Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial

Olíva, Esther Natalie; Alati, Caterina; Santini, Valeria; Poloni, Antonella; Molteni, Alfredo; Niscola, Pasquale; Salvi, Flavia; Sanpaolo, Grazia; Balleari, Enrico; Germing, Ulrich; Fenaux, Pierre; Stamatoullas, Aspasia; Palumbo, Giuseppe A.; Salutari, Prassede; Impera, Stefana; Avanzini, Paolo; Cortelezzi, Agostino; Liberati, Anna Marina; Carluccio, Paola; Buccisano, Francesco; Voso, Maria Teresa; Mancini, Stefano; Kulasekararaj, Austin; Morabito, Fortunato; Bocchia, Monica; Cufari, Patrizia; Spiriti, Maria Antonietta Aloe; Santacaterina, Irene; D’Errigo, Maria Grazia; Bova, Irene; Zini, Gina; Latagliata, Roberto

doi:10.1016/s2352-3026(17)30012-1

Cited by 144 publications

(134 citation statements)

References 28 publications

(47 reference statements)

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“…In a subsequent randomised phase II study versus placebo in LR‐MDS with thrombocytopenia, romiplostim reduced the incidence of severe bleeding and platelet transfusions, but there was a suspected increase in the AML risk that was not confirmed with longer term follow‐up (Kantarjian et al , ). Eltrombopag also produces a platelet response in about 50% of patients, with no apparent increase in the risk of disease progression (Oliva et al , ), including with longer follow‐up (Oliva et al , ). However, long term follow‐up may be lacking in some studies, and the number of reported patients treated with eltrombopag, in particular, remains limited.…”

Section: How We Treat Lower‐risk(lr) Mdsmentioning

confidence: 99%

How we manage adults with myelodysplastic syndrome

2019

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Summary The prognosis in Myelodysplastic syndromes (MDS), although recently refined by molecular studies, remains largely based on conventional prognostic scores [International Prognostic Scoring System (IPSS), revised IPSS], classifying patients into “lower risk” MDS (LR‐MDS) and “higher risk” MDS (HR‐MDS). In LR‐MDS, treatment mainly aims at improving cytopenias, principally anaemia, while in HR‐MDS it aims at delaying disease progression and prolonging survival. In LR‐MDS without deletion 5q, anaemia is generally treated first by erythropoietic stimulating factors, while second line treatments are currently not approved [lenalidomide, hypomethylating agents (HMA), luspatercept] or rarely indicated (antithymocyte globulin). Lenalidomide has major efficacy in LR‐MDS with deletion 5q. Allogeneic stem cell transplantation (allo‐SCT) is sometimes considered in LR‐MDS, and iron chelation can be considered when multiple red blood cell transfusions are required. Allo‐SCT is the only potentially curative treatment for HR‐MDS; however, it is rarely applicable. It is generally preceded by intensive chemotherapy (IC) or HMA in patients with excess of marrow blasts (especially if >10%). In other patients, HMA can improve survival. The role of new drugs, including venetoclax or, in case of specific mutations, IDH1 or IDH2 inhibitors, is investigated. IC is mainly indicated as a bridge to allo‐SCT, in the absence of unfavourable karyotype.

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Section: How We Treat Lower‐risk(lr) Mdsmentioning

confidence: 99%

How we manage adults with myelodysplastic syndrome

2019

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“…A number of studies are evaluating eltrombopag in MDS, another TPO agonist. Results from the phase 1 single‐arm, randomized portion of the phase 2 superiority EQoL‐MDS study evaluating the efficacy and safety of eltrombopag in patients with lower‐risk MDS where recently published and reported significantly higher platelet responses (47% versus 3%, P = .0017) and fewer bleeding events (14% versus 42%, P = .0025) in the eltrombopag arm compared to placebo. No differences in leukemic transformation where observed (12% versus 16%, P = .81).…”

Section: Risk Adapted Therapymentioning

confidence: 99%

Myelodysplastic syndromes: 2018 update on diagnosis, risk‐stratification and management

2017

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“…largely reversible [55]. In contrast, clinical studies in patients with either low-risk or high-risk MDS did not show an increased risk of disease progression in those receiving eltrombopag monotherapy as compared with those receiving placebo [56][57][58]. However, an apparent increase in AML progression rate was noted in patients with high-risk MDS who were treated with eltrombopag in combination with azacytidine versus patients who received azacytidine alone (18% versus 11%, respectively) [59].…”

Section: Megakaryocyte Maturation and Proplatelet Formationmentioning

confidence: 99%

Thrombopoietin receptor agonists in hereditary thrombocytopenias

Rodeghiero

Pecci

Balduini

2018

Journal of Thrombosis and Haemostasis

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Hereditary thrombocytopenias (HTPs) constitute a heterogeneous group of diseases characterized by a reduction in platelet count and a potential bleeding risk. As a result of advances in diagnostic methods, HTPs are increasingly being identified, and appear to be less rare than previously thought. Most HTPs do not have effective treatments, except for platelet transfusion when bleeding occurs and in preparation for procedures associated with a risk of bleeding. Preliminary clinical evidence suggests that thrombopoietin receptor agonists (TPO-RAs) with an established use in the treatment of certain acquired thrombocytopenias are well tolerated and provide clinical benefits in patients with some forms of HTP. These drugs may therefore be considered for the treatment of HTPs in clinical practice. However, caution and close monitoring are recommended, owing to the absence of long-term safety data and the potential risks posed by prolonged bone marrow stimulation in certain HTPs. In this review, we summarize the available clinical data on TPO-RAs in the treatment of HTPs, and discuss their use in patients with these disorders. We believe that TPO-RAs will play a major role in the treatment of HTPs, particularly myosin heavy chain 9-related disease, Wiskott-Aldrich syndrome, X-linked thrombocytopenia, and thrombocytopenia caused by THPO mutations.

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Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial

Abstract: Associazione QOL-ONE.

Cited by 144 publications

References 28 publications

How we manage adults with myelodysplastic syndrome

How we manage adults with myelodysplastic syndrome

Myelodysplastic syndromes: 2018 update on diagnosis, risk‐stratification and management

Thrombopoietin receptor agonists in hereditary thrombocytopenias

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