Rioufol Catherine, Salles Gilles
Hospices Civils de Lyon, Unité de Pharmacie Clinique Oncologique, Université de Lyon - EMR 3738, Pierre-Bénite, France.
Expert Rev Hematol. 2014 Oct;7(5):533-43. doi: 10.1586/17474086.2014.953478. Epub 2014 Aug 28.
Chronic lymphocytic leukemia (CLL) is a frequent hematological malignancy that is incurable using standard approaches. Two anti-CD20 monoclonal antibodies (mAb), rituximab and ofatumumab, have been approved for CLL treatment. A new glycoengineered type II humanized anti-CD20 mAb, obinutuzumab (GA101), has been developed and demonstrates increased activity against B-cell malignancies by inducing direct cell death and better antibody-dependent cellular cytotoxicity. In a recent randomized Phase III study in patients with newly diagnosed CLL and coexisting conditions, obinutuzumab plus chlorambucil demonstrated significant improvement in progression-free survival and several other outcome parameters, in contrast to rituximab plus chlorambucil. Grade 3-4 infusion-related reactions and neutropenia occurred more frequently in patients who received obinutuzumab compared with those who received rituximab; however, the rate of serious infections was similar. Obinutuzumab represents a promising new option for patients with CLL and must be investigated with other chemotherapy regimens or with new targeted agents.
慢性淋巴细胞白血病(CLL)是一种常见的血液系统恶性肿瘤,采用标准方法无法治愈。两种抗CD20单克隆抗体(mAb),利妥昔单抗和奥法木单抗,已被批准用于CLL治疗。一种新型糖基工程化II型人源化抗CD20 mAb,奥妥珠单抗(GA101)已被研发出来,并通过诱导直接细胞死亡和更好的抗体依赖性细胞毒性,显示出对B细胞恶性肿瘤增强的活性。在最近一项针对新诊断的CLL患者及共存病症的随机III期研究中,与利妥昔单抗加苯丁酸氮芥相比,奥妥珠单抗加苯丁酸氮芥在无进展生存期和其他几个结局参数方面显示出显著改善。与接受利妥昔单抗的患者相比,接受奥妥珠单抗的患者中3-4级输注相关反应和中性粒细胞减少症的发生频率更高;然而,严重感染的发生率相似。奥妥珠单抗是CLL患者一种有前景的新选择,必须与其他化疗方案或新的靶向药物联合进行研究。