Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions
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DOI：
10.1056/nejmoa1815281
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发表时间：
2019-06-06
影响因子：
158.5
通讯作者：
Hallek, M.
中科院分区：
文献类型：
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作者：
Fischer, K.;Al-Sawaf, O.;Hallek, M.
BCL 2抑制剂venetoclax已在慢性淋巴细胞白血病（CLL）患者中显示出活性，但其与其他药物联合治疗CLL和共存疾病患者的疗效尚不清楚。方法在这项开放标签的3期试验中，我们研究了维奈托克和obinutuzumab在既往未经治疗的CLL和并存疾病患者中的固定持续时间治疗。累积疾病评定量表评分大于6（评分范围为0 - 56，评分越高表明器官系统功能受损越严重）或计算的肌酐清除率小于70 ml/min的患者随机分配接受维奈托克-奥比妥珠单抗或苯丁酸氮芥-奥比妥珠单抗治疗。主要终点是评估者评估的无进展生存期。还评价了每种方案的安全性。结果共有432例患者（中位年龄72岁，中位累积疾病评定量表评分8分，中位肌酐清除率66.4 ml/min）接受随机分组，每组216例。在中位随访28.1个月后，维奈托克-奥比妥珠单抗组发生了30起主要终点事件（疾病进展或死亡），苯丁酸氮芥-奥比妥珠单抗组发生了77起（风险比，0.35; 95%置信区间[CI]，0.23至0.53; P
Background The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known. Methods In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated. Results In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P