Dr Marconi on the Investigation of Tamibarotene Plus Azacitidine in Higher-risk MDS

Giovanni Marconi, MD, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, discusses ongoing research with the combination of tamibarotene (formerly SY-1425) and azacitidine (Vidaza) in patients with higher-risk myelodysplastic syndrome (MDS).

The oral selective retinoic acid receptor alpha (RARA) agonist tamibarotene is under investigation in patients with higher-risk MDS, with the rationale to leverage transcriptional programming instead of molecular activation in this disease, Marconi says. Tamibarotene is currently approved in Japan for patients with recurrent acute promyelocytic leukemia, and in January 2026, the FDA granted a fast-track designation to the agent in patients with higher-risk MDS.

Tamibarotene may be effective in patients with MDS because approximately 50% of patients with MDS with excessive blasts may have RARA overexpression, Marconi explains. Targeting RARA with tamibarotene may be an effective strategy for inducing remissions in this population while decreasing the risk for adverse effects such as cytopenias, Marconi emphasizes.

Previously, the phase 2 SY-1425-201 trial (NCT02807558) investigated tamibarotene in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia who were unfit for intensive chemotherapy. In this trial, the patients with RARA-positive disease had an overall response rate (ORR) of 67%, with 61% of patients achieving a complete response (CR) and 6% of patients achieving a morphologic leukemia-free state. Based on these positive results, the global, phase 3 SELECT MDS-1 trial (NCT04797780) was designed to evaluate tamibarotene plus azacitidine in patients with newly diagnosed, RARA-positive, higher-risk MDS. This trial’s primary end point is CR rate, with secondary end points including ORR, event-free survival, overall survival, and safety. SELECT MDS-1 is ongoing, and results are expected in upcoming years, Marconi notes.

Some patients enrolled in SELECT MDS-1 have already experienced promising results with the tamibarotene combination, including few toxicities like cytopenias, although these are patient and investigator opinions that may not reflect the overall study data, which are still immature, Marconi says. In general, however, clinicians feel comfortable using the tamibarotene regimen, Marconi concludes.