From the Department of Neuroscience (C.B., F.C.), University of Padova; Hematology and Clinical Immunology Unit (A.V., L.T.), Department of Medicine, University of Padova; and CEMES (M.C.), Data Medica Group, Padova, Italy.
Neurol Neuroimmunol Neuroinflamm. 2022 Jul 7;9(4). doi: 10.1212/NXI.0000000000001181. Print 2022 Jul.
Ibrutinib is active in anti-myelin-associated glycoprotein (MAG) polyneuropathy with MYD88 mutation; however, its efficacy is likely to be low in MYD88 wild-type patients. Venetoclax, an oral inhibitor of BCL2, in combination with rituximab is highly active in ibrutinib-resistant hematologic malignancies. We report on the first patient with anti-MAG polyneuropathy and MYD88 wild-type who responded to venetoclax-rituximab.
A 62-year-old woman with chronic lymphocytic leukemia had IgM/K anti-MAG neuropathy. She needed bilateral support to walk outdoors, despite therapy with rituximab/cyclophosphamide. Tremor and symptoms at arms prevented her capability of performing common tasks. Bone marrow genetic showed lack of MYD88 mutation. Venetoclax was given orally starting from 20 mg up to 400 mg for 24 months. Rituximab was administrated IV, after the ramp-up phase, at 375 mg/m for the second month and then monthly at 500 mg/m for months 3-7.
After 12 months of venetoclax IgM levels decreased from 1.16 to 0.52 g/L, the paraproteins became undetectable and anti-MAG antibody titer decreased. The patient regained the capability of walking independently. Tremor disappeared, she is back able to write and knitt.
The first patient with anti-MAG neuropathy treated with venetoclax-rituximab shows encouraging results.
This study provides Class IV evidence that for a patient with relapsed anti-MAG antibody polyneuropathy, MYD88 wild-type, venetoclax plus rituximab is effective.
伊布替尼在伴有 MYD88 突变的抗髓鞘相关糖蛋白（MAG）多神经病中具有活性；然而，在 MYD88 野生型患者中，其疗效可能较低。维奈托克，一种口服 BCL2 抑制剂，与利妥昔单抗联合用于伊布替尼耐药的血液恶性肿瘤具有高度活性。我们报告了首例对 MAG 多神经病和 MYD88 野生型有反应的维奈托克-利妥昔单抗患者。
一名 62 岁女性患有慢性淋巴细胞白血病，伴有 IgM/K 型抗 MAG 神经病。尽管接受了利妥昔单抗/环磷酰胺治疗，但她仍需要双侧支撑才能在户外行走。震颤和手臂症状使她无法进行日常活动。骨髓遗传学显示缺乏 MYD88 突变。维奈托克从 20 毫克开始口服，持续 24 个月，剂量增加至 400 毫克。利妥昔单抗静脉滴注，在爬坡期后，第 2 个月给予 375 毫克/平方米，第 3-7 个月每月给予 500 毫克/平方米。
维奈托克治疗 12 个月后，IgM 水平从 1.16 降至 0.52 g/L，副蛋白不可检测，抗 MAG 抗体滴度降低。患者恢复了独立行走的能力。震颤消失，她又能写字和编织了。
首例接受维奈托克-利妥昔单抗治疗的抗 MAG 神经病患者显示出令人鼓舞的结果。
这项研究提供了 IV 级证据，表明对于复发性抗 MAG 抗体多神经病、MYD88 野生型患者，维奈托克联合利妥昔单抗是有效的。
