本系统文献综述(CRD42023393903)和贝叶斯网络荟萃分析(NMA)旨在评估一线靶向治疗的相对安全性(acalabrutinib,伊布替尼,奥比努珠单抗,Ofatumumab,pirtobrutinib,ublituximab,umbralisib,维尼托克,zanubrutinib)用于高龄和/或合并症的慢性淋巴细胞白血病(CLL)患者。NMA显示,就总体安全性而言,扎努布替尼是最安全的治疗选择(例如,严重不良事件[AEs]1-5级),其次是维奈托克-奥比努珠单抗,在1-5级不良事件方面表现出优势。布鲁顿酪氨酸激酶抑制剂(BTKi)单药治疗在血液学不良事件发生风险方面更为有利,但是化学免疫疗法在心血管方面显示出优势,胃肠,和感染性AE。继发性癌症的风险在治疗之间相似。总之,靶向治疗与可变的和临床相关的AE相关。在具有高龄和/或合并症的初治CLL患者中,当用作单一疗法而不是与免疫剂组合时,该疗法似乎更安全。
This systematic literature
review (CRD42023393903) and a Bayesian network meta-analysis (NMA) aimed to assess the relative safety profile of first-line targeted therapies (acalabrutinib, ibrutinib, obinutuzumab, ofatumumab, pirtobrutinib, ublituximab, umbralisib, venetoclax, zanubrutinib) in chronic lymphocytic leukaemia (CLL) patients with advanced age and/or comorbidities. The NMA revealed that zanubrutinib was the safest treatment option in terms of the overall safety profile (e.g., serious adverse events [AEs] grade 1-5), followed by venetoclax-obinutuzumab, which showed an advantage in terms of AEs grade 1-5. The use of Bruton\'s tyrosine kinase inhibitor (BTKi) monotherapy was more favourable in terms of the risk of haematological AEs, but chemoimmunotherapy showed advantages in terms of cardiovascular, gastrointestinal, and infectious AEs. The risk of secondary cancers was similar between treatments. In conclusion, targeted therapies are associated with variable and clinically relevant AEs. The therapies appear to be safer when used as monotherapy rather than in combination with immunological agents in naïve CLL patients with advanced age and/or comorbidities.