Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with gene overexpression.

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 () gene overexpression. Approximately, 50% of higher-risk myelodysplastic syndrome (MDS) patients and approximately 30% of AML patients are positive for overexpression using a blood-based biomarker test that measures expression in peripheral blasts. A phase 2 study investigating the activity of tamibarotene in patients with overexpression was conducted in patients with AML and MDS (NCT02807558). In 28 patients with R/R AML and 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 overexpression.