk MDS to 2 study arms: eltrombopag plus azacitidine (179 patients) or placebo plus azacitidine (177 patients). The patients received 75 mg/m2 of azacitidine once per day for 7 days, every 28 days. All patients except East Asians received eltrombopag or placebo with a starting dose of 200 mg/day, adjusted in 100 mg increments to a maximum of 300 mg/day based on the patients’ platelet counts. For East Asian patients, the starting dose of eltrombopag or placebo was 100 mg/day, adjusted in 50 mg increments to a maximum of 150 mg/day based on their platelet counts. All patients received eltrombopag or placebo from day 1 of treatment.

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The primary outcome was the proportion of platelet transfusion-independent patients after 4 cycles of azacitidine therapy. Secondary outcomes were overall survival (OS), progression-free survival (PFS), disease response and duration of response, progression to AML, safety, and tolerability. However, the study was terminated early by recommendation of an independent data monitoring committee because efficacy outcomes had crossed the predefined futility threshold.

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At termination, 16% of patients receiving eltrombopag and 31% of patients receiving placebo were platelet transfusion-independent. Patients receiving eltrombopag were at a higher risk of experiencing disease progression or death (hazard ratio = 1.38 according to central review). Overall response was found in 20% of patients receiving eltrombopag and 35% of patients receiving placebo.

Though there was no significant difference in the number of overall deaths between the two study arms (14% of patients receiving eltrombopag vs 12% of patients receiving placebo), the data suggested that patients receiving eltrombopag were at a higher risk of disease progression and progression to AML.

“The efficacy and safety results of this study contrast with those of recent clinical studies of eltrombopag monotherapy in patients with MDS,” the authors concluded. “Findings from this study do not indicate a role for combining eltrombopag with azacitidine in patients with intermediate/high-risk MDS.”

Disclosures: Multiple authors declare affiliations with industry. Please refer to the original study for a full list of disclosures.


1. Dickinson M, Cherif H, Fenauz P, et al. Azacitidine with or without eltrombopag for first-line treatment or intermediate- or high-risk MDS with thrombocytopenia [published online October 10, 2018]. doi: 10.1182/blood-2018-06-855221