Ten-year analysis of vaccinia melanoma oncolysate (VMO) phase III trial.

Abstract

e19031 Background: We present a 10-year analysis of the first randomized, prospective, double-blind, multi- institutional melanoma vaccine trial with patients treated with either vaccinia melanoma oncolysate (VMO) or attenuated vaccinia virus (VV) between June 1988 and June 1991. Methods: Patient data was collected from eleven institutions over the course of trial, as well as from the Social Security Death Index. This data was analyzed in April 2008 for disease-free interval (DFI) and overall survival (OS) using log-rank analysis. Results: At time of analysis, 109 patients were evaluable with 78 patients living (35 VMO, 43 VV). The patients were divided as such: VMO_Alive, VV_Alive, VMO_Deceased, VV_Deceased. Gender-wise, 79% of females treated with VMO have survived, compared to 52% of males (p = 0.0473). There was no statistical significance among VMO- and VV-treated groups with reference to age (p = 0.3286), number of nodes (p = 0.6855), time (p = 0.5525), or size of lesion (p = 0.4008). Conclusions: This phase III trial was the first of its kind to employ a live attenuated vaccinia virus- augmented tumor cell vaccine (vaccinia oncolysate) as a specific active immune stimulator against advance stages of melanoma. The ensuing 10-year follow-up analysis shows no difference in patients who had received VMO compared to those who had received VV. But per FDA guidelines at the time, VV was originally designed as a negative control. The fact that VV had underlying activity made it difficult to interpret the efficacy of the vaccine. Moreover, our long-term results are in clear opposition to other melanoma vaccine trials, namely Morton (2005) and Hersey (2002). It should be noted that the first-generation melanoma vaccine demonstrated statistically-significant activity in males 44-57 years of age at time of initial analysis. Additionally, a significant number of patients from the original trial are alive at time of the 10-year analysis, demonstrating that there is an immune response generated by this vaccine. From this trial experience, we have developed a second-generation melanoma vaccine, which includes components from the first-generation melanoma vaccine, but is further enhanced to elicit a more potent immune response. No significant financial relationships to disclose.