Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Hematol Oncol. 2021 Apr;39(2):215-221. doi: 10.1002/hon.2828. Epub 2020 Dec 10.
Rituximab, the first anti-CD20 monoclonal antibody, has dramatically improved outcomes for patients with B-cell lymphoproliferative disorders. Obinutuzumab was developed to potentiate activity and overcome resistance to rituximab. Clinical data suggest that obinutuzumab is superior to rituximab in follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Yet, it has increased toxicity. This systematic review and meta-analysis compiled all randomized controlled trials (RCTs) comparing obinutuzumab-based regimens with rituximab-based regimens to better assess their toxicity profile. Primary outcome was grade 3-4 infections; secondary outcomes included any adverse events (AE), grade 3-4 AE, drug discontinuation rate, and 3-years mortality. Relative risks (RRs) were estimated and pooled using a fixed-effect model, unless there was significant heterogeneity, in which case a random-effects model was used. Our comprehensive search yielded five RCTs conducted between 2009 and 2014, including 4247 patients. The trials included FL patients, CLL and diffuse large B cell lymphoma. Monoclonal antibodies were given with different chemotherapy regimens (in four trials) or as monotherapy (in one trial). The point estimate favored increase in both grade 3-4 infections rate (RR 1.17 [95% CI, 1.0-1.36]) and any AE rate (RR 1.05 [95% 1-1.1]) with obinutuzumab, although this was not statistically significant. There was a significantly increased rate of grade 3-4 AE (RR 1.15 [95% CI, 1.09-1.2]), as well as grade 3-4 toxicities including thrombocytopenia (RR 2.8 [95% CI, 1.92-4.06]), infusion related reactions (RR 2.8 [95% CI, 2.16-3.64]) and cardiac events (RR 1.65 [95% CI, 1.11-2.46]). There was no significant difference in grade 3-4 anemia and neutropenia nor in the 3-year mortality rate. The point estimate favored increase in discontinuation rate due to AE with obinutuzumab, although without statistical significance (RR 1.24 [95% CI, 1.0-1.54]). In conclusion, physicians need to weigh the clinical benefits of this agent against higher toxicity.
奥滨尤妥珠单抗是一种针对 CD20 的单克隆抗体，旨在增强活性并克服对利妥昔单抗的耐药性。临床数据表明，奥滨尤妥珠单抗在滤泡性淋巴瘤（FL）和慢性淋巴细胞白血病（CLL）中的疗效优于利妥昔单抗。然而，它的毒性也更高。本系统评价和荟萃分析综合了所有比较奥滨尤妥珠单抗方案与利妥昔单抗方案的随机对照试验（RCT），以更好地评估其毒性特征。主要结局为 3-4 级感染；次要结局包括任何不良事件（AE）、3-4 级 AE、停药率和 3 年死亡率。采用固定效应模型估计和汇总相对风险（RR），除非存在显著异质性，否则采用随机效应模型。我们的全面检索产生了五项 2009 年至 2014 年期间进行的 RCT，共纳入 4247 例患者。这些试验包括 FL 患者、CLL 和弥漫性大 B 细胞淋巴瘤患者。单克隆抗体与不同的化疗方案联合使用（在四项试验中）或单独使用（在一项试验中）。奥滨尤妥珠单抗治疗组的 3-4 级感染率（RR 1.17 [95%CI，1.0-1.36]）和任何 AE 率（RR 1.05 [95%CI，1.0-1.1]）的点估计值均升高，尽管这并不具有统计学意义。奥滨尤妥珠单抗治疗组 3-4 级 AE 发生率（RR 1.15 [95%CI，1.09-1.2]）、3-4 级毒性发生率（包括血小板减少症[RR 2.8 [95%CI，1.92-4.06]）、输注相关反应（RR 2.8 [95%CI，2.16-3.64]）和心脏事件（RR 1.65 [95%CI，1.11-2.46]）的发生率均显著升高。3-4 级贫血和中性粒细胞减少症的发生率以及 3 年死亡率无显著差异。奥滨尤妥珠单抗治疗组因 AE 而停药率的点估计值升高，但无统计学意义（RR 1.24 [95%CI，1.0-1.54]）。综上所述，医生需要权衡该药物的临床获益与更高的毒性。
