Department of Research and Innovation, Haugesund Hospital, Helse Fonna Trust, Haugesund, Norway.
Blood. 2021 Mar 11;137(10):1295-1303. doi: 10.1182/blood.2019003809.
The last decades have seen great progress in the treatment of cold agglutinin disease (CAD). Comparative trials are lacking, and recommendations must be based mainly on nonrandomized trials and will be influenced by personal experience. Herein, current treatment options are reviewed and linked to 3 cases, each addressing specific aspects of therapy. Two major steps in CAD pathogenesis are identified, clonal B-cell lymphoproliferation and complement-mediated hemolysis, each of which constitutes a target of therapy. Although drug treatment is not always indicated, patients with symptomatic anemia or other bothersome symptoms should be treated. The importance of avoiding ineffective therapies is underscored. Corticosteroids should not be used to treat CAD. Studies on safety and efficacy of relevant drugs and combinations are briefly described. The author recommends that B cell-directed approaches remain the first choice in most patients requiring treatment. The 4-cycle bendamustine plus rituximab combination is highly efficacious and sufficiently safe and induces durable responses in most patients, but the time to response can be many months. Rituximab monotherapy should be preferred in frail patients. The complement C1s inhibitor sutimlimab is an emerging option in the second line and may also find its place in the first line in specific situations.
过去几十年见证了冷凝集素病 (CAD) 治疗方面的巨大进展。缺乏对照试验，因此建议主要基于非随机试验，并受到个人经验的影响。本文回顾了当前的治疗选择，并结合了 3 个病例，每个病例都涉及治疗的特定方面。CAD 发病机制中有两个主要步骤，即克隆 B 细胞淋巴增生和补体介导的溶血，这两者都是治疗的靶点。虽然并非总是需要药物治疗，但有症状性贫血或其他烦人的症状的患者应进行治疗。强调避免无效治疗的重要性。不应使用皮质类固醇治疗 CAD。简要描述了相关药物和联合用药的安全性和疗效研究。作者建议，在大多数需要治疗的患者中，针对 B 细胞的方法仍然是首选。在大多数患者中，4 周期苯达莫司汀联合利妥昔单抗具有高度疗效和足够的安全性，并可诱导持久反应，但反应时间可能需要数月。对于体弱患者，应优先选择利妥昔单抗单药治疗。补体 C1s 抑制剂 sutimlimab 是二线治疗的新选择，在某些情况下也可能在一线治疗中找到其位置。
