Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review

IF 12.9 1区 医学 Q1 HEMATOLOGY Blood Cancer Journal Pub Date : 2024-11-07 DOI:10.1038/s41408-024-01182-9
Can Chen, Yiwei Li, Pengfei Shi, Shenxian Qian
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Abstract

Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remission in seven cases. The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation. In cases where diagnosis is challenging, kidney biopsy may assist if conditions permit. Comprehensive evaluation of the complement system, including genetic mutations, function, and associated complement inhibitory factor antibodies, should be included in the assessment of PI-TMA. Early administration of eculizumab may be beneficial in cases of suspected complement abnormalities or suboptimal response to initial treatments.

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蛋白酶体抑制剂相关血栓性微血管病:系统性综合回顾
蛋白酶体抑制剂(PIs)是治疗多发性骨髓瘤的关键,但也存在血栓性微血管病(TMA)的风险,尤其是使用卡非佐米时。本系统综述包括44项研究,涉及115例PI诱发的TMA,其中101例与卡非佐米有关。治疗方法各不相同:28 例患者接受了支持治疗,43 例接受了治疗性血浆置换(TPE),9 例仅接受了依库珠单抗(ECU)治疗,13 例同时接受了 TPE 和 ECU 治疗。值得注意的是,依库珠单抗明显改善了对初始TPE无反应的患者的治疗效果,7例患者的病情得到完全缓解。透析需求是预测预后的一个重要因素,往往预示着不良预后。对于怀疑患有 PI-TMA 的患者,即使没有得到实验室的明确证实,也应立即停用违规药物。在诊断困难的情况下,如果条件允许,肾活检可能会有所帮助。在评估 PI-TMA 时,应全面评估补体系统,包括基因突变、功能和相关的补体抑制因子抗体。在怀疑补体异常或对初始治疗反应不佳的病例中,及早使用依库珠单抗可能是有益的。
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来源期刊
CiteScore
16.70
自引率
2.30%
发文量
153
审稿时长
>12 weeks
期刊介绍: Blood Cancer Journal is dedicated to publishing high-quality articles related to hematologic malignancies and related disorders. The journal welcomes submissions of original research, reviews, guidelines, and letters that are deemed to have a significant impact in the field. While the journal covers a wide range of topics, it particularly focuses on areas such as: Preclinical studies of new compounds, especially those that provide mechanistic insights Clinical trials and observations Reviews related to new drugs and current management of hematologic malignancies Novel observations related to new mutations, molecular pathways, and tumor genomics Blood Cancer Journal offers a forum for expedited publication of novel observations regarding new mutations or altered pathways.
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