TOPLINE:

In a phase 3 trial of 246 patients with higher-risk myelodysplastic syndrome (MDS) and retinoic acid receptor alpha (RARA) gene overexpression, tamibarotene plus azacitidine did not significantly improve complete remission rates compared to placebo plus azacitidine. The complete remission rates were 23.81% vs 18.75% (P = .2084), though higher transfusion independence was achieved in the combination arm.

METHODOLOGY:

• A total of 246 participants with newly diagnosed higher-risk MDS and RARA gene overexpression were randomized 2:1 to receive tamibarotene plus azacitidine (n = 164) or placebo plus azacitidine (n = 82).
• Participants received oral tamibarotene 6 mg twice daily or placebo on days 8-28 of each 28-day cycle, with all receiving azacitidine 75 mg/m² on days 1-7 or days 1-5, 8, and 9.
• Baseline characteristics included 69.9% male patients; median age, 75 years (range, 38-93); primary MDS in 89.8%; and revised International Prognostic Scoring System risk categories of intermediate (25.5%), high (35.7%), and very high (38.9%).
• The study was conducted at 135 sites across 13 countries with complete remission rate by cycle 7, day 1 as the primary endpoint.

TAKEAWAY:

• The complete remission rates were 23.81% (95% CI, 16.7%-32.2%) in the tamibarotene plus azacitidine group vs 18.75% (95% CI, 10.1%-30.5%) in the placebo plus azacitidine group (P = .2084).
• Median time to complete remission was longer in the tamibarotene arm (4.8 months) than in the placebo arm (3.6 months), while the median duration of complete remission was 15.7 months (95% CI, 6.9 to not estimable) vs not estimable (95% CI, 16.6 to not estimable).
• A higher proportion of participants in the tamibarotene plus azacitidine group achieved transfusion independence than in the placebo plus azacitidine group, with 79.55% vs 57.14% of transfusion-dependent patients at baseline becoming independent.
• The very high-risk group showed higher complete remission rates with tamibarotene plus azacitidine at 25% (95% CI, 14%-38.9%) than with placebo plus azacitidine at 3.7% (95% CI, 0.1%-19%).

IN PRACTICE:

“The success of the SELECT-MDS-1 trial was as an efficiently accrued international phase 3 trial that was biomarker driven, the first of its kind in MDS. Although the doublet combination tested in SELECT-MDS-1 with tamibarotene failed to meet the primary endpoint, it is noteworthy in a trial conducted at so many sites, to demonstrate an azacitidine monotherapy CR [complete remission] rate similar to that of modern azacitidine control arms,” the authors of the study wrote.

SOURCE:

This study was led by Amy DeZern, MD, Johns Hopkins University, Baltimore. It was published online in Blood Advances.

LIMITATIONS:

According to the authors, the lack of central pathology review and overall survival analysis data limited the understanding of clinical benefits. The discontinuation rate due to adverse events was more than twice as high in the tamibarotene arm than in the control arm, potentially limiting the ability of patients to achieve complete remission and proceed to transplant. Additionally, investigators may have developed bias in treatment assignment due to observable side effects like hypertriglyceridemia or skin changes, possibly leading to early discontinuation before response could be achieved.

DISCLOSURES:

This study was supported by Syros Pharmaceuticals Inc. Amy DeZern, MD, disclosed having relationships with AbbVie, Agios, Bristol Myers Squibb, Novartis, Kura, Geron, Servier, Keros, and Shattuck Labs. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.