免疫球蛋白轻链淀粉样变性：2026年诊断、预后和治疗的最新进展

摘要(中文译文)

AL淀粉样变性是一种克隆性浆细胞疾病，其中免疫球蛋白轻链或重链片段沉积于组织中。临床特征取决于受累器官，但可包括射血分数保留的心力衰竭、肾病综合征、肝功能障碍、周围神经病变/自主神经病变，以及“非典型冒烟型多发性骨髓瘤或意义未明的单克隆丙种球蛋白病”。需要采用刚果红染色的组织活检，显示淀粉样沉积物具有苹果绿双折射。85%的患者不需要进行器官活检。必须证实淀粉样物质由免疫球蛋白轻链组成。N末端脑钠肽前体（NT-proBNP或BNP）、血清肌钙蛋白T（或I），以及受累与未受累免疫球蛋白游离轻链值之间的差值，用于将患者分为四期；5年生存率分别为82%、62%、34%和20%。所有系统性淀粉样综合征患者均需接受治疗，以防止淀粉样物质沉积于其他器官并防止进行性器官衰竭。目前疗效最佳的一线治疗为达雷妥尤单抗、硼替佐米、环磷酰胺和地塞米松。治疗目标是达到≥非常好的部分缓解。对于未能达到此深度缓解的患者，巩固治疗选择包括泊马度胺、干细胞移植和维奈克拉。T细胞重定向疗法，包括双特异性抗体和CAR-T，显示出高水平活性，并可能很快成为标准二线治疗。延迟诊断仍然是在终末期器官衰竭发生之前启动有效治疗的主要障碍。一种用于清除沉积的κ纤维的抗体已在心肌病患者中报告具有获益。

Abstract

AL amyloidosis is a clonal plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include HFpEF, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS." Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5 year survivals are 82%, 62%, 34%, and 20% respectively. All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥ VGPR. In patients failing to achieve this depth of response, options for consolidation include pomalidomide, stem cell transplantation, and venetoclax. T-cell redirecting therapies, both bispecific antibodies and car T, show high level activity and may soon become standard second-line therapy. Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. An antibody to deplete deposited κ fibrils has reported benefit in patients with cardiomyopathy.

如何引用

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