利妥昔单抗联合氟达拉滨和环磷酰胺(RFC)是治疗未经治疗的慢性淋巴细胞白血病(CLL)患者的标准治疗方法;然而,由于其毒性特征,其在“不适合”(共病和/或全剂量F-不合格)患者中的使用受到限制.我们进行了系统评价和贝叶斯网络荟萃分析(NMA),以确定市售干预措施对不适合CLL患者的一线治疗的相对疗效。
要纳入NMA,研究必须通过常见的治疗比较器联系起来,报告无进展生存期(PFS),和/或总生存率(OS),并至少满足五个纳入标准之一:中位累积疾病评分>6,中位肌酐清除率≤70mL/min,现有的合并症,中位年龄≥70岁,比较臂中没有全剂量F。手动审查,由外部专家验证,在所有符合这些标准中至少一项的研究中,还进行了这些研究,以确认他们评估了CLL不适合患者的一线治疗方案.
在不适合的患者中,主要的NMA(5项PFS研究和4项OS研究)在PFS方面明显偏好奥比单抗+苯丁酸氮芥(G-Clb)与利妥昔单抗+苯丁酸氮芥(R-Clb),Ofatumumab+苯丁酸氮芥(O-Clb),氟达拉滨和苯丁酸氮芥(危险比中位数[HR]分别为0.43、0.33、0.20和0.19),与利妥昔单抗+苯达莫司汀(R-Benda)和RFC-Lite相比,疗效有更好的趋势(HR中位数分别为0.81和0.88)。OS结果与PFS数据基本一致,(中位数HR分别为0.48、0.53和0.81)对于G-Clb与Clb,O-Clb,R-Clb0.35和0.81与F和R-Benda,分别);然而,OS结果与较高的不确定度相关.治疗排名反映了与其他治疗策略相比,G-Clb改善的PFS和OS(两个终点的中位数排名为1)。
对于不适合治疗的初治CLL患者,G-Clb可能比我们的NMA中选择的其他治疗方案表现出更好的疗效。
F.霍夫曼-拉罗氏有限公司.
Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in \'unfit\' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic
review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients.
For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A manual
review, validated by external experts, of all studies that met at least one of these criteria was also performed to confirm that they evaluated first-line therapeutic options for unfit patients with CLL.
In unfit patients, the main NMA (five studies for PFS and four for OS) demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil (G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil (O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33, 0.20, and 0.19, respectively), and a trend for better efficacy versus rituximab +
bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88, respectively). OS results were generally consistent with PFS data, (median HR 0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35 and 0.81 versus F and R-Benda, respectively); however, the OS findings were associated with higher uncertainty. Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies (median rank of one for both endpoints).
G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL.
F. Hoffmann-La Roche Ltd.