Date of Graduation
Masters of Science (MS)
Michael A. Davies
BACKGROUND: Metastatic melanoma patients with leptomeningeal disease (LMD) have an extremely poor prognosis and a paucity of effective treatment options. We assessed the safety and efficacy of intrathecal interleukin-2 (IT IL-2) in metastatic melanoma patients with LMD.
METHODS: We reviewed the outcomes of 43 consecutive metastatic melanoma patients with LMD who were treated with IT IL-2 from 2006 to 2014 in a Compassionate Investigational New Drug Study. All patients had evidence of LMD based on cerebrospinal fluid (CSF) cytology, radiology, and/or surgical pathology. IL-2 at a dose of 1.2 mIU was administered intrathecally via Ommaya reservoir up to 5 times per week in the inpatient setting for 4 weeks; patients with good tolerance and clinical benefit received maintenance IT IL-2 every 1 to 3 months thereafter.
RESULTS: The median age of the patients was 46.7 years (range 18-71); 32 (74%) were male; 31 (72%) had positive CSF cytology, and 39 (91%) had radiographic evidence of LMD. Median overall survival (OS) from initiation of IT IL-2 was 7.8 months (range, 4.7-16.3 months), with 1-, 2-, and 5-year OS rates of 36%, 26%, and 13%. The presence of neurological symptoms (HR 2.1, p=0.03), positive baseline CSF cytology (HR 4.1, p=0.001) and concomitant use of targeted therapy (HR 3.0, p=0.02) were associated with shorter OS on univariate analysis. All patients developed symptoms due to increased intracranial pressure. There were no treatment-related deaths.
CONCLUSION: IT IL-2 treatment is safe and achieves long-term survival in a subset of metastatic melanoma patients with LMD.
melanoma, interleukin-2, intrathecal, leptomeningeal disease