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 K. Verma, Maria Socorro O. Portella, Paul Burgess, Pedro Marques Ramos, Jeea Choi, Uwe Platzbecker

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 3 109/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.

Original languageEnglish (US)
Pages (from-to)2629-2638
Number of pages10
JournalBlood
Volume132
Issue number25
DOIs
StatePublished - Dec 20 2018

Fingerprint

Azacitidine
Myelodysplastic Syndromes
Thrombocytopenia
Platelets
Placebos
Blood Platelets
Therapeutics
Clinical Trials Data Monitoring Committees
Medical Futility
Febrile Neutropenia
Platelet Transfusion
Cell Lineage
eltrombopag
Acute Myeloid Leukemia
Disease-Free Survival
Diarrhea
Bone Marrow
Research Personnel
Safety
Recovery

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Dickinson, M., Cherif, H., Fenaux, P., Mittelman, M., Verma, A. K., Portella, M. S. O., ... Platzbecker, U. (2018). Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. Blood, 132(25), 2629-2638. https://doi.org/10.1182/blood-2018-06-855221

Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. / Dickinson, Michael; Cherif, Honar; Fenaux, Pierre; Mittelman, Moshe; Verma, Amit K.; Portella, Maria Socorro O.; Burgess, Paul; Ramos, Pedro Marques; Choi, Jeea; Platzbecker, Uwe.

In: Blood, Vol. 132, No. 25, 20.12.2018, p. 2629-2638.

Research output: Contribution to journalArticle

Dickinson, M, Cherif, H, Fenaux, P, Mittelman, M, Verma, AK, Portella, MSO, Burgess, P, Ramos, PM, Choi, J & Platzbecker, U 2018, 'Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia', Blood, vol. 132, no. 25, pp. 2629-2638. https://doi.org/10.1182/blood-2018-06-855221
Dickinson, Michael ; Cherif, Honar ; Fenaux, Pierre ; Mittelman, Moshe ; Verma, Amit K. ; Portella, Maria Socorro O. ; Burgess, Paul ; Ramos, Pedro Marques ; Choi, Jeea ; Platzbecker, Uwe. / Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. In: Blood. 2018 ; Vol. 132, No. 25. pp. 2629-2638.
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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 3 109/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.",
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AU - Verma, Amit K.

AU - Portella, Maria Socorro O.

AU - Burgess, Paul

AU - Ramos, Pedro Marques

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