Need PD1

The purpose of this study is to identify clinical and molecular characteristics of melanoma patients that predict response to high-dose interleukin-2 (HD IL-2) in order to improve patient selection for this approved but toxic therapy.

We reviewed the records of 208 patients with unresectable stage III/IV melanoma treated with HD IL-2 at The University of Texas M.D Anderson Cancer Center (MDACC) (n=100) and Beth Israel Deaconess Medical Center (BIDMC) (n=108) between 2003 and 2009. The BRAF and NRAS mutation status of the tumors was determined for patients with available tissue samples and the mutation status and clinical characteristics were compared to clinical outcomes. Pre-treatment serum lactate dehydrogenase (LDH) levels were available for most patients (n=194). Tissue was available for mutational analysis on a subset of patients (n=103) and the prevalence of mutations was as follows: BRAF 60%, NRAS 15%, WT/WT 25%. In the subset of patients for which mutational analysis was available, there was a significant difference in the response rate based on the mutation status: NRAS 47%, BRAF 23%, and WT/WT 12% (p=0.05). Patients with NRAS mutations had non-statistically longer overall survival (5.3 versus 2.4 years, p=0.30) and progression free survival (214 versus 70 days, p=0.13). Patients with an elevated LDH had a decreased PFS (46 versus 76 days, p<0.0001), decreased OS (0.56 versus 1.97 years, p<0.0001), and trended toward a decreased response rate (7% versus 21%, p=0.08). NRAS mutational status is a new candidate biomarkers for selecting patients with melanoma for HD IL-2 treatment.

The purpose of this study is to identify clinical and molecular characteristics of melanoma patients that predict response to high-dose interleukin-2 (HD IL-2) in order to improve patient selection for this approved but toxic therapy.

We reviewed the records of 208 patients with unresectable stage III/IV melanoma treated with HD IL-2 at The University of Texas M.D Anderson Cancer Center (MDACC) (n=100) and Beth Israel Deaconess Medical Center (BIDMC) (n=108) between 2003 and 2009. The BRAF and NRAS mutation status of the tumors was determined for patients with available tissue samples and the mutation status and clinical characteristics were compared to clinical outcomes. Pre-treatment serum lactate dehydrogenase (LDH) levels were available for most patients (n=194). Tissue was available for mutational analysis on a subset of patients (n=103) and the prevalence of mutations was as follows: BRAF 60%, NRAS 15%, WT/WT 25%. In the subset of patients for which mutational analysis was available, there was a significant difference in the response rate based on the mutation status: NRAS 47%, BRAF 23%, and WT/WT 12% (p=0.05). Patients with NRAS mutations had non-statistically longer overall survival (5.3 versus 2.4 years, p=0.30) and progression free survival (214 versus 70 days, p=0.13). Patients with an elevated LDH had a decreased PFS (46 versus 76 days, p<0.0001), decreased OS (0.56 versus 1.97 years, p<0.0001), and trended toward a decreased response rate (7% versus 21%, p=0.08). NRAS mutational status is a new candidate biomarkers for selecting patients with melanoma for HD IL-2 treatment.

The purpose of this study is to identify clinical and molecular characteristics of melanoma patients that predict response to high-dose interleukin-2 (HD IL-2) in order to improve patient selection for this approved but toxic therapy.

We reviewed the records of 208 patients with unresectable stage III/IV melanoma treated with HD IL-2 at The University of Texas M.D Anderson Cancer Center (MDACC) (n=100) and Beth Israel Deaconess Medical Center (BIDMC) (n=108) between 2003 and 2009. The BRAF and NRAS mutation status of the tumors was determined for patients with available tissue samples and the mutation status and clinical characteristics were compared to clinical outcomes. Pre-treatment serum lactate dehydrogenase (LDH) levels were available for most patients (n=194). Tissue was available for mutational analysis on a subset of patients (n=103) and the prevalence of mutations was as follows: BRAF 60%, NRAS 15%, WT/WT 25%. In the subset of patients for which mutational analysis was available, there was a significant difference in the response rate based on the mutation status: NRAS 47%, BRAF 23%, and WT/WT 12% (p=0.05). Patients with NRAS mutations had non-statistically longer overall survival (5.3 versus 2.4 years, p=0.30) and progression free survival (214 versus 70 days, p=0.13). Patients with an elevated LDH had a decreased PFS (46 versus 76 days, p<0.0001), decreased OS (0.56 versus 1.97 years, p<0.0001), and trended toward a decreased response rate (7% versus 21%, p=0.08). NRAS mutational status is a new candidate biomarkers for selecting patients with melanoma for HD IL-2 treatment.