From the Neurology Unit (F.C., M. Campagnolo, A.S., C.B.), Department of Neuroscience, University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; CEMES (M. Cacciavillani), Data Medica Group, Padova; and Immunology and Molecular Oncology (C.C., R.B.), Veneto Institute of Oncology IOV, IRCCS.
Neurol Neuroimmunol Neuroinflamm. 2020 Apr 13;7(4). doi: 10.1212/NXI.0000000000000720. Print 2020 Jul.
To assess whether neuropathy with anti-myelin-associated glycoprotein (MAG) antibody may improve after treatment with ibrutinib, an oral inhibitor of Bruton tyrosine kinase, we prospectively treated with ibrutinib a cohort of 3 patients with anti-MAG neuropathy and Waldenström macroglobulinemia (WM).
All 3 patients underwent bone marrow biopsy showing WM, with MYD88 mutated and CXCR4 wild type, and were started on ibrutinib 420 mg/die. Patients were assessed at baseline, at 3-6-9 months, and at 12 months in 2 patients with a longer follow-up, using Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score, INCAT sensory sum score, and Medical Research Council sum score. The modified International Cooperative Ataxia Rating Scale was performed in 2 patients, whereas it was not used in the patient with Parkinson disease as a major comorbidity. Responders were considered the patients improving by at least one point in 2 clinical scales.
All the patients reported an early and subjective benefit, consistent with the objective improvement, especially of the sensory symptoms as shown by clinical scales. Treatment was well tolerated.
These preliminary data point to a possible efficacy of ibrutinib in anti-MAG antibody neuropathy, which is the most common disabling paraproteinemic neuropathy, where active treatment is eagerly needed.
This study provides Class IV evidence that for patients with anti-MAG antibody neuropathy, ibrutinib improves neuropathy symptoms.
评估抗髓鞘相关糖蛋白（MAG）抗体相关性神经病在接受布鲁顿酪氨酸激酶（BTK）口服抑制剂伊布替尼治疗后是否会改善。我们前瞻性地治疗了 3 例抗 MAG 神经病伴瓦尔登斯特伦巨球蛋白血症（WM）患者。
所有 3 例患者均接受骨髓活检，显示 WM，MYD88 突变和 CXCR4 野生型，并开始每天服用 420mg 伊布替尼。在 2 例具有较长随访时间的患者中，在基线、3-6-9 个月和 12 个月时，使用炎症性神经病病因和治疗（INCAT）残疾评分、INCAT 感觉总分和医学研究委员会总分进行评估。在 2 例患者中进行了改良国际合作共济失调评分，而在 1 例伴有帕金森病的患者中未使用。应答者被认为是在 2 个临床量表中至少提高 1 分的患者。
所有患者均报告了早期和主观获益，与客观改善一致，尤其是临床量表显示的感觉症状。治疗耐受性良好。
这些初步数据表明伊布替尼可能对最常见的致残性副蛋白血症神经病——抗 MAG 抗体相关性神经病有效，这种疾病迫切需要积极治疗。
这项研究提供了 IV 级证据，表明对于抗 MAG 抗体神经病患者，伊布替尼可改善神经病症状。
