US Food and Drug Administration Approval Summary: Imetelstat for Selected Patients With Low- to Intermediate-1 Risk Myelodysplastic Syndromes With Transfusion-Dependent Anemia.

The approval was based on a randomized (2:1), double-blind, placebo-controlledmulticenter trial, Study MDS3001.

该批准基于一项随机（2:1）、双盲、安慰剂对照的多中心试验，即MDS3001研究。

In the protocol-specified primary analysis, the ≥8-week RBC transfusion independence (RBC-TI) rate was 39.8% (95% CI, 30.9 to 49.3) in the imetelstat group versus 15% (95% CI, 7.1 to 26.6) in the placebo group (P < .001).

在协议规定的首要分析中，接受imetelstat治疗的组别中≥8周红细胞输注独立（RBC-TI）的比率是39.8%（95%置信区间，30.9至49.3），而接受安慰剂治疗的组别是15%（95%置信区间，7.1至26.6）（P < .001）。

This was supported by the rate of ≥24-week RBC-TI of 28% (95% CI, 20.1 to 37) in the imetelstat group versus 3.3% (95% CI, 0.4 to 11.5) in the placebo group (P < .001).

这一结果得到了≥24周RBC-TI比率的支持，其中imetelstat组为28%（95%置信区间，20.1至37），而安慰剂组为3.3%（95%置信区间，0.4至11.5）（P < .001）。

However, there was no major difference between arms regarding the key secondary end point of erythroid response (HI-E) per International Working Group 2006 criteria or secondary end points reflective of a disease-modifying effect such as complete remission rate and overall survival. The most common adverse reactions were thrombocytopenia, leukopenia, neutropenia, increased liver enzymes, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19, and headache.

然而，在按照2006年国际工作组标准评估的红细胞反应（HI-E）这一关键次要终点，或反映疾病修饰效应的次要终点，如完全缓解率和总生存方面，两组之间没有显著差异。最常见的不良反应包括血小板减少症、白细胞减少症、中性粒细胞减少症、肝酶升高、疲劳、部分凝血活酶时间延长、关节痛/肌痛、COVID-19和头痛。

The rate of grade 3 to 4 neutropenia and thrombocytopenia were 72% and 65%, respectively, in the imetelstat arm compared with 7% and 8% in the placebo arm.

在imetelstat组中，3至4级中性粒细胞减少症和血小板减少症的发生率分别为72%和65%，而在安慰剂组中分别为7%和8%。

Despite the high incidenceof neutropenia and thrombocytopenia, the FDA determined that the benefits outweighed the risks in this patient population with high unmet need.

尽管中性粒细胞减少症和血小板减少症的发生率很高，但FDA认为在这一高未满足需求的患者群体中，益处超过了风险。

Postmarketing requirements were issued to evaluate long-term safety and to conduct a randomized trial comparing at least two dosages of imetelstat to potentially minimize risks of imetelstat treatment and improve tolerability.

发布了上市后要求，以评估长期安全性，并进行至少两种剂量的imetelstat的随机试验，以尽量减少imetelstat治疗的风险并提高其耐受性。