Abstract
BackgroundRepetitive 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.Methods54 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.ResultsFrom 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).ConclusionsProlonged, 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 registrationAustralian and New Zealand Clinical Trials Registry ANZCTRN12605000425695.Electronic supplementary materialThe online version of this article (doi:10.1186/2051-1426-2-9) contains supplementary material, which is available to authorized users.
Highlights
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
Patients and inclusion/exclusion criteria Informed consent was obtained before entry into the study, which was approved by the Royal Adelaide Hospital Human Research Ethics Committee and was registered with the Australian Clinical Trials Registry [ACTRN 12605000425695]. 54 stage IV/IIIc advanced melanoma patients were enrolled in these studies for the primary aim
Primary endpoint – overall survival Overall survival for all 54 patients ranged from 4 months to 121 months
Summary
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. Survival of patients with advanced disseminated melanoma remains poor using almost any therapeutic means currently available In those relatively rare situations where surgery can be utilised in selected patients with metachronous or synchronous metastatic melanoma deposits, 5-year survivals of 5-35% have been reported [1,2,3]. The results of an initial pilot study using repeated doses of VMCL vaccine therapy in 37 patients with advanced surgically non-resectable stage IV/ IIIc metastatic melanoma demonstrated a CR rate of 18.9%, with strong durable survivals for up to 6.1 years, and survival rates of 40.5%, 21.6% and 10.8% at 1, 2 and 3 years respectively [15]
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