Neoplastic leptomeningitis presenting in a melanoma patient treated with dabrafenib (a ^V600EBRAF inhibitor): a case report

Leptomeningeal metastases are occurring at higher frequency in cancer patients. The prognosis of leptomeningeal metastases is poor and standard treatment, which includes radiotherapy and chemotherapy, is mostly ineffective. Melanoma represents one of the tumors with the highest incidence of leptomeningeal metastases. For such a disease, the BRAF inhibitors have recently been demonstrated to be effective on melanoma brain metastases harboring the ^V600EBRAF mutation.

We report a case of a 39-year-old Italian woman with advanced melanoma with brain, lung and peritoneum metastases harboring the ^V600EBRAF mutation. In August 2010 she was enrolled into the BRIM3 trial and after the randomization process she received dacarbazine. After two cycles, there was evidence of disease progression in her peritoneum and lung. For this reason, she was enrolled into another clinical trial with the GSK2118436 BRAF inhibitor, dabrafenib, as a second line of therapy. She had a partial response that was maintained until 13 weeks of treatment. In January 2011 she developed symptoms typical for brain metastases and received a diagnosis of leptomeningeal involvement of melanoma cells after an examination of her cerebral spinal fluid; magnetic resonance imaging was negative for meningitis or brain metastases. Analysis of her cerebral spinal fluid sample confirmed that the melanoma cells still carried the ^V600EBRAF mutation. After a few days, our patient went into a coma and died.

Starting with a clinical case, we discuss the pathogenesis of leptomeningeal metastases and whether the leptomeninges may represent a sanctuary where melanoma cells may generate resistance and/or BRAF inhibitors cannot reach an adequate concentration for significant activity. We assess whether treatment with BRAF inhibitors in melanoma patients should be interrupted as soon as disease progression appears or continued beyond progression, through the administration of additional compounds.