Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions
Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions
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DOI：
10.1056/nejmoa1313984
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发表时间：
2014-03-20
影响因子：
158.5
通讯作者：
Hallek, Michael
中科院分区：
文献类型：
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作者：
Goede, Valentin;Fischer, Kirsten;Hallek, Michael
背景抗CD 20单克隆抗体利妥昔单抗联合化疗药物已被证明可延长健康的慢性淋巴细胞白血病（CLL）患者的总生存期，但对共存疾病的患者无效。我们研究了2型糖工程抗体obinutuzumab（也被称为GA 101）相比，利妥昔单抗，每一个与苯丁酸氮芥相结合，在以前未经治疗的慢性淋巴细胞白血病和共存conditions.MethodsWe随机分配781例患者以前未经治疗的慢性淋巴细胞白血病和得分高于6的累积疾病评定量表（CIRS）（范围，0至56，评分越高表示健康状况越差）或估计的肌酐清除率为30至69 ml/min，以接受苯丁酸氮芥、obinutuzumab加苯丁酸氮芥或利妥昔单抗加苯丁酸氮芥。主要终点是评估者评估的无进展survival.ResultsThe患者的中位年龄为73岁，肌酐清除率为62毫升每分钟，CIRS评分为8在基线。与苯丁酸氮芥单药治疗相比，奥尤珠单抗-苯丁酸氮芥或利妥昔单抗-苯丁酸氮芥治疗可提高缓解率并延长无进展生存期（奥尤珠单抗-苯丁酸氮芥组的中位无进展生存期为26.7个月，苯丁酸氮芥单药组为11.1个月;进展或死亡的风险比为0.18; 95%置信区间[CI]为0.13 - 0.24; P
BackgroundThe monoclonal anti-CD20 antibody rituximab, combined with chemotherapeutic agents, has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia (CLL) but not in those with coexisting conditions. We investigated the benefit of the type 2, glycoengineered antibody obinutuzumab (also known as GA101) as compared with that of rituximab, each combined with chlorambucil, in patients with previously untreated CLL and coexisting conditions.MethodsWe randomly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil. The primary end point was investigator-assessed progression-free survival.ResultsThe patients had a median age of 73 years, creatinine clearance of 62 ml per minute, and CIRS score of 8 at baseline. Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil, as compared with chlorambucil monotherapy, increased response rates and prolonged progression-free survival (median progression-free survival, 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone; hazard ratio for progression or death, 0.18; 95% confidence interval [CI], 0.13 to 0.24; P