Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia

Michael Dickinson, Honar Cherif, Pierre Fenaux, Moshe Mittelman, Amit Verma, Maria Socorro O Portella, Paul Burgess, Pedro Marques Ramos, Jeea Choi and Uwe Platzbecker

Key points

  • Eltrombopag/azacitidine was inferior to placebo/azacitidine in higher-risk MDS patients with respect to platelet-related and survival endpoints.

  • Findings from this study do not indicate a role for combining eltrombopag with azacitidine in patients with intermediate/high-risk MDS.


Azacitidine treatment for (MDS) generally exacerbates thrombocytopenia during the first treatment cycles. SUPPORT, a Phase III, randomized, double-blind, placebo-controlled study (NCT02158936), investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. IPSS intermediate-1, intermediate-2 or high-risk MDS patients with baseline platelets <75x109/L were randomized 1:1 to eltrombopag (starting 200 mg/day [East Asians: 100 mg/day], maximum 300 mg/day [East Asians: 150 mg/day]) or placebo, plus azacitidine (75 mg/m2 sc once daily for 7 days, every 28 days). Primary endpoint was the proportion of patients platelet transfusion-free during cycles 1-4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely as efficacy outcomes crossed the predefined futility threshold, and for safety reasons. At final termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary endpoint (OR 0.37; 95%CI 0.21, 0.65; two-sided P=0.001). Overall response (IWG criteria; complete, marrow or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment (OR 0.51; 95%CI 0.30, 0.86; nominal P=0.005). There was no difference in hematologic improvement in any cell lineage between the two arms. There was no improvement in overall survival (HR 1.42; 95%CI 0.97, 2.08; nominal P=0.164) or progression-free survival (HR 1.47; 95%CI 1.05, 2.07; nominal P=0.060). AEs with greater occurrence (≥10%) in the eltrombopag versus placebo arm were febrile neutropenia and diarrhea. Compared with azacitidine alone, eltrombopag plus azacitidine worsened platelet recovery, with lower response rates and a trend toward increased progression to AML.

  • Submitted June 19, 2018.
  • Accepted September 24, 2018.