e20018 Background: Cutaneous melanoma incidence is rapidly rising in the elderly population. Imbalances of the immune system are described due to aging associated changes between CD4+, CD8+, T helper (Th) 1, Th 2 and T regulatory and T effector lymphocytes (lym). We describe clinical outcome in 10 elderly patients (pts) with cutaneous metastatic melanoma (CMM) and results of the immune studies done in a subgroup. Methods: Between October 2002 and October 2008, 10 elderly pts with treatment naïve CMM, 6 males and 4 female, median ages 76, range 57–84 years were treated at the University of Connecticut Health Center. Metastatic sites included soft tissue in 2 patients (pts), lung and/or liver with lymph node (LN) involvement (6 pts) and distant LN metastasis (2pts). Eight pts opted for treatment and received single or combination chemotherapy (5pts), high dose Interleukin 2 (2 pts), complete tumor resection followed by tumor derived heat shock protein vaccine (1 pt on clinical trial) and bio chemotherapy (1pt). One patient declined treatment (included in follow up). In vitro immune characteristics were studied in HLA-A2 positive subgroup (5pts) and included cytotoxic T lym (CTL) generation against self and non self peptides (Mart-1 27–35 and influenza MP derived peptide flu 58–66), proliferative activity of CD4+ lym in response to anti CD3 antibody under Th1 and Th2 conditions and regulatory T lym activity of CD4+CD25+ lym against CTL. Results: All patients tolerated treatments well resulting in 1 complete response, 4 partial responses, and 4 stable diseases. During 6 year follow up period, 6 patients died while 4 patients are living (one with disease). The median survival of all patients is 28.1 month (mo) while in those surviving (4pts) is 72 mo. Immune studies revealed preserved proliferative activity of CD4+ lym with stronger Th1 induction than Th2. The CTL responses to self and non self antigens were preserved while regulatory T lym showed weak activity against CTL. Conclusions: Some elderly patients with metastatic melanoma demonstrate improved outcomes and favorable immune characteristics. Further studies are needed to understand the impact of aging immune system on cutaneous melanoma. No significant financial relationships to disclose.