INTRODUCTION
Metastatic melanoma, the most lethal among primary cutaneous neoplasms, poses significant challenges due to its depth of involvement and potential dissemination to lymph nodes and distant sites.1 Staging of melanoma is contingent upon these factors, with stage I and II denoting the absence of lymph node involvement or metastasis but differing in terms of their risk of recurrence. In contrast, Stage III melanoma involves regional lymph node metastases, while Stage IV is characterized by distant metastases, both of which are associated with lower survival rates. According to the SEER database, in 2018, individuals diagnosed with stage IV disease in the United States had a 5-year survival rate of 29.8%.2 Projections indicate a substantial increase in new cases of melanoma by 2030.3
BRAF inhibitors have demonstrated overall response rates ranging from 37% to 81%.5 As a result, the recommended first-line regimen for patients with BRAFV600-variant melanoma includes a combination BRAF and MEK inhibitor therapy with either dabrafenib and trametinib, vemurafenib and cobimetinib, or encorafenib and orbinimetinib.6 While checkpoint inhibitors have revolutionized management of metastatic melanoma, they come with a unique set of challenges. Checkpoint inhibitor induced neurotoxicity is a known adverse effect of checkpoint inhibitors that can be challenging to diagnose due to the varied presentation which may resemble myositis, polyneuropathy, myasthenia gravis, Miller Fisher syndrome, radiculoneuritis, and encephalitis among others.7,8,9
This is a rare description of checkpoint inhibitor induced neurotoxicity in the setting of metastatic melanoma. While no prospective studies have defined the optimal management for specific immune-related adverse events, several international guidelines exist.10 This case serves as a compelling example of the effective application of one such guideline.
One critical genetic determinant in melanoma pathogenesis is the v-raf murine sarcoma viral oncogene homolog B1 (BRAF), an essential component of the RAS-RAF-MEK-ERK mitogen–activated protein kinase (MAPK) cell signaling pathway. BRAF mutations have been identified in a substantial percentage of cutaneous malignant melanoma cases, making them a focal point for targeted therapy.4
BRAF inhibitors have demonstrated overall response rates ranging from 37% to 81%.5 As a result, the recommended first-line regimen for patients with BRAFV600-variant melanoma includes a combination BRAF and MEK inhibitor therapy with either dabrafenib and trametinib, vemurafenib and cobimetinib, or encorafenib and orbinimetinib.6 While checkpoint inhibitors have revolutionized management of metastatic melanoma, they come with a unique set of challenges. Checkpoint inhibitor induced neurotoxicity is a known adverse effect of checkpoint inhibitors that can be challenging to diagnose due to the varied presentation which may resemble myositis, polyneuropathy, myasthenia gravis, Miller Fisher syndrome, radiculoneuritis, and encephalitis among others.7,8,9
This is a rare description of checkpoint inhibitor induced neurotoxicity in the setting of metastatic melanoma. While no prospective studies have defined the optimal management for specific immune-related adverse events, several international guidelines exist.10 This case serves as a compelling example of the effective application of one such guideline.
CASE PRESENTATION
A 72-year-old male, Fitzpatrick skin type 3, presented to the hospital with right upper extremity weakness and neck pain after initiation of checkpoint inhibitor therapy.
The patient's medical history includes a history of nodular basal cell carcinoma of the right nasal ala, treated with successful
