Background The Chronic Lymphocytic Leukemia (CLL) treatment strategies have transitioned from chemotherapy and chemoimmunotherapy to chemo-free regimens. Frequentist network meta-analysis allows for both direct and indirect comparisons between different treatments. Methods Randomized controlled trials assessing first-line treatments were included. Outcomes were progression-free survival (PFS), overall survival, undetectable minimal residual disease (MRD), objective response rate, and adverse events. Studies with comparable characteristics also underwent subgroup analysis, stratifying by age, comorbidities, IGHV status, and cytogenetic abnormalities. Results 30 eligible trials involved 12,818 patients and 30 treatments were included. Acalabrutinib demonstrated a PFS advantage over ibrutinib and obinutuzumab-venetoclax (OV) in patients over 65 years old or with unmutated IGHV. In younger patients with comorbidities, Acalabrutinib-Obinutuzumab (AO) had superior PFS compared to Ibrutinib-Obinutuzumab (IO), Ibrutinib-Venetoclax (IV), and OV. For older patients with comorbidities, Acalabrutinib and AO both outperformed OV without significant difference between them. MRD-guided IV surpassed OV in patients without comorbidities. IO exhibited extended PFS benefits compared to OV in patients with mutated IGHV or with del(17p) and/or TP53 mutations. IV and IO have lower neutropenia rates than OV. IV have fewer infections than Acalabrutinib and AO. AO causes less diarrhea than IV but more headaches than IO and OV. OV has lower hypertension rates than IO. IV has fewer arthralgia than AO. For any grade secondary primary neoplasms, IV and OV is less than AO. Conclusion Tailored chemo-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different response spectra.

中文翻译：

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比较慢性淋巴细胞白血病一线治疗的疗效和安全性：一项网络荟萃分析


背景 慢性淋巴细胞白血病 （CLL） 治疗策略已从化疗和化学免疫疗法过渡到无化疗方案。Frequentist network meta 分析允许对不同治疗进行直接和间接比较。方法 纳入评估一线治疗的随机对照试验。结局是无进展生存期 （PFS） 、总生存期、检测不到的微小残留病 （MRD） 、客观缓解率和不良事件。具有相似特征的研究也进行了亚组分析，按年龄、合并症、IGHV 状态和细胞遗传学异常进行分层。结果 30 项符合条件的试验涉及 12,818 名患者，纳入 30 种治疗方法。在 65 岁以上或未突变的 IGHV 患者中，Acalabrutinib 的 PFS 优于 ibrutinib 和 obinutuzumab-venetoclax （OV）。在有合并症的年轻患者中，Acalabrutinib-Obinutuzumab （AO） 的 PFS 优于 Ibrutinib-Obinutuzumab （IO） 、Ibrutinib-Venetoclax （IV） 和 OV。对于有合并症的老年患者，Acalabrutinib 和 AO 均优于 OV，两者之间无显著差异。在无合并症的患者中，MRD 指导的 IV 超过 OV。与 OV 相比，IO 在 IGHV 突变或 del（17p） 和/或 TP53 突变患者中表现出更广泛的 PFS 益处。IV 和 IO 的中性粒细胞减少率低于 OV。IV 的感染比 Acalabrutinib 和 AO 少。AO 引起的腹泻比 IV 少，但比 IO 和 OV 引起的头痛更多。OV 的高血压发生率低于 IO。IV 的关节痛比 AO 少。对于任何级别的继发性原发性肿瘤，IV 和 OV 都小于 AO。 结论 可根据年龄、合并症、IGHV 状态和细胞遗传学异常选择量身定制的无化疗方案，以优化治疗结果，同时考虑不同的反应谱。