From the AP-HP (A.P., N.V., C.B., G.B., D.P.), GH Pitié-Salpêtrière, Service de Neurologie 2-Mazarin, Paris, France; AP-HP (N.K.), Hôpital Cochin, Department of Dermatology, Paris, France; AP-HP (O.H.), Hôpital Necker, Department of Haematology, Imagine Institute, INSERM U1163, University of Paris, France; AP-HP (N.Z.), GH Pitié-Salpêtrière, Department of Pharmacology, Paris, France; Neurology Unit (G.B.), IRCCS San Raffaele Scientific Institute, Milan, Italy; and OncoNeuroTox Group (D.P.), Center for Patients with Neurological Complications of Oncologic Treatments, GH Pitié-Salpetrière et Hôpital Percy, Paris, France.
Neurol Neuroimmunol Neuroinflamm. 2021 Sep 8;8(6). doi: 10.1212/NXI.0000000000001073. Print 2021 Nov.
To describe the marked clinical and biological responses of a targeted treatment with anti-interleukin-6 (IL-6)-receptor antibody and Janus kinase (JAK) inhibitors in a patient with a severe, corticoresistant CNS toxicity of immune-checkpoint inhibitor (ICI) therapy.
A 58-year-old man was admitted for subacute paraparesis, urinary retention, and ascending paresthesia. He was under treatment with ipilimumab and nivolumab for metastatic melanoma. Spine MRI disclosed multiple T2-hyperintense, contrast-enhancing longitudinally extensive lesions. A diagnosis of ICI-related acute transverse myelitis was made.
ICIs were immediately discontinued, and the patient received high-dose glucocorticoids plus 1 session of plasma exchange, but he did not improve. Based on the marked elevation of CSF IL-6 (505 pg/mL), a second-line targeted therapy with anti-IL-6-receptor tocilizumab (8 mg/kg/mo for 3 infusions) plus JAK inhibitor ruxolitinib (50 mg/d) was administered. Patient neurologic status started to improve shortly after, with corresponding radiologic resolution. At 9 months, the patient was able to walk independently, presenting only slight residual disability while remaining in oncologic partial response.
Our case suggests that some patients with severe, corticoresistant CNS immune-related toxicities of ICIs may benefit from cytokine blockade. Cytokine measurement in serum and CSF might help in selecting patients for personalized treatment strategies.
描述一名接受抗白细胞介素-6（IL-6）受体抗体和 Janus 激酶（JAK）抑制剂靶向治疗的患者出现严重、皮质激素抵抗的中枢神经系统免疫检查点抑制剂（ICI）治疗毒性的显著临床和生物学反应。
一名 58 岁男性因亚急性截瘫、尿潴留和上升性感觉异常入院。他正在接受伊匹单抗和纳武单抗治疗转移性黑色素瘤。脊柱 MRI 显示多个 T2 高信号、对比增强的纵向广泛病变。诊断为 ICI 相关急性横贯性脊髓炎。
立即停止使用 ICI，患者接受了大剂量糖皮质激素加 1 次血浆置换，但未见改善。基于 CSF IL-6（505 pg/mL）明显升高，给予二线靶向治疗，使用抗 IL-6 受体托珠单抗（8 mg/kg/月，共 3 次输注）加 JAK 抑制剂鲁索利替尼（50 mg/d）。患者的神经状态在开始治疗后不久开始改善，影像学也随之得到缓解。9 个月时，患者能够独立行走，仅有轻微的残留残疾，同时保持肿瘤部分缓解。
我们的病例表明，一些患有严重、皮质激素抵抗的 ICI 相关中枢神经系统免疫毒性的患者可能受益于细胞因子阻断。血清和 CSF 中的细胞因子测量可能有助于为患者选择个性化的治疗策略。
