Intravenous immunoglobulin bridging to rituximab in NMDAR encephalitis patients non-responders to first-line treatments.

BACKGROUND: The immunotherapy strategy for autoimmune encephalitis is based on several types and schedules of both first- and second-line drugs. Failing to respond to the latter prompts the use of non-conventional rescue therapies, with higher risks of severe adverse effects. We report on a protocol that entails the use of intravenous immunoglobulin cycles to bridge the 4-month period that the second-line drug rituximab needs to exert its full therapeutic effects. METHODS: Three patients with NMDAR encephalitis who were non-responders to first-line treatments entered the study. The protocol consisted of six monthly cycles of intravenous immunoglobulins (IVIG, 0.4 mg/kg/die for 5 days), starting 1 month after the last rituximab infusion (1000 mg at days 0 and 15). Brain MRI and [18F]-FDG-PET were performed at onset and at six and 18 months after onset. RESULTS: In the three patients, substantial improvements of disability or complete recovery were achieved, without modifications over the 30-to-50-month follow-up. No adverse events nor laboratory test abnormalities were recorded. Imaging findings paralleled the favorable disease courses. Brain [18F]-FDG-PET was more sensitive than MRI in detecting abnormalities. DISCUSSION: Our observations suggest that the herein-described protocol might be used in patients with NMDAR encephalitis at risk for poor prognosis in the mid-term when they need to shift to rituximab. [18F]-FDG-PET confirmed to be a sensitive tool to detect the minimal brain lesions that can underlie isolated cognitive and psychiatric symptoms.

Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature.

INTRODUCTION: In the last years, many new drugs have been developed targeting different oncology pathways, overall improving both quality of life and survival in several malignancies. However, the increase of those therapies is associated with novel toxicities, mainly immune-related adverse events (irAEs), never observed before. Different irAEs are now well characterized, and, among them, neuromuscular complications, following immune checkpoint inhibitor (ICPi) therapy, are increasingly studied and described. However, there are also neurological complications related to the use of other targeted therapies, less known and probably underestimated. Herein we describe two oncological patients who developed neuromuscular diseases after administration of targeted therapies, different from ICPi. CASE REPORTS: The first patient was treated with the combination of Vemurafenib and Cobimetinib, BRAF and MEK inhibitors, respectively, for a cutaneous melanoma. One year after the beginning of the combined treatment, she developed a sub-acute motor neuropathy with predominant cranial nerve involvement. She was successfully treated with methylprednisolone. The second patient received therapy with Imatinib, tyrosine kinase inhibitor and precursor of the targeted therapy, for a gastrointestinal stromal tumour. Few days after the first administration, he developed generalized myasthenia gravis with respiratory failure. Clinical remission was obtained with plasma-exchange, intravenous immunoglobulins and steroids. DISCUSSION AND CONCLUSION: We strengthen the relevance of neuromuscular complications which may occur long after treatment start or in patients receiving not only the latest ICPi but also "older" and apparently better-known targeted therapies. Also in the latter cases, an immune-mediated "off-target" pathogenic mechanism can be hypothesized, and consequences can be life threatening, if not promptly diagnosed and appropriately managed.