ABSTRACT
BACKGROUND: Leptomeningeal metastasis of melanoma is a devastating complication with a grave prognosis, and there are no known effective standard treatments. Although selective BRAF inhibitors have demonstrated a significant clinical activity in patients with metastatic melanoma harboring a BRAF mutation, the clinical benefit of BRAF inhibitor-based therapy in leptomeningeal disease is not clear. CASE PRESENTATION: We present a case of prolonged survival of a patient with BRAF V600E-mutant leptomeningeal disease who was treated with vemurafenib followed by whole brain radiation and a combination of dabrafenib and trametinib. Both vemurafenib and the sequential treatment of radiation and dabrafenib/trametinib led to regression of the leptomeningeal disease, and the patient survived for 19 months after the diagnosis of the leptomeningeal disease. CONCLUSION: This case suggests a possible clinically meaningful benefit of BRAF inhibitor-based therapy and a need for close investigation of this therapeutic approach in patients with this devastating disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Melanoma/genetics , Melanoma/pathology , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/secondary , Mutation , Proto-Oncogene Proteins B-raf/genetics , Antineoplastic Agents/administration & dosage , Humans , Magnetic Resonance Imaging , Male , Melanoma/diagnosis , Melanoma/metabolism , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/mortality , Middle Aged , Protein Kinase Inhibitors/administration & dosage , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Treatment OutcomeABSTRACT
We present a patient with metastatic BRAF-mutated melanoma who achieved long-term stabilization of leptomeningeal disease (LMD) with sequential whole-brain radiation therapy and vemurafenib. A 53-year-old woman with melanoma that harbored the BRAF V600E mutation and had that metastasized to multiple lymph nodes, lungs, breast, and subcutaneous tissue had developed symptomatic LMD 16 months after starting vemurafenib treatment despite achieving a substantial response at the existing metastatic sites. Vemurafenib was discontinued for 7 days, she received whole-brain radiation therapy (30 Gy in 10 fractions), and 7 days after completing the radiation therapy, she resumed vemurafenib therapy. The neurologic symptoms improved significantly, and a cerebrospinal fluid examination revealed disappearance of melanoma cells. She remained alive with radiologically stable LMD for at least 18 months after the whole-brain radiation therapy.
