The ENHANCE-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated AML unfit for intensive therapy.

The phase 3 ENHANCE-3 study aimed to determine whether magrolimab (magrolimab arm) was superior to placebo (control arm) when either was combined with venetoclax and azacitidine.

第三阶段ENHANCE-3研究旨在确定当与维奈克拉和阿糖胞苷联合使用时，magrolimab（magrolimab组）是否优于安慰剂（对照组）。

Adults with previously untreated AML who were ineligible for IC were randomized to receive magrolimab (1 mg/kg on days 1 and 4, 15 mg/kg on day 8, 30 mg/kg on days 11 and 15, then weekly for 5 weeks, and then every 2 weeks) or placebo, venetoclax (100 mg on day 1, 200 mg on day 2, and 400 mg daily thereafter), and azacitidine (75 mg/m2 days 1-7) in 28-day cycles.

先前未经治疗且不符合IC治疗条件的成人AML患者被随机分配接受magrolimab（第1天和第4天1 mg/kg，第8天15 mg/kg，第11天和第15天30 mg/kg，然后每周一次持续5周，之后每两周一次）或安慰剂，venetoclax（第1天100 mg，第2天200 mg，之后每天400 mg）以及azacitidine（第1-7天75 mg/m2）治疗，治疗周期为28天。

The primary end point was overall survival(OS); key secondary end points included complete remission (CR) rate and safety.

主要终点是总生存（OS）；关键次要终点包括完全缓解（CR）率和安全性。

After randomization of 378 patients, the trial was stopped at a prespecified interim analysis owing to futility.

在378名患者随机分组后，由于无效性，在预定的中期分析时停止了试验。

At final analysis, with median follow-up of 7.6 months (magrolimab arm) vs 7.4 months (control arm), median OS was 10.7 vs 14.1 months (hazard ratio, 1.178; 95% confidence interval, 0.848-1.637).

在最终分析中，中位随访时间为7.6个月（magrolimab组）对比7.4个月（对照组），中位总生存期为10.7个月对比14.1个月（风险比，1.178；95%置信区间，0.848-1.637）。

The CR rate within 6 cycles was 41.3% vs 46.0%.

6个周期内的完全缓解率分别为41.3%和46.0%。

Addition of magrolimab to venetoclax and azacitidine resulted in more fatal adverse events (19.0% vs 11.4%), primarily driven by grade 5 infections (11.1% vs 6.5%) and respiratory events (2.6% vs 0%).

将magrolimab添加到venetoclax和azacitidine中，导致了更多的致命不良事件（19.0%对比11.4%），主要由5级感染（11.1%对比6.5%）和呼吸系统事件（2.6%对比0%）引起。

There were similar incidences of any-grade infections, febrile neutropenia, and neutropenia between arms.

两组之间任何级别的感染、发热性中性粒细胞减少症和中性粒细胞减少症的发生率相似。

These results highlight the difficulty in improving outcomes for patients with AML who were ineligible for IC.

这些结果突显了改善不符合IC治疗的AML患者预后的困难。

This trial was registered at www.clinicaltrials.gov as #NCT05079230.

该试验已在www.clinicaltrials.gov上注册，注册号为#NCT05079230。