Giagounidis Aristoteles, Mufti Ghulam J, Mittelman Moshe, Sanz Guillermo, Platzbecker Uwe, Muus Petra, Selleslag Dominik, Beyne-Rauzy Odile, te Boekhorst Peter, del Cañizo Consuelo, Guerci-Bresler Agnès, Nilsson Lars, Lübbert Michael, Quesnel Bruno, Ganser Arnold, Bowen David, Schlegelberger Brigitte, Göhring Gudrun, Fu Tommy, Benettaib Bouchra, Hellström-Lindberg Eva, Fenaux Pierre
Marien Hospital Düsseldorf, Düsseldorf, Germany.
Eur J Haematol. 2014 Nov;93(5):429-38. doi: 10.1111/ejh.12380. Epub 2014 Jun 9.
A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q).
Patients received lenalidomide 10 mg/d (days 1-21; n = 47) or 5 mg/d (days 1-28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively.
Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3-4 adverse event was myelosuppression.
These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q).
对随机3期MDS - 004研究进行亚组分析，以评估国际预后评分系统（IPSS）定义的低危/中危-1（Int-1）风险且伴有孤立性5号染色体长臂缺失（del(5q)）的骨髓增生异常综合征（MDS）患者的预后。
患者接受来那度胺10mg/d（第1 - 21天；n = 47）或5mg/d（第1 - 28天；n = 43），每28天为一个周期，或接受安慰剂治疗（n = 45）。在安慰剂组和来那度胺5mg组中，分别有84%和58%的患者在16周时交叉接受来那度胺5mg或10mg治疗。
来那度胺10mg组（57.4%；P < 0.0001）和5mg组（37.2%；P = 0.0001）的红细胞输注独立（RBC - TI）≥182天的发生率高于安慰剂组（2.2%）。细胞遗传学缓解率（主要 + 次要缓解）分别为56.8%（P < 0.0001）、23.1%（P = 0.0299）和0%。来那度胺10mg组、5mg组和安慰剂组急性髓系白血病进展的两年累积风险分别为12.6%、17.4%和16.7%。在一项6个月的标志性分析中，RBC - TI≥182天的来那度胺治疗患者的总生存期长于无反应者（P = 0.0072）。最常见的3 - 4级不良事件是骨髓抑制。
这些数据支持来那度胺在IPSS定义的低危/中危-1风险且伴有孤立性del(5q)的输血依赖型MDS患者中的临床益处和可接受的安全性。
