Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (ASPIRE): a randomised, placebo-controlled, phase 2 trial

Mittelman, Moshe; Platzbecker, Uwe; Afanasyev, Boris; Grosicki, Sebastian; Wong, Raymond; Anagnostopoulos, Achilles; Brenner, Benjamin; Denzlinger, Claudio; Rossi, Giuseppe; Nagler, Arnon; García-Delgado, R.; Portella, Maria Socorro O; Zhu, Zewen; Selleslag, Dominik

doi:10.1016/s2352-3026(17)30228-4

Cited by 84 publications

(79 citation statements)

References 17 publications

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“…The efficacy and safety results of this study contrast with those of recent clinical studies of eltrombopag monotherapy in patients with MDS, which showed an acceptable safety profile of eltrombopag in patients with low-and high-risk MDS and positive outcomes on thrombocytopenia. [15][16][17]32 There were no indicators that would predict the outcome of this phase 3 trial. 18,19 Preclinical and single-agent clinical studies of eltrombopag suggest that as a single agent, eltrombopag suppresses malignant myeloid blast proliferation [33][34][35][36] ; hence, the findings of this trial were unexpected.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14] More recent clinical trials with single-agent eltrombopag at doses of #300 mg/day have also demonstrated improvements in platelet counts and reductions in the incidence of thrombocytopenic events in low-risk MDS, high-risk MDS, and AML. [15][16][17] Results of phase 1 and 2 trials have suggested that the combination of eltrombopag with azacitidine is feasible and well tolerated. 18,19 Additionally, a phase 1/2 study in lower risk MDS patients showed that the combination of another TPO-RA, romiplostim, with azacitidine was well tolerated, although blast cell counts were transiently increased in some patients.…”

Section: Introductionmentioning

confidence: 99%

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

Dickinson

Cherif

Fenaux

et al. 2018

Blood

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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 × 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Dickinson

Cherif

Fenaux

et al. 2018

Blood

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“…7,8 Eltrombopag did not achieve the prespecified 30% reduction in clinically relevant thrombocytopenic events (primary endpoint) compared with placebo in high-risk patients with MDS recruited into the advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (ASPIRE) clinical trial. 9 Nevertheless, patients in the eltrombopag arm had fewer clinically relevant thrombocytopenic events than those in the placebo arm. Eltrombopag has multilineage activity in aplastic anemia, 10 and this merits further study in MDS.…”

Section: Thrombocytopenia As a Prognostic Factor In Myelodysplasticmentioning

confidence: 99%

Thrombocytopenia and platelet transfusion in myelodysplastic syndromes

Bowen¹,

Καρακάντζα

2020

Transfusion

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In this issue of TRANSFUSION, Kathleen Cheok and colleagues report a study of clinical and hematological data from thrombocytopenic patients in the South Australian myelodysplastic syndrome (MDS) Registry. They correlate these data with platelet transfusion data from the South Australian Red Cross Blood Service (including the HLA Registry) together with HLA alloantibody data from the South Australian Tissue Typing and Immunologic Services. The authors propose that providers consider routinely screening female patients for HLA antibodies at the start of any disease modifying therapy.

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“…Despite increased platelet counts and decreased numbers of bleeding events and platelet transfusions, treatment with romiplostim did not have an effect on overall survival. Eltrombopag also reduced clinically relevant thrombocytopenic events in MDS . However, a multicentre trial had to be terminated due to a possible negative interaction between this drug and the hypomethylating agent (HMA) Aza .…”

Section: Treatment Of Lower‐risk Mdsmentioning

confidence: 99%