BACKGROUND:One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS). METHODS: An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS. RESULTS: Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded. CONCLUSIONS: The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials. Cancer 2011;117:1687-96.

The addition of oblimersen to dacarbazine significantly improved multiple clinical outcomes in patients with advanced melanoma and increased overall survival in patients without an elevated baseline serum LDH.

Purpose Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing Phase II clinical trial testing the efficacy of ACT using TIL in metastatic melanoma patients and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL followed by two cycles of high-dose (HD) IL-2 therapy. The effects of patient clinical features and the phenotypes of the T-cells infused on clinical response were determined. Results Overall, 15/31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC), with two patients (6.5%) having a complete response. Progression-free survival of >12 months was observed for 9/15 (60%) of the responding patients. Factors significantly associated with objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T-cells in the infusion product, a more differentiated effector phenotype of the CD8+ population and a higher frequency of CD8+ T-cells co-expressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in telomere lengths of TIL between responders and non-responders was identified. Conclusion These results indicate that immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in metastatic melanoma patients and that CD8+ T-cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.