Primary leptomeningeal melanomatosis successfully treated with PD-1 inhibitor pembrolizumab

Abstract

Rationale: Primary leptomeningeal melanoma is an extremely rare disease of the central nervous system. There are no standard treatment protocols with a poor prognosis in very few reported cases. Immunotherapy in primary brain melanoma has not been successfully applied so far. Patient concerns: We describe a female patient 72-year-old diagnosed in the Neurosurgery Department which presented with generalized seizures. Diagnoses: Histological examination confirmed atypical melanocytes immunohistochemically positive for melan A, HMB45 and S-100 protein in the meninges, BRAF V600E negative. Dermatological, ophthalmological examinations, and 18-FDG PET/CT were negative. Interventions: The patient was successfully treated with pembrolizumab 2 mg/kg every 3 weeks for 2 years. Outcomes: The disease was stable for 2 years and the patient had no significant toxicity. Lessons: Our report describes durable intracranial tumor response suggesting the efficacy of PD-1 inhibitor pembrolizumab for central nervous system primary leptomeningeal melanoma.

The Role of Immune Checkpoint Inhibitors in Leptomeningeal Disease: A Systematic Review

“…The search yielded 289 citations, of which 14 were included in the qualitative synthesis (Supplementary File 1). Nine were case-reports, four were retrospective case-series (including 32 patients), and one was a single-arm phase-II trial (including 20 patients); levels of evidence were V, IV, and IIb, respectively (Supplementary File 2) (8)(9)(10)(11)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Critical appraisal resulted in low risk of bias for all included articles (Supplementary File 3).…”

“…Contrarily, mild radiotherapy adverse events (hair loss and skin reactions) occur in approximately 100% of patients, posing a significant cosmetic burden and affecting quality of life (3,37). Severe ICI-related adverse-events (headache, bone marrow depression) were reported in 5 patients (15.6%) but were successfully treated with temporary ICI discontinuation and/or addition of steroids (8,9,24). Of note, the use of steroids for mitigating ICI-related adverse events has not been correlated with a negative impact on survival (59).…”

Case Report: Differential Genomics and Evolution of a Meningeal Melanoma Treated With Ipilimumab and Nivolumab

“…In our case, the patient had adequate control of the disease after the use of adjuvant ipilimumab (10 mg/kg), and with ipilimumab/nivolumab after recurrence. Other recent reports have demonstrated the value of immunotherapy in patients with primary leptomeningeal melanomatosis and melanomas ( 25 ).…”

A case of primary meningeal melanocytosis treated with combination therapy with nivolumab and ipilimumab

“…2 Leptomeningeal metastases of melanoma have an extremely poor prognosis even with the use of BRAF inhibitors and immune checkpoint inhibitor immunotherapy. 3,4 In summary, we experienced a very rare case with meningeal melanocytosis. Although there are anecdotal case reports successfully treated with combination therapy with nivolumab and ipilimumab, 5 the patient did not respond to the treatment regimen.…”