Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS
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 i...
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Elsevier
2025-08-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952925002721 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Amy E. DeZern |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-43bf4370859d4a1782efd5aa316eb5aa |
| institution | DOAJ |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-43bf4370859d4a1782efd5aa316eb5aa2025-08-20T03:02:45ZengElsevierBlood Advances2473-95292025-08-019164090409910.1182/bloodadvances.2025016229Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDSAmy E. DeZern0Sylvain Thepot1Stephane de Botton2Andrea Patriarca3Dries Deeren4Jose-Miguel Torregrossa-Diaz5Giovanni Marconi6Teresa Bernal7Juan Bergua Burgues8Blanca Xicoy9Anna Jonášová10Amer M. Zeidan11Sophie Dimicoli-Salazar12Célestine Simand13David Valcarcel14Maria Diez Campelo15Wanxing Chai-Ho16Lalit Saini17Alice Garnier18Klaus Geissler19Yishai Ofran20Zsolt Nagy21Pramila Krishnamurthy22Michael Lübbert23Grzegorz Basak24Hetty E. Carraway25David A. Sallman26Uma Borate27Valeria Santini28Victoria Campbell29Pierre Fenaux30Thorsten Braun31Francesco Lanza32Jan Maciej Zaucha33David A. Roth34Sofia Paul35Pourab Roy36Michael J. Kelly37Angela Volkert38Jaime Chisholm39Tanya Abdul Malak40Virginia M. Klimek41Thomas Cluzeau42Johns Hopkins University, Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Correspondence: Amy E. DeZern, Hematologic Malignancies, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans St, CRBI Room 2M08, Baltimore, MD 21287;Centre Hospitalier Universitaire, Hematology, Angers, FranceInstitut Gustave Roussy, Department of Hematology, Villejuif, FranceHematology Unit, AOU Maggiore della Carità and University of Eastern Piedmont, Novara, ItalyAZ Delta, Department of Hematology, Roeselare, BelgiumCentre Hospitalier Universitaire de Poitiers, University Hospital of Poitiers, Department of Hematology, Poitiers, FranceRomagnolo Institute to Study Tumors “Dino Amadori,” Department of Hematology, Meldola, ItalyHospital Universitario Central de Asturias, Department of Hematology, Oviedo, SpainHospital San Pedro de Alcántara, Department of Hematology, Caceres, SpainInstitut Català d'Oncologia, Hospital Germans Trias i Pujol, Josep Carreras Deparment of Leukemia Research Institute, Universitat Autònoma de Barcelona, Barcelona, SpainMedical Department Hematology, Charles University General Hospital, Prague, Czech RepublicYale University and Yale Cancer Center, Division of Hematologic Maignancies, New Haven, CTHôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Hematology, Bordeaux, FranceInstitut de Cancérologie de Strasbourg Europe, Hematology, Strasbourg, FranceHospital Universitario Vall d'Hebron, Department of Hematology, Barcelona, SpainHospital Universitario de Salamanca, Institute of Biomedical Research of Salamanca, Salamanca, SpainDivision of Hematology and Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CADivision of Hematology, Department of Medicine, London Health Sciences Centre, London, ON, CanadaHematology Clinic, Nantes University Hospital, Nantes, FranceHospital Hietzing, Vienna, AustriaDepartment of Hematology, Shaarei Zedek Medical Center, Jerusalem, IsraelDepartment of Internal Medicine and Hematology, Semmelweis University, Budapest, HungaryDepartment of Haematological Medicine, King’s College Hospital, London, United KingdomUniversity of Freiburg Medical Center, Freiburg, GermanyMedical University of Warsaw, Warsaw, PolandLeukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OHMoffitt Cancer Center and Research Institute, Department of Malignant Hematology, Tampa, FLLeukemia and Hematologic Malignancies Program, The Ohio State University, Columbus, OHMDS Unit, Department of Medical Sciences and Public Health, AOU Careggi, University of Florence, Firenze, ItalyLothian Health Board Western General Hospital in National Health Service Lothian, Edinburgh, ScotlandDépartement d’Hématologie et Immunologie, Assistance Publique–Hôpitaux de Paris Nord Service d'Hématologie Seniors Hôpital St Louis/Université de Paris, Paris, FranceHôpital Avicenne, Assistance Publique–Hôpitaux de Paris Service Hématologie, Paris, FranceOspedale Santa Maria delle Croci, Hematology, Ravenna, ItalyDepartment of Haematology and Transplantology, Medical University of Gdańsk University Clinical Center, Gdańsk, PolandSyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MASyros Pharmaceuticals, Inc, Cambridge, MACentre Hospitalier Universitaire de Nice, Nice, FranceAbstract: 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.http://www.sciencedirect.com/science/article/pii/S2473952925002721 |
| spellingShingle | 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 Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS Blood Advances |
| title | Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS |
| title_full | Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS |
| title_fullStr | Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS |
| title_full_unstemmed | Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS |
| title_short | Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS |
| title_sort | pivotal results of select mds 1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher risk mds |
| url | http://www.sciencedirect.com/science/article/pii/S2473952925002721 |
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