A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

Abstract

We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL) was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL) was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days) followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs). However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately.

Clinical Experience of Immunotherapy Treatment: Efficacy and Toxicity Analysis of the Compassionate Use Program of Nivolumab in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer

“…In addition, we discovered other single cases of very rare AEs in our cohort. Cases of rhabdomyolysis [21] or Guillain-Barré syndrome [22] following nivolumab treatment have already been reported, but these are known neurological complications of PD-1 antibodies and rare AEs of immunotherapy treatment [23]. Many results concerning safety data between the phase 3 study of Brahmer et al [10] and our study are similar; however, the frequency of severe AEs was different.…”

Rhabdomyolysis during high dose interleukin-2 treatment of metastatic melanoma after sequential immunotherapies: a case report

“…Similarly, Sakai et al reported a case of a patient with metastatic melanoma treated with nivolumab who developed severe mononeuropathy multiplex and rhabdomyolysis. This patient did not have a pre-existing history of an underlying autoimmune condition and autoimmune serologies assessed after the onset of the patient’s symptoms were unremarkable [ 27 ].…”

Rhabdomyolysis following single administration of pembrolizumab: Is severe immune-reaction a marker for durable treatment response?

“…The above case is the first report describing severe immune-mediated myositis after a single dose of pembrolizumab. Katsuya et al encountered severe myositis with CK elevated to >27,000 U/L only 10 days after the first infusion; however, this was attributed to nivolumab ( Sakai et al, 2017 ). It is unclear if the same toxicity profiles apply to both nivolumab and pembrolizumab.…”