Abstract This case presents a compelling example of managing leptomeningeal disease (LMD) in a patient with BRAF V600E mutant metastatic melanoma, demonstrating the potential efficacy of a triple-drug therapy approach in this complex clinical scenario. LMD is a rare but devastating complication of melanoma, typically associated with a poor prognosis. The 59-year-old female patient described here had advanced stage IV melanoma, with metastases to the lungs, kidneys, and brain. Initially, she was treated with systemic immunotherapy (IV ipilimumab/nivolumab), but this had to be discontinued due to severe pulmonary complications. Upon the development of metastatic brain lesions, the patient was treated with stereotactic radiosurgery, followed by whole-brain radiation at the time of disease progression. However, as her disease progressed to involve the leptomeninges, a more aggressive and tailored approach was necessary. In response, the patient was placed on a triple-drug regimen combining intrathecal nivolumab, along with the targeted therapies dabrafenib and trametinib. This combination approach led to a durable response, with the patient maintaining stability on therapy for seven months. This case highlights the promising role of combined approach utilizing systemic and intrathecal triple-drug therapy—targeting both the BRAF/MEK pathway and immune checkpoints—in managing patients with BRAF V600E mutant metastatic melanoma complicated by LMD. It underscores the importance of personalized treatment strategies, particularly for patients who are unable to tolerate standard systemic immunotherapies. Importantly, this case illustrates that rechallenging patients with intrathecal immune therapies, even after prior adverse effects or failure of systemic treatments, can lead to meaningful responses and disease stabilization. Furthermore, this case serves as an important reminder of the need for individualized care plans and the potential for long-term disease control in melanoma patients, even in the setting of complex and aggressive complications like LMD.
Maya Hrachova (Fri,) studied this question.