Durable complete remission of leptomeningeal melanoma by intrathecal methotrexate maintained with systemic ipilimumab

Leptomeningeal disease (LMD) is a complication of metastasized melanoma, with poor prognosis even in the era of immunotherapy. We present the case of a 37-year-old man who was diagnosed with stage IV melanoma with lymphonodular, splenic and pulmonary metastases. Treatment with dabrafenib and trametinib led to a complete remission, but subsequent symptomatic LMD. Treatment was changed to intrathecal methotrexate, leading to aseptic meningitis, but also a remission of LMD. Followed by ipilimumab monotherapy, a durable, complete remission was observed. Symptomatic LMD may not be amenable to immunotherapy alone, as quick responses may be needed. With little evidence and few retrospective trials demonstrating the challenging treatment of LMD, intrathecal chemotherapy, potentially in combination, may still be considered a viable option.Lay abstract We present the case of a 37-year-old man who was diagnosed with advanced black skin cancer (melanoma) spread to other organ systems including the lung and the spleen. Oral, ‘targeted’ treatment with dabrafenib and trametinib led to the disappearance of all visible signs of cancer. However, the cancer reappeared and tumor cells were found in the cerebrospinal fluid, leading to nerve palsies and other neurological symptoms. This is a complication of advanced melanoma, with usually poor prognosis. The treatment was changed to methotrexate chemotherapy delivered into the cerebrospinal fluid, which lead to another remission. To maintain this cancer-free state, the patient was treated with subsequent intravenous ipilimumab, an immunotherapy supposed to induce an immune response against tumor cells, leading to a durable, cancer-free period of more than 6 years. The patient is still cancer-free to date.