Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS)
Year: 2023
Type: article
Study design: Clinical Trial
Abstract: PURPOSE In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with poor prognosis. This multicenter trial presents the second-part long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thrombocytopenia. METHODS In this single-blind, randomized, placebo-controlled, phase-II trial of adult patients with International Prognostic Scoring System low- or intermediate-1-risk MDS, patients with a stable platelet (PLT) count (<30 × 103/mm3) received eltrombopag or placebo until disease progression. Primary end points were duration of PLT response (PLT-R; calculated from the time of PLT-R to date of loss of PLT-R, defined as bleeding/PLT count <30 × 103/mm3 or last date in observation) and long-term safety and tolerability. Secondary end points included incidence and severity of bleeding, PLT transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival and pharmacokinetics. RESULTS From 2011 to 2021, of 325 patients screened, 169 patients were randomly assigned oral eltrombopag (N = 112) or placebo (N = 57) at a starting dose of 50 mg once daily to maximum of 300 mg. PLT-R, with 25-week follow-up (IQR, 14-68) occurred in 47/111 (42.3%) eltrombopag patients versus 6/54 (11.1%) in placebo (odds ratio, 5.9; 95% CI, 2.3 to 14.9; P < .001). In eltrombopag patients, 12/47 (25.5%) lost the PLT-R, with cumulative thrombocytopenia relapse-free survival at 60 months of 63.6% (95% CI, 46.0 to 81.2). Clinically significant bleeding (WHO bleeding score ≥ 2) occurred less frequently in the eltrombopag arm than in the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). Although no difference in the frequency of grade 1-2 adverse events (AEs) was observed, a higher proportion of eltrombopag patients experienced grade 3-4 AEs (χ2 = 9.5, P = .002). AML evolution and/or disease progression occurred in 17% (for both) of eltrombopag and placebo patients with no difference in survival times. CONCLUSION Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov identifier: NCT02912208 and EU Clinical Trials Register: EudraCT No. 2010-022890-33.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.22.02699
Authors: Esther Natalie Oliva, Marta Riva, Pasquale Niscola, Valeria Santini, Massimo Breccia, Valentina Giai, Antonella Poloni, Andrea Patriarca, Elena Crisà, Isabella Capodanno, Prassede Salutari, Gianluigi Reda, Nicola Cascavilla, Dario Ferrero, Attilio Guarini, Giovanni Tripepi, Giuseppe Iannì, Emilio Russo, Andrea Castelli, Bruno Fattizzo, Germana Beltrami, Monica Bocchia, Alfredo Molteni, Pierre Fenaux, Ulrich Germing, Alessandra Ricco, Giuseppe A. Palumbo, Stefana Impera, Nicola Di Renzo, Flavia Rivellini, Francesco Buccisano, Aspasia Stamatoullas-Bastard, Anna Marina Liberati, Anna Candoni, Ilaria Maria Delfino, Maria Teresa Arcadi, Patrizia Cufari, Lorenzo Rizzo, Irene Bova, Maria Grazia D'Errigo, Gina Zini, Roberto Latagliata
Institutions: Azienda ospedaliera "Bianchi-Melacrino-Morelli", Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, St. Eugenio Hospital, Azienda Ospedaliero-Universitaria Careggi, Policlinico Umberto I, Sapienza University of Rome, Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo, Azienda Ospedaliero-Universitaria delle Marche, Azienda Ospedaliero Universitaria Maggiore della Carita, Candiolo Cancer Institute, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Casa Sollievo della Sofferenza, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Turin, Istituto Tumori Bari, Istituto di Fisiologia Clinica, National Research Council, Ospedale degli Infermi, University of Milan, Ospedale Policlinico San Martino, University of Siena, Azienda Ospedaliera Universitaria Senese, Azienda Socio Sanitaria Territoriale di Cremona, Groupe Francophone des Myélodysplasies, Heinrich Heine University Düsseldorf, Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari, University of Catania, Ospedale Garibaldi, Ospedale Vito Fazzi, Azienda Sanitaria Locale Salerno, University of Rome Tor Vergata, Policlinico Tor Vergata, Centre Henri Becquerel, University of Perugia, University of Udine, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Ospedale di Belcolle
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funder: Celgene
OpenAlex ID: W4379980418