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蛋白酶体抑制剂依赖的维持治疗对多发性骨髓瘤有效性和安全性的Meta分析:一项系统评价

Meta-analysis of effectiveness and safety of proteasome inhibitor-dependent maintenance treatment for multiple myeloma a systematic review.

作者信息

Yang Xin-Xin, Yao Guoli, Yang Yujing, Han Yahui, Yang Lin, Zhang Yuefeng

机构信息

First People's Hospital of Linping District, Hangzhou, China.

出版信息

Heliyon. 2024 Aug 13;10(16):e36311. doi: 10.1016/j.heliyon.2024.e36311. eCollection 2024 Aug 30.

Abstract

BACKGROUND

Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication.

METHODS

Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software.

RESULTS

Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P < 0.001) compared to placebo group, Serious adverse events (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01), Rash (OR: 2.23; 95 % Cl: 1.62, 3.05; P < 0.001) and Vomiting (OR: 5.12; 95 % Cl: 3.36, 7.80; P < 0.001). The Serious adverse events of the treatment group were remarkably greater compared with the untreated group (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01).

CONCLUSION

The study results proposed that proteasome inhibitors are effective in the multiple myeloma maintenance treatment compared with the placebo group. Bortezomib has certain advantages in prolonging PFS, followed by ixazomib and carfilzomib in terms of efficacy. Bortezombib may be superior to carfilzombib in extending OS. However, the adverse reactions caused by proteasome inhibitors, such as Peripheral neuropathy, Serious adverse events, Rash, Vomiting, etc., should be paid enough attention.

摘要

背景

尽管取得了重大进展,但多发性骨髓瘤(MM)的治疗仍然困难。目前,主要治疗方法包括干细胞移植联合治疗、药物治疗等。随着MM分子生物学机制的阐明,以及对骨髓瘤细胞内部信号和MM患者微环境的深入研究,越来越多靶向骨髓瘤和微环境的新药逐渐用于临床维持治疗,如蛋白酶体抑制剂:伊沙佐米、硼替佐米和卡非佐米,免疫调节剂:沙利度胺和来那度胺,单克隆抗体等在MM维持治疗中取得了很大进展。随着蛋白酶体抑制剂在MM维持治疗中的不断发展,该疾病的预后得到了显著改善。我们的目的是评估蛋白酶体抑制剂在多发性骨髓瘤维持治疗中的有效性和不良反应,为临床用药提供新思路。

方法

通过计算机检索四个包含蛋白酶体抑制剂在多发性骨髓瘤维持治疗有效性和安全性的随机对照研究的数据库。在对文献质量进行全面评估后,通过RevMan 5.3软件运行数据。

结果

最终本系统评价纳入8项研究。与安慰剂组相比,蛋白酶体抑制剂维持治疗多发性骨髓瘤患者可延长无进展生存期和总生存期。5项研究报告治疗组多发性骨髓瘤的周围神经病变与安慰剂组相比明显更多(OR:1.98;95%CI:1.35,2.92;P<0.001),严重不良事件(OR:1.60;95%CI:1.19,2.14;P<0.01)、皮疹(OR:2.23;95%CI:1.62,3.05;P<0.001)和呕吐(OR:5.12;95%CI:3.36,7.)。治疗组的严重不良事件与未治疗组相比明显更多(OR:1.60;95%CI:1.19,2.14;P<0.01)。

结论

研究结果表明,与安慰剂组相比,蛋白酶体抑制剂在多发性骨髓瘤维持治疗中有效。硼替佐米在延长无进展生存期方面有一定优势,其次是伊沙佐米和卡非佐米在疗效方面。在延长总生存期方面,硼替佐米可能优于卡非佐米。然而,蛋白酶体抑制剂引起的不良反应,如周围神经病变、严重不良事件、皮疹、呕吐等,应予以足够重视。 80;P<0.001)。治疗组的严重不良事件与未治疗组相比明显更多(OR:1.60;95%CI:1.19,2.14;P<0.01)。

结论

研究结果表明,与安慰剂组相比,蛋白酶体抑制剂在多发性骨髓瘤维持治疗中有效。硼替佐米在延长无进展生存期方面有一定优势,其次是伊沙佐米和卡非佐米在疗效方面。在延长总生存期方面,硼替佐米可能优于卡非佐米。然而,蛋白酶体抑制剂引起的不良反应,如周围神经病变、严重不良事件、皮疹、呕吐等,应予以足够重视。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c447/11382308/cee44e492113/gr1.jpg

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