Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS.

Tamibarotene with azacitidine (AZA) showed complete remission (CR) rates in myeloid leukemia.

Tamibarotene与阿糖胞苷（AZA）联合使用在骨髓性白血病中显示出完全缓解（CR）率。

SELECT-MDS-1 was a phase 3 study comparing the activity of tamibarotene + AZA to placebo + AZA in these pts with newly diagnosed HR-MDS with RARA overexpression.

SELECT-MDS-1 是一项 III 期研究，比较了他莫昔芬加阿糖胞苷与安慰剂加阿糖胞苷在这些新诊断的高危骨髓增生异常综合征（HR-MDS）患者中的活性，这些患者具有 RARA 过表达。

Eligible pts had confirmed RARA overexpression, untreated MDS with higher-risk features by revised International Prognostic Scoring System (IPSS-R), and marrow blast count >5%.

符合条件的患者具有确认的 RARA 过表达，未经治疗的骨髓增生异常综合征，具有修订的国际预后评分系统（IPSS-R）定义的高危特征，并且骨髓原始细胞计数 >5%。

Pts were randomized 2:1 to receive tamibarotene + AZA or placebo + AZA, respectively.

患者按2:1的比例随机接受他米巴罗特 + AZA或安慰剂 + AZA治疗。

A total of 246 participants were randomized with 164 and 82 in the tamibarotene + AZA and placebo + AZA groups, respectively.

共有246名参与者被随机分配，其中164名接受他米巴罗特 + AZA治疗，82名接受安慰剂 + AZA治疗。

Baseline characteristics included: 69.9% male; median age 75 years (range, 38-93); primary MDS, 89.8%; MDS-excess blasts-1, 48% and MDS-excess blasts-2, 52%; and IPSS-R risk category intermediate (25.5%), high (35.7%), and very high (38.9%).

基线特征包括：男性占69.9%；中位年龄为75岁（范围，38-93岁）；原发性MDS占89.8%；MDS-异常增生-1占48%，MDS-异常增生-2占52%；以及IPSS-R风险类别为中等（25.5%）、高（35.7%）和非常高（38.9%）。

The study did not meet the primary end point of CR, with a P value of .2084 for the treatment effect in the tamibarotene + AZA group.

该研究未达到主要终点CR，对于他米巴罗特+AZA组的治疗效果，P值为.2084。

The CR rates were 23.81% and 18.75% in the tamibarotene + AZA and placebo + AZA groups, respectively.

在tamibarotene + AZA和placebo + AZA组中，完全缓解（CR）率分别为23.81%和18.75%。

The use of tamibarotene-based therapy to target RAR-α as a novel approach in pts with HR-MDS with RARA gene overexpression is not a paradigm, which can augment response rates beyond AZA monotherapy.

将tamibarotene为基础的治疗用于靶向RAR-α作为高危骨髓增生异常综合征（HR-MDS）患者中RARA基因过表达的一种新方法，并不是一个可以将缓解率提高超过AZA单药治疗的范例。

Further explorations of alternative approaches, including those with a biomarker, to alter the natural history of this disease are warranted.

进一步探索替代方法，包括那些具有生物标志物的方法，以改变这种疾病的自然病程是有必要的。

This trial was registered at www.clinicaltrials.gov as #NCT04797780.

这项试验已在www.clinicaltrials.gov上注册，注册号为#NCT04797780。