Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS)

Author(s): Esther Natalie Oliva, MD1; Marta Riva, MD2; Pasquale Niscola, MD3; Valeria Santini, MD4; Massimo Breccia, MD5; Valentina Giai, MD6; Antonella Poloni, MD7; Andrea Patriarca, MD8; Elena Crisà, MD9; Isabella Capodanno, MD10; Prassede Salutari, MD11; Gianluigi Reda, MD12; Nicola Cascavilla, MD13; Dario Ferrero, MD14; Attilio Guarini, MD15; Giovanni Tripepi, PhD16; Giuseppe Iannì, BSc17; Emilio Russo, PhD18; Andrea Castelli, MD19; Bruno Fattizzo, MD12,20; Germana Beltrami, MD21; Monica Bocchia, MD22; Alfredo Molteni, MD23; Pierre Fenaux, MD24; Ulrich Germing, MD25; Alessandra Ricco, MD26; Giuseppe A. Palumbo, MD, PhD27; Stefana Impera, MD28; Nicola Di Renzo, MD29; Flavia Rivellini, MD30; Francesco Buccisano, MD31; Aspasia Stamatoullas-Bastard, MD32; Anna Marina Liberati, MD33; Anna Candoni, MD34; Ilaria Maria Delfino, BSc1; Maria Teresa Arcadi, BSc35; Patrizia Cufari, BSc1; Lorenzo Rizzo, MD36; Irene Bova, BSc37; Maria Grazia D’Errigo, BSc37; Gina Zini, MD38,39; and Roberto Latagliata, MD40
Source: DOI: 10.1200/JCO.22.02699 Journal of Clinical Oncology 41, no. 28 (October 01, 2023) 4486-4496.
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

This great Italian study uses eltrombopag in patients with low/intermediate risk MDS. The intervention arm had significantly fewer minor bleeding events and better platelet counts that were durable. Those with higher baseline Hb’s seemed to respond better to therapy, particularly if the Hb was >8g/dL. AML evolution/blast progression was not more common in the treatment arm, which refutes some prior concerns.


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.


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.


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.


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.

Author Affiliations

1U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy; 2Dipartimento di Ematologia, Ospedale Niguarda Ca’ Granda, Milano, Italy; 3U.O. di Ematologia, Ospedale Sant’Eugenio, Roma, Italy; 4U.O. di Ematologia, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy; 5Dipartimento di Ematologia Policlinico Umberto I, Università La Sapienza, Roma, Italy; 6S.C. a Direzione Universitaria di Ematologia A.O., SS. Antonio e Biagio e Cesare Arrigo Alessandria, Alessandria, Italy; 7Clinica di Ematologia Azienda Ospedaliera Universitaria—Ospedali Riuniti di Ancona, Ancona, Italy; 8AOU Maggiore della Carità, Novara, Italy; 9Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy; 10U.O. di Ematologia, A.U.S.L.-IRCCS di Reggio Emilia, Reggio Emilia, Italy; 11Dipartimento Oncologico-Ematologico, Ospedale Civile Spirito Santo, Pescara, Italy; 12Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; 13U.O. Ematologia Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; 14Dipartimento Biotecnologie Molecolari, Ematologia Universitaria A.O.U. Citta’ della Salute e della Scienza di Torino, Turin, Italy; 15U.O. Ematologia I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Bari, Italy; 16IFC-CNR Institute of Clinical Physiology, Reggio Calabria, Italy; 17Dielnet SRL—CRO Reggio Calabria, Reggio Calabria, Italy; 18Department of Pharmacology, University of Germaneto Catanzaro, Catanzaro, Italy; 19SSD Ematologia Ospedale degli Infermi, Biella, Italy; 20Dipartimento di Oncologia ed Emato-Oncologia, Università degli Studi di Milano, Milan, Italy; 21U.O. Ematologia e terapie cellulari, IRCCS Azienda Ospedaliera Universitaria San Martino, Genova, Italy; 22UOC Ematologia, Università di Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy; 23Divisione di Ematologia, ASST di Cremona, Cremona, Italy; 24Groupe Francais desmyélodysplasies (GFM), Paris, France; 25Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; 26U.O. Ematologia con Trapianto, Azienda Ospedale Policlinicodi Bari, Bari, Italy; 27Dipartimento di Scienze Mediche Chirurgiche e Tecnologie Avanzate “G.F. Ingrassia”, University of Catania, Catania, Italy; 28U.O. C. Ematologia, A. O.ad Alta Specializzazione Ospedale Garibaldi Nesima, Catania, Italy; 29U.O. di Ematologia, Ospedale Vito Fazzi, Lecce, Italy; 30Divisione Ematologia, P.O. A. Tortora di Pagani-ASL Salerno, Pagani, Italy; 31Divisione di Biopatologia e Diagnostica per Immagini, Policlinico Universitario Tor Vergata, Rome, Italy; 32Centre Henri Becquerel, Rue d’Amiens, Rouen, France; 33S.C. Oncoematologia, Università degli Studi di Perugia A.O. Santa Maria, Terni, Italy; 34Divisione Ematologia, P.O. Santa Maria della Misericordia, A.S.U.F.C di Udine, Udine, Italy; 35U.O. Farmacia Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy; 36Dipartimento di Ematologia, Ospedale Niguarda Ca’ Granda, Milan, Italy; 37U.O.S. di Genetica Medica Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy; 38Fondazione Policlinico, Universitario A. Gemelli IRCCS, Rome, Italy; 39Università Cattolica del Sacro Cuore, Rome, Italy; 40Divisione di Ematologia, Ospedale Belcolle, Viterbo, Italy

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