Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: Higher-risk myelodysplastic syndrome (HR-MDS) with RARA gene overexpression is a subset of patients (pts) with an actionable target for tamibarotene, an oral and a selective retinoic acid receptor-α (RAR-α) agonist. Tamibarotene with azacitidine (AZA) showed complete remission (CR) rates in myeloid leukemia. SELECT-MDS-1 was a phase 3 study comparing the activity of tamibarotene + AZA to placebo + AZA in these pts with newly diagnosed HR-MDS with RARA overexpression. Eligible pts had confirmed RARA overexpression, untreated MDS with higher-risk features by revised International Prognostic Scoring System (IPSS-R), and marrow blast count >5%. Pts were randomized 2:1 to receive tamibarotene + AZA or placebo + AZA, respectively. A total of 246 participants were randomized with 164 and 82 in the tamibarotene + AZA and placebo + AZA groups, respectively. Baseline characteristics included: 69.9% male; median age 75 years (range, 38-93); primary MDS, 89.8%; MDS-excess blasts-1, 48% and MDS-excess blasts-2, 52%; and IPSS-R risk category intermediate (25.5%), high (35.7%), and very high (38.9%). The study did not meet the primary end point of CR, with a P value of .2084 for the treatment effect in the tamibarotene + AZA group. The CR rates were 23.81% and 18.75% in the tamibarotene + AZA and placebo + AZA groups, respectively. The use of tamibarotene-based therapy to target RAR-α as a novel approach in pts with HR-MDS with RARA gene overexpression is not a paradigm, which can augment response rates beyond AZA monotherapy. Further explorations of alternative approaches, including those with a biomarker, to alter the natural history of this disease are warranted. This trial was registered at www.clinicaltrials.gov as #NCT04797780.
Source: Blood Advances
Authors: Amy E. DeZern, Sylvain Thepot, Stephane de Botton, Andrea Patriarca, Dries Deeren, Jose-Miguel Torregrossa-Diaz, Giovanni Marconi, Teresa Bernal, Juan Bergua Burgues, Blanca Xicoy, Anna Jonášová, Amer M. Zeidan, Sophie Dimicoli-Salazar, Célestine Simand, David Valcarcel, Maria Diez Campelo, Wanxing Chai-Ho, Lalit Saini, Alice Garnier, Klaus Geissler, Yishai Ofran, Zsolt Nagy, Pramila Krishnamurthy, Michael Lübbert, Grzegorz Basak, Hetty E. Carraway, David A. Sallman, Uma Borate, Valeria Santini, Victoria Campbell, Pierre Fenaux, Thorsten Braun, Francesco Lanza, Jan Maciej Zaucha, David A. Roth, Sofia Paul, Pourab Roy, Michael J. Kelly, Angela Volkert, Jaime Chisholm, Tanya Abdul Malak, Virginia M. Klimek, Thomas Cluzeau
Institutions: Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Centre Hospitalier Universitaire d'Angers, Institut Gustave Roussy, Università degli Studi del Piemonte Orientale “Amedeo Avogadro”, Azienda Ospedaliero Universitaria Maggiore della Carita, AZ Delta, Centre Hospitalier Universitaire de Poitiers, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Hospital Universitario Central de Asturias, Hospital San Pedro de Alcántara, Universitat Autònoma de Barcelona, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia, Charles University, Yale Cancer Center, Yale University, Centre Hospitalier Universitaire de Bordeaux, Institut de génétique et de biologie moléculaire et cellulaire, Institut de Cancérologie Strasbourg, Vall d'Hebron Hospital Universitari, Complejo Hospitalario de Salamanca, Instituto de Investigación Biomédica de Salamanca, University of California, Los Angeles, Ronald Reagan UCLA Medical Center, UCLA Medical Center, London Health Sciences Centre, Centre Hospitalier Universitaire de Nantes, Nantes Université, Sigmund Freud Privatuniversität Wien, Klinik Hietzing, Hebrew University of Jerusalem, Shaare Zedek Medical Center, Bikur Cholim Hospital, Semmelweis University, King's College London, King's College Hospital, University of Freiburg, University Medical Center Freiburg, Medical University of Warsaw, Cleveland Clinic, Moffitt Cancer Center, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Azienda Ospedaliero-Universitaria Careggi, University of Florence, National Health Service, Western General Hospital, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Recherche clinique appliquée à l'hématologie, Institut de recherche Saint-Louis, Laboratoire d'hématologie, Ospedale "Santa Maria delle Croci" di Ravenna, University of Bologna, University Clinical Centre, Gdańsk Medical University, Syros Pharmaceuticals (United States), Université Côte d'Azur, Centre Hospitalier Universitaire de Nice
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W4410140459