Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS).
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Oliva Esther Natalie, Riva Marta, Niscola Pasquale, Santini Valeria, Breccia Massimo, Giai Valentina, Poloni Antonella, Patriarca Andrea, Crisà Elena, Capodanno Isabella, Salutari Prassede, Reda Gianluigi, Cascavilla Nicola, Ferrero Dario, Guarini Attilio, Tripepi Giovanni, Iannì Giuseppe, Russo Emilio, Castelli Andrea, Fattizzo Bruno, Beltrami Germana, Bocchia Monica, Molteni Alfredo, Fenaux Pierre, Germing Ulrich, Ricco Alessandra, Palumbo Giuseppe A, Impera Stefana, Di Renzo Nicola, Rivellini Flavia, Buccisano Francesco, Stamatoullas-Bastard Aspasia, Liberati Anna Marina, Candoni Anna, Delfino Ilaria Maria, Arcadi Maria Teresa, Cufari Patrizia, Rizzo Lorenzo, Bova Irene, D'Errigo Maria Grazia, Zini Gina, Latagliata Roberto
Аннотация
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.