tamibarotene + azacitidine

Tamibarotene + azacitidine is a **combination therapy** under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) characterized by *retinoic acid receptor alpha* (RARA) gene overexpression. **Tamibarotene** is an orally administered, potent and selective RARα agonist that induces differentiation and antiproliferative effects in RARA-high leukemic cells, while **azacitidine** is a hypomethylating agent that inhibits DNA methyltransferase, inducing cytotoxicity in abnormal hematopoietic cells. The combination is designed to provide a targeted approach by leveraging tamibarotene's activity in RARA-overexpressing cells, which are identified using a blood-based biomarker test for RARA mRNA, and enhancing the anti-leukemic effects with azacitidine. Synergy between the two agents has been demonstrated in preclinical RARA-high AML models. This regimen has shown promising efficacy in phase 2 and 3 trials and received FDA Fast Track designation for RARA-positive AML and MDS, with a favorable safety profile and no increased myelosuppression compared to azacitidine monotherapy[1][2][4][6].