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Retinoid Shows Promising Responses in Non-APL Acute Myeloid Leukemia

SAN DIEGO—A synthetic retinoid has shown promising adjunctive activity in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) in a small phase II open label study reported at the 2018 ASH Annual Meeting (Abstract 2735). The study explored the activity of SY-1425 (tamibarotene)—an oral selective agonist of retinoic acid receptor alpha (RARA) in combination with the hypomethylating agent azacitidine or the anti-CD38 antibody daratumumab (better known as a treatment for multiple myeloma) in patients with newly diagnosed AML, or relapsed/refractory AML, or higher-risk MDS. Patients with high concentrations of RARA were analyzed separately from those with and RARA-low cell lines. Since SY-1425 increases expression of CD38 molecule on leukemic cells, the hypothesis was that it could synergize with the anti-CD38 activity of daratumumab. The study found promising activity in patients who were positive for the biomarker—RARA pathway activation—and who were treated with the combination of SY-1425 with daratumumab. “It’s exciting. It’s something that’s new and different. It appears to be relatively nontoxic and we’re seeing some nice responses. It makes me feel optimistic about the future for leukemia patients,” said Rachel Cook, MD, Assistant Professor in the Leukemia Section at Oregon Health and Sciences University in Portland.