Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS

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.

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Publication Details

Journal
Blood Advances
Published
2025-05-07
DOI
https://doi.org/10.1182/bloodadvances.2025016229
Citations
6
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
10.62

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article

Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS

Thorsten Braun, Jan Maciej Zaucha, Lalit Saini, Pramila Krishnamurthy et al.
6 citations
Blood Advances
Acute Myeloid Leukemia Research
10.62
article

Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS

Thorsten Braun, Jan Maciej Zaucha, Lalit Saini, Pramila Krishnamurthy, Sylvain Thépot, John C. Chisolm, Uma Borate, Pierre Fenaux, Hetty E. Carraway, Stéphane de Botton, Sophie Dimicoli‐Salazar, David Valcárcel, Victoria Campbell, Francesco Lanza, Giovanni Marconi, Andrea Patriarca, David Andrew Sallman, Yishai Ofran, David A. Roth, Amy Elizabeth Dezern, Alice Garnier, Anna Jonášová, Virginia M. Klimek, Michael Lübbert, Grzegorz Władysław Basak, Dries Deeren, Pourab Roy, José Miguel Torregrosa Diaz, María Díez‐Campelo, Célestine Simand, Blanca Xicoy, Amer Methqal Zeidan, Wanxing Chai‐Ho, Juan Bergua, Teresa Bernal, Klaus Geißler, Thomas Cluzeau, Zsolt Nagy, Valeria Santini, Tanya Abdul Malak, Michael Kelly, Angela Volkert, Sofia Paul
article en
6 citations

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.

Blood AdvancesVol. 9(16)
Semmelweis University (HU), Sigmund Freud Privatuniversität Wien (AT), Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT), Cleveland Clinic (US), NHS Lothian (GB), Université de Bordeaux (FR), University of Freiburg (DE), University of California, Los Angeles (US), Universidad de Salamanca (ES), Université Paris Cité (FR), Charles University (CZ), Medical University of Warsaw (PL), Western General Hospital (GB), London Health Sciences Centre (CA), University Medical Center Freiburg (DE), UCLA Medical Center (US), Institut Gustave Roussy (FR), Shaare Zedek Medical Center (IL), Yale Cancer Center (US), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Nice (FR), Centre Hospitalier Universitaire de Nantes (FR), Moffitt Cancer Center (US), Yale University (US), Institut de génétique et de biologie moléculaire et cellulaire (FR), Klinik Hietzing (AT), Josep Carreras Leukaemia Research Institute (ES), Institut de Cancérologie Strasbourg (FR), Sorbonne Paris Cité (FR), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Assistance Publique – Hôpitaux de Paris (FR), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Complejo Hospitalario de Salamanca (ES), Institut Català d'Oncologia (ES), Laboratoire de Thermique et Energie de Nantes (FR), Centre Hospitalier Universitaire de Poitiers (FR), Hospital San Pedro de Alcántara (ES), Centre Hospitalier Universitaire d'Angers (FR), Azienda Ospedaliero-Universitaria Careggi (IT), Vall d'Hebron Hospital Universitari (ES), Hospital Universitario Central de Asturias (ES), Instituto de Investigación Biomédica de Salamanca (ES), AZ Delta (BE), Hôpital Saint-Louis (FR), Istituti di Ricovero e Cura a Carattere Scientifico (IT), King's College Hospital (GB), Piedmont University (US), Synta Pharmaceuticals (United States) (US), General University Hospital in Prague (CZ), Sidney Kimmel Comprehensive Cancer Center (US), University of Florence (IT), University of Warsaw (PL), The Ohio State University (US), Gdańsk Medical University (PL), Nantes Université (FR)
Amgen, Pfizer, Sanofi, Gilead Sciences, Celgene, Astex Pharmaceuticals, Agios Pharmaceuticals, bluebird bio, BeiGene, Incyte, Syndax Pharmaceuticals, Astellas Pharma, Servier, Swedish Orphan Biovitrum, Genentech, Daiichi Sankyo Europe
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Openalex Percentile: Top 2%
Acute Myeloid Leukemia Research
10.62
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