Department of Hematology-Oncology, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.
Biostatistics Unit, IRCCS Regina Elena, Rome, Italy.
Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):216-223. doi: 10.1016/j.clml.2020.10.012. Epub 2020 Oct 29.
Available targeted agents (TAs) for the upfront therapy of chronic lymphocytic leukemia (ie, ibrutinib, acalabrutinib, venetoclax) have rarely been compared in head-to-head clinical trials. In search of data for evidence-based treatment decisions, a systematic literature review and network meta-analysis was performed.
The screening process adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA).
Only 3 trials were suitable for the base-case network analysis (ILLUMINATE, ELEVATE-TN, and CLL14). Regarding progression-free survival (PFS), fixed-effect analyses comparing ibrutinib-obinutuzumab (IO) with venetoclax-obinutuzumab (VO) (relative risk [RR], 1.52; 95% confidence interval [CI], 0.82-2.81), acalabrutinib (A) with IO (RR, 0.87; 95% CI, 0.47-1.61), and A with VO (RR, 0.57; 95% CI, 0.32-1.01) revealed that the upper limit of the 95% CI for RR did exceed the 1.0 value. This indicates a lack of significant difference in PFS for IO, VO, and A. In contrast, acalabrutinib plus obinutuzumab (AO) improved PFS in comparison with IO (RR, 0.43; 95% CI, 0.22-0.87) and VO (RR, 0.29; 95% CI, 0.15-0.56). No differences in the frequency of adverse events was observed across different TAs. Also, the analysis of PFS in relationship with high-risk genetic features (ie, TP53 aberrations, IGHV unmutated, 11q deletion) showed similar results for different TAs. However, patients with unmutated IGHV status fared better with AO than with VO in terms of PFS.
This systematic review and network meta-analysis indicated that upfront AO prolongs PFS in comparison with IO and VO, whereas no differences are observed between IO, VO, and single-agent A. Hopefully, ongoing studies will further delineate the position of different TAs in chronic lymphocytic leukemia therapy based on effectiveness, availability, safety, cost, and treatment objectives.
目前针对慢性淋巴细胞白血病（即伊布替尼、阿卡替尼、维奈托克）的一线治疗药物（TAs）很少在头对头临床试验中进行比较。为了寻找循证治疗决策的数据，我们进行了系统的文献回顾和网络荟萃分析。
筛选过程符合系统评价和荟萃分析的首选报告项目（PRISMA）的指导原则。
仅有 3 项试验适合进行基本网络分析（ILLUMINATE、ELEVATE-TN 和 CLL14）。关于无进展生存期（PFS），固定效应分析比较伊布替尼-奥滨尤妥珠单抗（IO）与维奈托克-奥滨尤妥珠单抗（VO）（风险比[RR]，1.52；95%置信区间[CI]，0.82-2.81）、阿卡替尼（A）与 IO（RR，0.87；95% CI，0.47-1.61）和 A 与 VO（RR，0.57；95% CI，0.32-1.01）的 RR 上限均未超过 1.0，这表明 IO、VO 和 A 的 PFS 之间无显著差异。相比之下，阿卡替尼联合奥滨尤妥珠单抗（AO）可改善 PFS 与 IO（RR，0.43；95% CI，0.22-0.87）和 VO（RR，0.29；95% CI，0.15-0.56）相比。不同 TAs 的不良反应频率无差异。此外，不同 TAs 的 PFS 与高危遗传特征（即 TP53 异常、IGHV 未突变、11q 缺失）之间的分析也得到了类似的结果。然而，与 VO 相比，IGHV 未突变的患者使用 AO 的 PFS 获益更好。
本系统评价和网络荟萃分析表明，与 IO 和 VO 相比，一线使用 AO 可延长 PFS，而 IO、VO 和单药 A 之间无差异。希望正在进行的研究将根据有效性、可及性、安全性、成本和治疗目标进一步确定不同 TAs 在慢性淋巴细胞白血病治疗中的地位。
