Lenalidomide is the standard of care for patients who are transfusion dependent with chromosome 5q deletion (del[5q]) myelodysplastic syndromes. In the SintraREV trial, we aimed to investigate whether an early intervention of low lenalidomide doses for 2 years could delay transfusion dependency in patients with anaemia who were not transfusion dependent. This randomised, double-blind, phase 3 trial, was conducted at 22 sites (University Hospitals) in Spain, France, and Germany. Eligible patients were aged 18 years or older diagnosed with low-risk or intermediate-1-risk del(5q) myelodysplastic syndromes with non-transfusion-dependent anaemia (according to the IPSS), were erythropoietin-stimulating agents naive, and had an ECOG performance status of 2 or less. Patients were randomly assigned (2:1) by means of a telephone system to receive lenalidomide 5 mg daily in 28-day cycles versus placebo for 2 years. The primary endpoint was time to transfusion dependency based on blinded independent central review. Analysis were by intent-to-treat (ITT) and evaluable population. Safety analyses included all participants who received at least one dose of treatment. This trial is registered with () and EudraCT (2009-013619-36) and is complete. Between Feb 15, 2010, and Feb 21, 2018, 61 patients were randomly assigned to receive lenalidomide (n=40; two did not receive treatment) or placebo (n=21). The median age was 72·2 (IQR 65·4–81·9) years, 50 (82%) patients were female, and 11 (18%) were male. The median follow-up time was 60·6 (IQR 32·1–73·9) months. Regarding primary endpoint, median time to transfusion dependency was not reached (95% CI not applicable) in the lenalidomide group versus 11·6 months (95% CI 0·00–30·11) in the placebo group (p=0·0027). Lenalidomide significantly reduced the risk of transfusion dependency by 69·8% (hazard ratio 0·302, 95% CI 0·132–0·692; p=0·0046). The most frequent treatment-related adverse event was neutropenia, occurring in 24 (63%) of 38 patients in the lenalidomide group (grade 3 and 4 in 17 [45%] patients and one [3%], respectively) and in four (19%) of 21 patients in the placebo group (grade 3 in one [5%] patient). Thrombocytopenia was detected in seven (18%) of 38 patients receiving lenalidomide (grade 3 in two [5%] patients). Regarding the non-haematological toxicity, skin disorders (rash nine [23%] of 38 patients) were the most frequently described toxicities among patients receiving lenalidomide, being grade 3 in one (3%) of 38 patients. 19 serious adverse events were reported in 13 patients, 18 in the lenalidomide group and one in the placebo group, five of which were potentially related to the study drug. No treatment-related deaths were identified. An early approach with low doses of lenalidomide across two years delays the time to transfusion dependency and improves the rate and quality of the responses, with a manageable safety profile in patients who are non-transfusion dependent with del(5q) low-risk myelodysplastic syndromes. Bristol Myers Squibb.

中文翻译：

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低剂量来那度胺与安慰剂治疗低风险 del(5q) 骨髓增生异常综合征的非输血依赖患者 (SintraREV)：一项随机、双盲 3 期试验


来那度胺是患有输血依赖性染色体 5q 缺失 (del[5q]) 骨髓增生异常综合征患者的标准治疗方法。在 SintraREV 试验中，我们旨在研究 2 年低来那度胺剂量的早期干预是否可以延迟非输血依赖性贫血患者的输血依赖性。这项随机、双盲、3 期试验在西班牙、法国和德国的 22 个地点（大学医院）进行。符合条件的患者年龄为 18 岁或以上，诊断患有低风险或中 1 风险 del(5q) 骨髓增生异常综合征并伴有非输血依赖性贫血（根据 IPSS），未接受过促红细胞生成素药物治疗，并且接受过 ECOG性能状态为 2 或更低。通过电话系统将患者随机分配（2:1），接受 28 天周期的每日 5 mg 来那度胺治疗，与安慰剂治疗 2 年。主要终点是基于盲法独立中央审查的输血依赖时间。按意向治疗 (ITT) 和可评估人群进行分析。安全性分析包括所有接受至少一剂治疗的参与者。该试验已在 () 和 EudraCT (2009-013619-36) 上注册并已完成。 2010年2月15日至2018年2月21日期间，61名患者被随机分配接受来那度胺（n=40；两人未接受治疗）或安慰剂（n=21）。中位年龄为 72·2 (IQR 65·4–81·9) 岁，50 名患者 (82%) 为女性，11 名患者 (18%) 为男性。中位随访时间为 60·6 (IQR 32·1–73·9) 个月。关于主要终点，来那度胺组未达到输血依赖的中位时间（95% CI 不适用），而安慰剂组为 11·6 个月（95% CI 0·00–30·11）（p=0·0027） ）。 来那度胺显着降低输血依赖风险 69·8%（风险比 0·302，95% CI 0·132–0·692；p=0·0046）。最常见的治疗相关不良事件是中性粒细胞减少症，来那度胺组的 38 名患者中有 24 名患者 (63%) 出现中性粒细胞减少症（分别为 17 名患者 [45%] 和 1 名患者 [3%]，发生 3 级和 4 级），4 名患者发生中性粒细胞减少症。安慰剂组 21 名患者中的 19%（1 名 [5%] 患者为 3 级）。 38 名接受来那度胺治疗的患者中，有 7 名 (18%) 检测到血小板减少症（两名 [5%] 患者为 3 级）。关于非血液学毒性，皮肤疾病（38 名患者中出现 9 次皮疹 [23%]）是接受来那度胺治疗的患者中最常描述的毒性，38 名患者中 1 名（3%）出现 3 级毒性。 13 名患者报告了 19 项严重不良事件，其中来那度胺组 18 名，安慰剂组 1 名，其中 5 名可能与研究药物相关。没有发现与治疗相关的死亡。两年内使用低剂量来那度胺的早期方法可延迟出现输血依赖的时间，并提高反应率和质量，对于患有 del(5q) 低危骨髓增生异常综合征的非输血依赖患者来说，安全性可控。百时美施贵宝。