IMCT-07THERAPEUTIC OUTCOMES OF INTRATHECAL INTERLEUKIN-2 IN METASTATIC MELANOMA PATIENTS WITH LEPTOMENINGEAL DISEASE (LMD)

Abstract

BACKGROUND: Melanoma patients with LMD have a median survival of 1.8 months; there is significant medical need for innovative therapeutic strategies. METHODS: Stage IV melanoma patients were diagnosed with LMD by positive CSF cytology and/or leptomeningeal enhancement on post-contrast MRI. Patients received treatment with 1-5 doses/week of intrathecal IL-2 (IT IL2) for 4 weeks, followed by weekly injections for 4 weeks, then every other week depending on tolerance and response. The patients were ultimately given maintenance dosing of a single injection every 1-3 months under FDA approved compassionate-use investigational new drug application. Log-rank tests and Cox proportional hazards regression were used to assess statistical significance. RESULTS: The median age among 42 pts (32 male, 10 female) was 46.7 years (range 18.8-71.0). Symptoms due to increased intracranial pressure developed initially in all pts, and were controlled with supportive medications and/or CSF removal. The median overall survival (OS) was 9.1 months (range 0.7 - 86.2); 16% of pts had OS > 24 mos. Pts with LMD only without extracranial disease (ECD) (n = 4) had a median OS of 38.4 months. Pts with LMD with controlled ECD (n = 19, median OS 11.0months) survived longer than pts with progressive ECD (n = 11, 6.5 mos; p = 0.30). Previous or concurrent brain metastases had no impact on OS. Shorter OS was associated with the presence of neurological symptoms at baseline (HR 2.1, p = 0.03). OS was not significantly associated with age, gender, LDH, or BRAF mutation status. CONCLUSIONS: The results support that IT IL2 can potentially improve the OS in a subset of pts, particularly those with no or controlled ECD, negative cytology, and no neurological symptoms. Furthermore, these results provide a strong rationale to evaluate IT immunotherapy in prospective clinical trials.