Fiche publication
Date publication
août 2025
Journal
Blood advances
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SIMAND Célestine
Tous les auteurs :
DeZern AE, Thepot S, de Botton S, Patriarca A, Deeren D, Torregrossa-Diaz JM, Marconi G, Bernal T, Bergua Burgues J, Xicoy B, Jonášová A, Zeidan AM, Dimicoli-Salazar S, Simand C, Valcarcel D, Diez Campelo M, Chai-Ho W, Saini L, Garnier A, Geissler K, Ofran Y, Nagy Z, Krishnamurthy P, Lübbert M, Basak G, Carraway HE, Sallman DA, Borate U, Santini V, Campbell V, Fenaux P, Braun T, Lanza F, Zaucha JM, Roth DA, Paul S, Roy P, Kelly MJ, Volkert A, Chisholm J, Malak TA, Klimek VM, Cluzeau T
Lien Pubmed
Résumé
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.
Mots clés
Humans, Azacitidine, administration & dosage, Male, Myelodysplastic Syndromes, drug therapy, Female, Middle Aged, Aged, Adult, Benzoates, administration & dosage, Tetrahydronaphthalenes, administration & dosage, Antineoplastic Combined Chemotherapy Protocols, therapeutic use, Treatment Outcome, Aged, 80 and over
Référence
Blood Adv. 2025 08 26;9(16):4090-4099
