Tamibarotene appears to show some clinical activity among patients with relapsed/refractory acute myeloid leukemia (AML) with evidence of RARA overexpression, according to phase 2 trial research published in Leukemia and Lymphoma. The authors suggested that the findings support the investigation of tamibarotene in combination with other treatments in this setting.

RARA is overexpressed in approximately half of patients with myelodysplastic syndromes and 30% of patients with AML; the gene is, furthermore, known to be involved in myeloid differentiation, rendering it a potentially viable target in hematologic cancers.

Tamibarotene is a selective, orally administered agonist of RAR-alpha, a ligand-regulated nuclear receptor encoded by RARA, and has shown promise in preclinical study. For this phase 2 trial, researchers evaluated the safety and efficacy of tamibarotene among patients with relapsed/refractory AML with RARA overexpression.

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Overall, of 94 patients screened, 28 were enrolled to the study and 21 had evaluable response data. At baseline, among enrolled patients, the median age was 74 years (range, 30-87), 46% of patients were male sex, 46% of patients had de novo AML, and 54% had baseline bone marrow blasts of 30% or less.

Analysis showed that the overall response rate was 19%, which included complete remissions (5%) and complete remissions with incomplete blood count recovery (14%). The time to first response was 1.2 months; the median duration of response was 6 months.

The median overall survival period was 5.9 months (95% CI, 2.7-11). Grade 3 or worse adverse events included febrile neutropenia (39%), hypertriglyceridemia (21%), and arthralgia (7%).

“The favorable safety profile and preliminary clinical activity support the development of combination therapies with tamibarotene in myeloid malignancies with RARA overexpression,” the authors wrote.

Disclosures: This research was supported by Syros Pharmaceuticals, Inc. Please see the original reference for a full list of disclosures.


Stein EM, de Botton S, Cluzeau T, et al. Use of tamibarotene, a potent and selective RARα agonist, in combination with azacitidine in patients with relapsed and refractory AML with RARA gene overexpression. Leuk Lymphoma. Published online August 12, 2023. doi:10.1080/10428194.2023.2243356