Hairy cell leukemia (HCL) is an indolent B-cell malignancy with excellent initial response to purine analogs pentostatin or cladribine, but patients are rarely, if ever, cured. Younger patients will usually need repeat chemotherapy which has declining benefits and increasing toxicities with each course. Targeted therapies directed to the BRAF V600E mutation and Bruton’s tyrosine kinase may be helpful, but rarely eradicate the minimal residual disease (MRD) which will eventually lead to relapse. Moxetumomab pasudotox (Moxe) is an anti-CD22 recombinant immunotoxin, which binds to CD22 on HCL cells and leads to apoptotic cell death after internalization and trafficking of the toxin to the cytosol. Phase I testing achieved a complete remission (CR) rate of 57% in relapsed/refractory HCL. Most CRs were without MRD and eradication of MRD correlated with prolonged CR duration. Patients were often MRD-free after five years. Important mild-moderate toxicities included capillary leak and hemolytic uremic syndromes which could be prevented and managed conservatively. A phase 3 trial met its endpoint of durable CR with acceptable toxicity, leading to FDA approval of Moxe for relapsed/refractory HCL, under the name Lumoxiti. Moxe combined with rituximab is currently being evaluated in relapsed/refractory HCL to improve the rate of MRD-free CR.

中文翻译：

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毛细胞白血病重组免疫毒素的开发。

毛细胞白血病（HCL）是一种惰性的B细胞恶性肿瘤，对嘌呤类似物喷司他丁或克拉屈滨有极好的初始反应，但很少治愈。年轻的患者通常需要重复化疗，其每次疗程的益处都会降低，毒性增加。针对BRAF V600E突变和Bruton酪氨酸激酶的靶向疗法可能会有所帮助，但很少根除最终会导致复发的最小残留疾病（MRD）。假单抗Moxetumomab pasudotox（Moxe）是一种抗CD22重组免疫毒素，它与HCL细胞上的CD22结合并在毒素内化和运输到细胞质后导致凋亡性细胞死亡。I期测试在复发/难治性HCL中获得了57％的完全缓解（CR）率。大多数CR没有MRD，根除MRD与CR持续时间延长有关。五年后患者通常无MRD。重要的轻度-中度毒性包括毛细血管渗漏和溶血性尿毒症综合征，可以通过预防和保守治疗。一项3期试验达到了持久CR的终点并具有可接受的毒性，从而导致FDA批准Moxe用于复发/难治性HCL，名为Lumoxiti。目前正在复发/难治性HCL中评估与利妥昔单抗联合使用的Moxe，以提高无MRD的CR率。导致FDA批准Moxe用于复发/难治性HCL，名称为Lumoxiti。目前正在复发/难治性HCL中评估与利妥昔单抗联合使用的Moxe，以提高无MRD的CR率。导致FDA批准Moxe用于复发/难治性HCL，名称为Lumoxiti。目前正在复发/难治性HCL中评估与利妥昔单抗联合使用的Moxe，以提高无MRD的CR率。