From the Centre National de Référence pour les Syndromes Neurologiques Paranéoplasiques (A.V., M.F., B.J., G.P., V.R., A.-L.P., S.M.-C., F.D., V.D., J.H.), Hospices Civils de Lyon, Hôpital Neurologique; Synatac Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France; University Claude Bernard Lyon 1, Université de Lyon; Service de Pneumologie-Oncologie Thoracique-Soins Intensifs Respiratoires (M.R.), Centre Hospitalier Universitaire de Rouen; Service d'Oncologie Médicale (J.R.), Institut de Cancérologie de l'Ouest René Gauducheau, St. Herblain; Service de Pneumologie (C.D.), Centre Hospitalier de Saint-Quentin; Service de Neurologie et Unité Neuro-Vasculaire-Hôpital de La Cavale Blanche (L.G.), Brest; Service de Neurologie et Unité Neurovasculaire (M.P.-G.), Centre Hospitalier Régional d'Orléans; Service de Neurologie-Pathologies Inflammatoires (J.L.), Centre Hospitalier Universitaire de Lille; and AP-HP (D.P.), Groupe Hospitalier Pitié-Salpêtrière, Service de Neurologie 2-Mazarin et Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), UMRS 975; Inserm U 975, CNRS, UMR 7225; Centre de Compétence des Syndromes Neurologiques Paraneoplasiques et Encéphalites Autoimmunes, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Neurol Neuroimmunol Neuroinflamm. 2019 Aug 7;6(6). doi: 10.1212/NXI.0000000000000604. Print 2019 Nov.
To report the induction of anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) in 6 patients after treatment with immune checkpoint inhibitors (ICIs). We also analyzed (1) patient clinical features compared with a cohort of 44 patients who developed Ma2-PNS without receiving ICI treatment and (2) the frequency of neuronal antibody detection before and after ICI implementation.
Retrospective nationwide study of all patients with Ma2-PNS developed during ICI treatment between 2017 and 2018.
Our series of patients included 5 men and 1 woman (median age, 63 years). The patients were receiving nivolumab (n = 3), pembrolizumab (n = 2), or a combination of nivolumab and ipilimumab (n = 1) for treatment of neoplasms that included lung (n = 4) and kidney (n = 1) cancers and pleural mesothelioma (n = 1). Clinical syndromes comprised a combination of limbic encephalitis and diencephalitis (n = 3), isolated limbic encephalitis (n = 2), and a syndrome characterized by ophthalmoplegia and head drop (n = 1). No significant clinical difference was observed between our 6 patients and the overall cohort of Ma2-PNS cases. Post-ICI Ma2-PNS accounted for 35% of the total 17 Ma2-PNS diagnosed in our center over the 2017-2018 biennium. Eight cases had been detected in the preceding biennium 2015-2016, corresponding to a 112% increase of Ma2-PNS frequency since the implementation of ICIs in France. Despite ICI withdrawal and immunotherapy, 4/6 patients died, and the remaining 2 showed a moderate to severe disability.
We show a clear association between ICI use and increased diagnosis of Ma2-PNS. Physicians need to be aware that ICIs can trigger Ma2-PNS because clinical presentation can be challenging.
报告 6 例接受免疫检查点抑制剂（ICI）治疗后出现抗 Ma2 抗体相关副肿瘤神经综合征（Ma2-PNS）的病例。我们还分析了（1）与未接受 ICI 治疗而发生 Ma2-PNS 的 44 例患者相比，患者的临床特征，以及（2）ICI 实施前后神经元抗体检测的频率。
对 2017 年至 2018 年间接受 ICI 治疗期间发生的 Ma2-PNS 患者进行了一项全国性回顾性研究。
我们的患者系列包括 5 名男性和 1 名女性（中位年龄 63 岁）。这些患者正在接受纳武单抗（n = 3）、派姆单抗（n = 2）或纳武单抗和伊匹单抗联合治疗（n = 1），用于治疗包括肺癌（n = 4）、肾癌（n = 1）和胸膜间皮瘤（n = 1）在内的肿瘤。临床综合征包括边缘脑炎和间脑炎的组合（n = 3）、孤立性边缘脑炎（n = 2）和以眼肌麻痹和头下垂为特征的综合征（n = 1）。我们的 6 例患者与 Ma2-PNS 总病例队列之间未观察到显著的临床差异。ICI 后 Ma2-PNS 占我们中心在 2017-2018 两年期间诊断的 17 例 Ma2-PNS 中的 35%。前两年 2015-2016 年已检测到 8 例，这表明自法国开始使用 ICI 以来，Ma2-PNS 的频率增加了 112%。尽管停用了 ICI 和免疫治疗，仍有 4/6 例患者死亡，其余 2 例患者仍存在中度至重度残疾。
我们证明了 ICI 使用与 Ma2-PNS 诊断率增加之间存在明确的关联。医生需要意识到 ICI 可能会引发 Ma2-PNS，因为其临床表现可能具有挑战性。
