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

Abstract

Azacitidine treatment of myelodysplastic syndromes (MDSs) generally exacerbates thrombocytopenia during the first treatment cycles. A Study of Eltrombopag in Myelodysplastic Syndromes Receiving Azacitidine (SUPPORT), a phase 3, randomized, double-blind, placebo-controlled study, investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. International Prognostic Scoring System intermediate-1, intermediate-2, or high-risk MDS patients with baseline platelets <75 × 109/L were randomized 1:1 to eltrombopag (start, 200 mg/d [East Asians, 100 mg/d], maximum, 300 mg/d [East Asians, 150 mg/d]) or placebo, plus azacitidine (75 mg/m2 subcutaneously once daily for 7 days every 28 days). The primary end point was the proportion of patients platelet transfusion-free during cycles 1 through 4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely because efficacy outcomes crossed the predefined futility threshold and for safety reasons. At termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary end point. Overall response (International Working Group criteria; complete, marrow, or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment. There was no difference in hematologic improvement in any cell lineage between the 2 arms. There was no improvement in overall or progression-free survival. Adverse events with ≥10% occurrence in the eltrombopag vs 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 acute myeloid leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02158936.

• Authors: Michael Dickinson, Honar Cherif, Pierre Fenaux, Moshe Mittelman, Amit Verma, Maria Socorro O Portella, Paul Burgess, Pedro Marques Ramos, Jeea Choi, Uwe Platzbecker, SUPPORT study investigators
• Journal: Blood (Blood) Vol. 132 Issue 25 Pg. 2629-2638 (12 20 2018) ISSN: 1528-0020 [Electronic] United States
• PMID: 30305280 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by The American Society of Hematology.

Chemical References

• Benzoates
• Hydrazines
• Pyrazoles
• Azacitidine
• eltrombopag

Topics

• Adult
• Aged
• Aged, 80 and over
• Azacitidine (administration & dosage, adverse effects)
• Benzoates (administration & dosage, adverse effects)
• Double-Blind Method
• Female
• Humans
• Hydrazines (administration & dosage, adverse effects)
• Male
• Middle Aged
• Myelodysplastic Syndromes (complications, mortality, therapy)
• Platelet Transfusion
• Pyrazoles (administration & dosage, adverse effects)
• Risk Factors
• Thrombocytopenia (complications, mortality, therapy)