Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: Results of a randomized trial

Purpose : Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study. Patients and Methods: A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIIB and III melanoma compared with a control group treated only with surgery. Results: A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P =.068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%, respectively. Median RFS was 43 months in the control group compared with 83 months in the treated group (HR, 0.86; 95% CI, 0.7 to 1.07; P =.17). RFS at 5 years was 50.9% for the treated group and 46.8% for the control group. There were no selective benefits from the vaccine for particular subsets of patients. Conclusion: Immunotherapy with VMCL was not associated with a statistically significant improvement in OS or RFS, with CIs not ruling out important gains from such treatment.