PMID- 37294914 OWN - NLM STAT- MEDLINE DCOM- 20231007 LR - 20231024 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 41 IP - 28 DP - 2023 Oct 1 TI - Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS). PG - 4486-4496 LID - 10.1200/JCO.22.02699 [doi] AB - 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 x 10(3)/mm(3)) 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 x 10(3)/mm(3) 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 (chi(2) = 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. FAU - Oliva, Esther Natalie AU - Oliva EN AUID- ORCID: 0000-0001-9238-5734 AD - U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy. FAU - Riva, Marta AU - Riva M AD - Dipartimento di Ematologia, Ospedale Niguarda Ca' Granda, Milano, Italy. FAU - Niscola, Pasquale AU - Niscola P AD - U.O. di Ematologia, Ospedale Sant'Eugenio, Roma, Italy. FAU - Santini, Valeria AU - Santini V AUID- ORCID: 0000-0002-5439-2172 AD - U.O. di Ematologia, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy. FAU - Breccia, Massimo AU - Breccia M AD - Dipartimento di Ematologia Policlinico Umberto I, Universita La Sapienza, Roma, Italy. FAU - Giai, Valentina AU - Giai V AD - S.C. a Direzione Universitaria di Ematologia A.O., SS. Antonio e Biagio e Cesare Arrigo Alessandria, Alessandria, Italy. FAU - Poloni, Antonella AU - Poloni A AD - Clinica di Ematologia Azienda Ospedaliera Universitaria-Ospedali Riuniti di Ancona, Ancona, Italy. FAU - Patriarca, Andrea AU - Patriarca A AUID- ORCID: 0000-0003-4415-2906 AD - AOU Maggiore della Carita, Novara, Italy. FAU - Crisa, Elena AU - Crisa E AUID- ORCID: 0000-0003-1912-0574 AD - Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy. FAU - Capodanno, Isabella AU - Capodanno I AD - U.O. di Ematologia, A.U.S.L.-IRCCS di Reggio Emilia, Reggio Emilia, Italy. FAU - Salutari, Prassede AU - Salutari P AD - Dipartimento Oncologico-Ematologico, Ospedale Civile Spirito Santo, Pescara, Italy. FAU - Reda, Gianluigi AU - Reda G AUID- ORCID: 0000-0003-4687-7089 AD - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. FAU - Cascavilla, Nicola AU - Cascavilla N AD - U.O. Ematologia Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. FAU - Ferrero, Dario AU - Ferrero D AD - Dipartimento Biotecnologie Molecolari, Ematologia Universitaria A.O.U. Citta' della Salute e della Scienza di Torino, Turin, Italy. FAU - Guarini, Attilio AU - Guarini A AD - U.O. Ematologia I.R.C.C.S. Istituto Tumori "Giovanni Paolo II", Bari, Italy. FAU - Tripepi, Giovanni AU - Tripepi G AUID- ORCID: 0000-0002-3580-4602 AD - IFC-CNR Institute of Clinical Physiology, Reggio Calabria, Italy. FAU - Ianni, Giuseppe AU - Ianni G AD - Dielnet SRL-CRO Reggio Calabria, Reggio Calabria, Italy. FAU - Russo, Emilio AU - Russo E AUID- ORCID: 0000-0002-1279-8123 AD - Department of Pharmacology, University of Germaneto Catanzaro, Catanzaro, Italy. FAU - Castelli, Andrea AU - Castelli A AUID- ORCID: 0000-0002-4972-120X AD - SSD Ematologia Ospedale degli Infermi, Biella, Italy. FAU - Fattizzo, Bruno AU - Fattizzo B AUID- ORCID: 0000-0003-0857-8379 AD - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. AD - Dipartimento di Oncologia ed Emato-Oncologia, Universita degli Studi di Milano, Milan, Italy. FAU - Beltrami, Germana AU - Beltrami G AD - U.O. Ematologia e terapie cellulari, IRCCS Azienda Ospedaliera Universitaria San Martino, Genova, Italy. FAU - Bocchia, Monica AU - Bocchia M AUID- ORCID: 0000-0003-3538-3913 AD - UOC Ematologia, Universita di Siena, Azienda Ospedaliera Universitaria Senese, Siena, Italy. FAU - Molteni, Alfredo AU - Molteni A AD - Divisione di Ematologia, ASST di Cremona, Cremona, Italy. FAU - Fenaux, Pierre AU - Fenaux P AD - Groupe Francais desmyelodysplasies (GFM), Paris, France. FAU - Germing, Ulrich AU - Germing U AD - Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University Dusseldorf, Dusseldorf, Germany. FAU - Ricco, Alessandra AU - Ricco A AD - U.O. Ematologia con Trapianto, Azienda Ospedale Policlinicodi Bari, Bari, Italy. FAU - Palumbo, Giuseppe A AU - Palumbo GA AUID- ORCID: 0000-0003-1859-6319 AD - Dipartimento di Scienze Mediche Chirurgiche e Tecnologie Avanzate "G.F. Ingrassia", University of Catania, Catania, Italy. FAU - Impera, Stefana AU - Impera S AD - U.O. C. Ematologia, A. O.ad Alta Specializzazione Ospedale Garibaldi Nesima, Catania, Italy. FAU - Di Renzo, Nicola AU - Di Renzo N AD - U.O. di Ematologia, Ospedale Vito Fazzi, Lecce, Italy. FAU - Rivellini, Flavia AU - Rivellini F AD - Divisione Ematologia, P.O. A. Tortora di Pagani-ASL Salerno, Pagani, Italy. FAU - Buccisano, Francesco AU - Buccisano F AUID- ORCID: 0000-0003-4320-9253 AD - Divisione di Biopatologia e Diagnostica per Immagini, Policlinico Universitario Tor Vergata, Rome, Italy. FAU - Stamatoullas-Bastard, Aspasia AU - Stamatoullas-Bastard A AUID- ORCID: 0000-0001-7321-5254 AD - Centre Henri Becquerel, Rue d'Amiens, Rouen, France. FAU - Liberati, Anna Marina AU - Liberati AM AD - S.C. Oncoematologia, Universita degli Studi di Perugia A.O. Santa Maria, Terni, Italy. FAU - Candoni, Anna AU - Candoni A AD - Divisione Ematologia, P.O. Santa Maria della Misericordia, A.S.U.F.C di Udine, Udine, Italy. FAU - Delfino, Ilaria Maria AU - Delfino IM AD - U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy. FAU - Arcadi, Maria Teresa AU - Arcadi MT AD - U.O. Farmacia Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy. FAU - Cufari, Patrizia AU - Cufari P AD - U.O.C. Ematologia, Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy. FAU - Rizzo, Lorenzo AU - Rizzo L AUID- ORCID: 0000-0002-8778-8317 AD - Dipartimento di Ematologia, Ospedale Niguarda Ca' Granda, Milan, Italy. FAU - Bova, Irene AU - Bova I AD - U.O.S. di Genetica Medica Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy. FAU - D'Errigo, Maria Grazia AU - D'Errigo MG AD - U.O.S. di Genetica Medica Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Reggio di Calabria, Italy. FAU - Zini, Gina AU - Zini G AUID- ORCID: 0000-0003-0782-294X AD - Fondazione Policlinico, Universitario A. Gemelli IRCCS, Rome, Italy. AD - Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Latagliata, Roberto AU - Latagliata R AD - Divisione di Ematologia, Ospedale Belcolle, Viterbo, Italy. LA - eng SI - ClinicalTrials.gov/NCT02912208 SI - EudraCT/2010-022890-33 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230609 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - S56D65XJ9G (eltrombopag) RN - 0 (Hydrazines) SB - IM CIN - J Clin Oncol. 2023 Oct 1;41(28):4465-4468. PMID: 37428990 MH - Adult MH - Humans MH - Disease Progression MH - Hemorrhage/chemically induced/complications/drug therapy MH - *Hydrazines/adverse effects/therapeutic use MH - *Myelodysplastic Syndromes/complications/drug therapy MH - Neoplasm Recurrence, Local/drug therapy MH - Quality of Life MH - Single-Blind Method MH - *Thrombocytopenia/complications/drug therapy PMC - PMC10552995 COIS- The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to http://www.asco.org/rwc or https://ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Esther Natalie Oliva Honoraria: Celgene, Novartis, Amgen, Alexion Pharmaceuticals, Daiichi Sankyo Europe GmbH, SOBI, Servier, Janssen Consulting or Advisory Role: Amgen, Celgene, Novartis, Janssen, Daiichi Sankyo, Alexion Pharmaceuticals Speakers' Bureau: Celgene, Novartis, Amgen Patents, Royalties, Other Intellectual Property: Royalties for QOL-E instrument, Royalties for HM-PRO Valeria Santini Honoraria: Celgene/Bristol Myers Squibb, Novartis Consulting or Advisory Role: Celgene/Bristol Myers Squibb, Novartis, Menarini, Gilead Sciences, AbbVie, Syros Pharmaceuticals, Servier, Geron, CTI, Otsuka Research Funding: Celgene (Inst) Travel, Accommodations, Expenses: Janssen-Cilag, Celgene Massimo Breccia Honoraria: Novartis, Incyte Valentina Giai Consulting or Advisory Role: Alexion Pharmaceuticals, Incyte, Novartis Andrea Patriarca Consulting or Advisory Role: Sanofi, SOBI Speakers' Bureau: Novartis Italy, Incyte Dario Ferrero Research Funding: PPD Global (Inst) Emilio Russo Honoraria: Jazz Pharmaceuticals, GW Pharmaceuticals Consulting or Advisory Role: Angelini Pharma S.P.A, Jazz Pharmaceuticals, GW Pharmaceuticals, Eisai Speakers' Bureau: GW Pharmaceuticals, Angelini Pharma S.P.A, Jazz Pharmaceuticals, Eisai, UCB Research Funding: GW Pharmaceuticals, Kolfarma Srl Travel, Accommodations, Expenses: Angelini Pharma S.P.A Andrea Castelli Travel, Accommodations, Expenses: Novartis Italy, Incyte Bruno Fattizzo Consulting or Advisory Role: Janssen, SOBI, Alexion Pharmaceuticals, Samsung Bioepis, Annexon Biosciences Speakers' Bureau: Novartis, SOBI, Alexion Pharmaceuticals, Apellis Pharmaceuticals Research Funding: Agios Monica Bocchia Travel, Accommodations, Expenses: Incyte, Janssen, AbbVie Alfredo Molteni Consulting or Advisory Role: AbbVie Pierre Fenaux Honoraria: Bristol Myers Squibb Consulting or Advisory Role: Bristol Myers Squibb Research Funding: Bristol Myers Squibb Ulrich Germing Honoraria: Celgene, Novartis, Jazz Pharmaceuticals Consulting or Advisory Role: Celgene Research Funding: Celgene (Inst), Novartis (Inst) Alessandra Ricco Consulting or Advisory Role: Alexion Pharmaceuticals, SOBI, Novartis Speakers' Bureau: Novartis Travel, Accommodations, Expenses: Novartis, SOBI Giuseppe A. Palumbo Consulting or Advisory Role: Novartis, AOP Orphan Pharmaceuticals, AbbVie, AstraZeneca, Celgene/Bristol Myers Squibb, GlaxoSmithKline Speakers' Bureau: Novartis, Celgene/Bristol Myers Squibb, AbbVie Travel, Accommodations, Expenses: Takeda, Novartis Francesco Buccisano Consulting or Advisory Role: AbbVie, Jazz Pharmaceuticals Speakers' Bureau: Novartis Aspasia Stamatoullas-Bastard Consulting or Advisory Role: Pfizer, Janssen Travel, Accommodations, Expenses: Pfizer Anna Marina Liberati Consulting or Advisory Role: Servier Research Funding: Novartis (Inst), Janssen-Cilag (Inst), AbbVie (Inst), Roche (Inst), Amgen (Inst), Sanofi (Inst), Celgene (Inst), Bristol Myers Squibb (Inst), Takeda (Inst), Incyte (Inst), Beigene (Inst), Oncopeptides (Inst), Verastem (Inst), Karyopharm Therapeutics (Inst), Archigen Biotech (Inst), Debiopharm Group (Inst), MorphoSys (Inst), FibroGen (Inst), Onconova Therapeutics (Inst), Loxo (Inst) Travel, Accommodations, Expenses: Bristol Myers Squibb, Sanofi, Takeda, Roche, Celgene, Novartis, AbbVie, IQvia, Verastem No other potential conflicts of interest were reported. EDAT- 2023/06/09 19:42 MHDA- 2023/09/29 06:43 PMCR- 2023/06/09 CRDT- 2023/06/09 16:03 PHST- 2023/09/29 06:43 [medline] PHST- 2023/06/09 19:42 [pubmed] PHST- 2023/06/09 16:03 [entrez] PHST- 2023/06/09 00:00 [pmc-release] AID - JCO.22.02699 [pii] AID - 10.1200/JCO.22.02699 [doi] PST - ppublish SO - J Clin Oncol. 2023 Oct 1;41(28):4486-4496. doi: 10.1200/JCO.22.02699. Epub 2023 Jun 9.