Infliximab for treatment-refractory transverse myelitis following immune therapy and radiation

Abstract

BackgroundNeurologic toxicities with immune therapy are rare, but can cause devastating and often permanent injury when they occur. Although there is increasing interest in the potential synergism between immune therapy and radiation, it is possible that such combinations may lead to a greater number or increased severity of immune-related adverse events. We present here a case of extensive and progressive transverse myelitis following combined therapy, which did not improve until treatment with infliximab. This case highlights the unmet need for treatment of adverse events that are refractory to consensus recommendations, and may ultimately require further study and incorporation into future published guidelines.Case presentationWe report a case of a 68-year-old with metastatic melanoma, who developed transverse myelitis in the setting of immune checkpoint blockade and spinal irradiation for vertebral metastases. Despite management according to published consensus guidelines: cessation of immune therapy, high-dose steroids, and plasmapheresis, he continued to deteriorate neurologically, and imaging revealed a progressive and ascending transverse myelitis. The patient was then treated with infliximab, and demonstrated dramatic imaging and modest clinical improvement following the first treatment cycle.ConclusionsThis is the first report describing the successful use of infliximab in immune therapy and radiation-related transverse myelitis that was not responding to recommended therapy. Evaluation of additional treatment options such as infliximab for high-grade immune-related neurologic toxicities is warranted, and may be needed earlier in the disease process to prevent significant morbidity. The adverse effects of immune therapy when used in combination with radiation also require further investigation.

Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke

“…Infliximab, a human and mouse chimeric monoclonal antibody that specifically blocks TNF-α, has been extensively used in clinic 22,23 . Addition of infliximab to the lower chamber (endothelial) of the co-culture system resulted in a significant reduction of the ratio of PI + /Hoechst + EC compared to that of the vehicle treated group under OGDR conditions (Fig.…”

Neurological immune‐related adverse events associated with immune checkpoint inhibitors: A review of the literature

“…We searched PubMed for ICIs‐related myelitis cases and identified 11 patients (Tables 2 and S4), 26,82‐91 seven (63.7%) of whom were males. The median onset age was 63 years (IQR: 51.5‐68; range: 35‐75).…”

Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature

“…Articles included in this review contained 23 case reports of patients who developed CNS demyelination after ICI administration. Of these cases, patients were classified as having the following syndromes: 7 with myelitis (19,(34)(35)(36)(37)(38)(39), four isolated optic neuritis (40)(41)(42)(43), one NMOSD (44), three had a relapse from a previously diagnosed MS (21,23,24), and two evolved from a radiologically isolated syndrome (RIS) to MS (22,45). Six patients had atypical demyelination (14,25,(46)(47)(48)(49).…”

“…We found seven case reports of myelitis associated with ICI. In four of them (34)(35)(36)(37), patients were exposed to radiotherapy on the cervical spine for bone metastases before (cases 7, 8, and 11) or during (case 10) ICI treatment. In all cases, delayed radiation myelopathy (DRM) was considered, but some features implicated an immune etiology, at least superimposed.…”