Selinexor Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Myelofibrosis: Phase III SENTRY Trial.

Selinexor, an oral inhibitor of exportin 1, has demonstrated activity in MF.

Selinexor，一种口服的exportin 1抑制剂，在MF中显示出活性。

We evaluated selinexor plus ruxolitinib versus ruxolitinib alone in Janus kinase inhibitor-naïve MF.

我们在Janus激酶抑制剂未经治疗的MF患者中评估了selinexor联合ruxolitinib与单独使用ruxolitinib的疗效。

Methods

In this double-blind, phase III trial, patients were randomly assigned (2:1) to receive selinexor plus ruxolitinib or placebo plus ruxolitinib.

在这项双盲、III期试验中，患者被随机分配（2:1）接受selinexor联合ruxolitinib或安慰剂联合ruxolitinib。

Coprimary end points were spleen volume reduction ≥35% (SVR35) and absolute mean change in total symptom score (AbsTSS; excluding fatigue) from baseline to week 24.

主要终点是脾脏体积减少≥35%（SVR35）和从基线到第24周的总症状评分（AbsTSS；不包括疲劳）的绝对平均变化。

Results

A total of 353 patients were randomly assigned.

共有353名患者被随机分配。

At week 24, SVR35 was achieved in 49.8% of the selinexor plus ruxolitinib group versus 28.0% of the placebo plus ruxolitinib group (difference, 21.8 percentage points; odds ratio, 2.58 [95% CI, 1.60 to 4.17]; P < .0001).

在第24周，selinexor联合ruxolitinib组的SVR35达到49.8%，而安慰剂联合ruxolitinib组为28.0%（差异，21.8个百分点；比值比，2.58 [95% CI, 1.60至4.17]；P < .0001）。

Differences were evident by week 12 and through week 36.

差异在第12周就很明显，并持续到第36周。

The AbsTSS coprimary end point was not met; however, symptom scores improved from baseline in both groups (-9.9 selinexor plus ruxolitinib, -10.9 placebo plus ruxolitinib), with no significant between-group difference.

尽管未达到AbsTSS共同主要终点，但两组的症状评分从基线开始都有所改善（selinexor加ruxolitinib组为-9.9，安慰剂加ruxolitinib组为-10.9），两组之间没有显著差异。

At a median follow-up of approximately 12 months, the overall survival(OS) hazard ratiowas 0.43 ([95% CI, 0.19 to 1.00]; nominal P = .022).

在大约12个月的中位随访期，总体生存（OS）风险比为0.43（[95% CI, 0.19至1.00]；名义P = .022）。

Grade ≥3 adverse events (AEs) occurred in 70.1% and 50.0% of patients in the selinexor plus ruxolitinib or placebo plus ruxolitinib groups, respectively, most commonly anemia, thrombocytopenia, and neutropenia.

在selinexor加ruxolitinib组或安慰剂加ruxolitinib组的患者中，分别有70.1%和50.0%发生了3级或更高级别的不良事件（AEs），最常见的为贫血、血小板减少症和中性粒细胞减少症。

Nausea was more frequent with selinexor but predominantly low-grade and early.

使用selinexor的患者恶心发生更频繁，但主要是低级别的，并且出现在早期。

Conclusions

In patients with JAK inhibitor-naïve MF, selinexor plus ruxolitinib met its coprimary end point of improved SVR35 but did not meet the AbsTSS coprimary end point, compared with placebo plus ruxolitinib.

在未经JAK抑制剂治疗的骨髓纤维化患者中，selinexor加ruxolitinib达到了改善SVR35的共同主要终点，但未达到AbsTSS共同主要终点，与安慰剂加ruxolitinib相比。

An early OS difference was observed.

观察到早期总体生存率的差异。

The safety profile was consistent with known AE profiles of the individual agents.

安全性特征与已知的各个药物的不良事件特征一致。