Importance: The use of immune checkpoint inhibitors (ICIs) in the treatment of multiple cancers have gained prominence due to their high efficacy. However, neurological immune-related adverse events (irAEs) such as myasthenia gravis (MG) have been associated with ICI therapy. Most of these neurological irAEs are rare, and in many cases, their diagnoses and management can be challenging. Observations: We present a case of a 70-year-old woman with Stage IIIC melanoma who developed a new onset of gradually progressive dyspnea, diplopia, and bilateral ptosis following treatment with one cycle of nivolumab and ipilimumab (Nivo+Ipi). She was diagnosed with MG via positive serum acetylcholine receptor (AChR) antibodies. She had developed a severe dyspnea at rest, which was refractory to multiple immune-suppressive therapies including prednisone, pyridostigmine, and intravenous immunoglobulin (IVIG). Subsequently, she was treated with rituximab 375 mg/m2 monthly every 4 weeks with significant improvement of her symptoms within 48 hours each time.Conclusions and Relevance: As the implementation of immunotherapy increases in medical practice, irAEs may become more apparent. When first-line therapies are not adequate, other alternative therapies should be explored. This case of MG as an irAE shows that rituximab can provide potential benefit to treat patients with immunotherapy-induced MG who are refractory to other standard treatments. Prospective studies are needed to further evaluate the efficacy of Rituximab irAEs.
Immunotherapy agents such as ipilimumab and nivolumab are immensely effective in the treatment of various malignancies. Despite this, neurologic immune-related sequelae (NIRS) have been observed. Prompt diagnosis and treatment is critical to improve patient outcomes. We present a case of a 63-year-old man with stage IV metastatic melanoma beginning treatment with ipilimumab and nivolumab. Gathered history from the patient showed that he had a 3-year presentation of bradykinesia, shuffling gait, and muscle cramping. After one dose, the patient began to have progressively worsening generalized weakness; after receiving the immunotherapy, there was a rapid decline in his health. In addition to weakness, the patient developed diplopia, impaired single breath count, lingual and upper/lower extremity fasciculations, and brisk reflexes. While the lumbar puncture and myasthenia panel were non-diagnostic, the electromyography (EMG) revealed axonal neuropathy and diffuse denervation/reinnervation changes. Furthermore, a magnetic resonance imaging (MRI) displayed fatty replacement of the tongue with a bright tongue sign. These results pointed to the diagnosis of amyotrophic lateral sclerosis (ALS) superimposed onto myasthenic-like syndrome. The patient was started on various treatments; however, unfortunately he died due to acute hypoxic respiratory failure. This case highlights important considerations that must be taken when using immunotherapy, especially in patients with pre-existing neurological deficits. Furthermore, it shows the importance of early diagnosis as treatment can potentially cure adverse sequelae.
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