Valeria Santini, University of Florence, Florence, Italy; Antonio Almeida, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal; Aristoteles Giagounidis and Stefanie Gröpper, Marien Hospital Düsseldorf; Norbert Gattermann, Heinrich-Heine-Universität, Düsseldorf; Uwe Platzbecker, Technical University Dresden, Dresden, Germany; Anna Jonasova, Charles University General Hospital, Prague, Czech Republic; Norbert Vey, Centre Régional de Lutte Contre le Cancer, Marseille; Pierre Fenaux, Université Paris, Paris, France; Francis Séguy and Albert Hoenekopp, Celgene International, Boudry, Switzerland; Ghulam J. Mufti, King's College Hospital, London, United Kingdom; Rena Buckstein, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Moshe Mittelman and Ron Ram, Tel Aviv University; Ofer Shpilberg, Assuta Medical Center, Tel Aviv, Israel; Consuelo del Cañizo, Hospital Universitario de Salamanca, Salamanca; Alberto Risueño, Celgene Institute for Translational Research Europe, Seville, Spain; Keiya Ozawa, The University of Tokyo, Tokyo, Japan; Kyle J. MacBeth, Celgene Corporation, San Francisco, CA; and Jianhua Zhong and C.L. Beach, Celgene Corporation, Summit, NJ.
J Clin Oncol. 2016 Sep 1;34(25):2988-96. doi: 10.1200/JCO.2015.66.0118. Epub 2016 Jun 27.
This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion-dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents.
In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety.
RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia.
Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide.
本项国际 III 期、随机、安慰剂对照、双盲研究评估了来那度胺在不适合或对红细胞生成刺激剂耐药的低危非 del(5q)骨髓增生异常综合征且依赖红细胞输血的患者中的疗效和安全性。
共 239 例患者被随机分配（2:1）接受来那度胺（n=160）或安慰剂（n=79）治疗，每天一次（28 天周期）。主要终点是红细胞输血独立性（TI）≥8 周的发生率。次要终点是红细胞 TI≥24 周、红细胞 TI 持续时间、红细胞反应、健康相关生活质量（HRQoL）和安全性。
来那度胺组和安慰剂组分别有 26.9%和 2.5%的患者达到红细胞 TI≥8 周（P<0.001）。接受治疗 16 周内达到红细胞 TI 的患者中，90%的患者有反应。来那度胺组的红细胞 TI 中位持续时间为 30.9 周（95%CI，20.7 至 59.1）。基于 112 天评估，来那度胺组中 4 单位以上的红细胞输注减少率为 21.8%，安慰剂组为 0%。在基线时内源性促红细胞生成素水平较低（≤500 mU/mL）的患者中观察到更高的反应率（>500 mU/mL 的为 34.0%，而<500 mU/mL 的为 15.5%）。在第 12 周时，两组间 HRQoL 评分自基线的平均变化无显著差异，表明来那度胺未对 HRQoL 产生不利影响。达到红细胞 TI≥8 周与 HRQoL 的显著改善相关（P<0.01）。最常见的治疗相关不良事件是中性粒细胞减少和血小板减少。
来那度胺可使不适合或对红细胞生成刺激剂耐药的低危非 del(5q)骨髓增生异常综合征且依赖红细胞输血的患者中 26.9%的患者持续获得红细胞 TI。来那度胺的应答与 HRQoL 的改善相关。治疗相关不良事件数据与来那度胺已知的安全性特征一致。
