Abstract
BACKGROUND: Repetitive long-term Vaccinia Melanoma Cell Lysate (VMCL) vaccination schedules have proved clinically effective in producing Complete Responses and strong durable survivals for up to 6.1 years in a previous study of patients with advanced Stage IV and Stage IIIc melanoma. These studies were expanded to include 54 patients for further evaluation of these findings. METHODS: 54 patients comprising 48 Stage IV (6 M1a, 14 M1b, 28 M1c) and 6 advanced Stage III (5 IIIc; 1 IIIb) were studied using repeated intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued together with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was the primary end-point assessed, with clinical responses and toxicity recorded. RESULTS: From vaccine commencement, median overall survival was 14 months, ranging from 4 to 121 months. Kaplan-Meier survival analysis demonstrated overall 1, 2 and 3-year survival estimates of 57%, 26% and 18.5% respectively, and overall 5-year survival of 15.4%. No appreciable toxicity was observed. Complete Responses (CR) occurred in 16.7% (9) and partial responses (PR) in 14.8% (8) of patients. Stable disease was noted in a further 25 patients (46.3%). No response to therapy was apparent in 12 patients (22.2%). The overall response rate was 31.5% (CR + PR), with clinically significant responses (CR + PR + SD) in 77.8% of patients. Strong, durable clinical responses with overall survivals ≥ 23 months occurred in 29.6% of patients treated with repeated VMCL vaccine for advanced melanoma, (+/- concurrent chemotherapy). CONCLUSIONS: Prolonged, repetitive VMCL vaccination immunotherapy appears to be a clinically effective means of generating relatively high CR rates, useful clinical responses and long-term survivals, with little toxicity, but remains notably under-explored. Successive immunomodulation might explain the results. Closer analysis of repetitive dosing is required to improve clinical response rates and survival, perhaps by optimising the timing of immunotherapy delivery. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTRN12605000425695.