Lorlatinib Therapy for Rapid and Dramatic Control of Brain and Spinal Leptomeningeal Metastases From ALK-Positive Lung Adenocarcinoma

We report a patient with severe neurological deterioration due to leptomeningeal metastases involving brain and spinal cord from anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma, managed rapidly and successfully with lorlatinib therapy. A 48-year-old male patient presented with acute mental deterioration, severe headache, and weakness of both legs. The patient’s previous medical history included cerebral metastases from ALK-positive lung adenocarcinoma, which had been successfully managed via whole brain radiation therapy and gamma knife radiosurgery one year and three months before, respectively. Physical examination revealed neck stiffness and paraparesis with motor grade I. Gadolinium-enhanced brain MRI showed newly developed leptomeningeal enhancement along cerebellar folia, and whole spine MRI revealed similar leptomeningeal metastasis along the whole spinal axis. Lorlatinib was started orally with a dose of 100 mg/day. The patient showed rapid clinical improvement after one week. The patient was alert and the headache disappeared, while the paraparesis improved to normal ambulatory status. Two months of lorlatinib treatment resulted in almost complete disappearance of previous leptomeningeal enhancement of brain and spinal cord, and absence of newly developed metastatic lesions in the central nervous system, based on MRI results. The patient had been regularly followed with ongoing lorlatinib therapy for 5 months without any systemic complications or neurological abnormality. Conclusively, lorlatinib could be a rapid and effective treatment for patients with central nervous system leptomeningeal metastases arising from ALK-positive lung cancer.