Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression
Year: 2023
Type: article
Study design: Clinical Trial
Abstract: Tamibarotene-based therapy is a novel targeted approach for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with retinoic acid receptor alpha (RARA) gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for RARA overexpression using a blood-based biomarker test that measures RARA expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with RARA overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and RARA overexpression treated with tamibarotene in combination with azacitidine, the median overall survival was 5.9 months. In 21 response-evaluable patients, the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 19%, and median time to initial CR/CRi was 1.2 months. The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression.
Authors: Eytan M. Stein, Stephane de Botton, Thomas Cluzeau, Arnaud Pigneux, Jane L. Liesveld, Rachel J. Cook, Philippe Rousselot, David A. Rizzieri, Thorsten Braun, Gail J. Roboz, Delphine Lebon, Mael Heiblig, Kristen Baker, Angela Volkert, Sofia Paul, Nisha Rajagopal, David A. Roth, Michael Kelly, Pierre Peterlin
Institutions: Memorial Sloan Kettering Cancer Center, Institut Gustave Roussy, Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, Université de Bordeaux, Centre Hospitalier Universitaire de Bordeaux, University of Rochester Medicine, University of Rochester, Oregon Health & Science University, Université Paris-Saclay, Centre Hospitalier de Versailles, Novant Health, Hôpital Avicenne, NewYork–Presbyterian Hospital, Weill Cornell Medicine, Centre Hospitalier Universitaire Amiens-Picardie, Hôpital Lyon Sud, Syros Pharmaceuticals (United States), Centre Hospitalier Universitaire de Nantes, Nantes Université
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4385780217