Tumor & Cancer Immunology and Immunotherapy

Biography

Biography: Maria Marcela Barrio

Abstract

Adjuvant treatment of high-risk cutaneous melanoma (CM) patients is still an unsolved issue. The CSF-470 therapeutic vaccine, a mixture of lethally irradiated allogeneic CM cell lines, combined with BCG and rhGM-CSF as adjuvants is currently tested in post-surgical adjuvancy against medium-dose IFN-α2b in stage IIB-III CM patients (CASVAC-0401 phase II-III study). Here we present the results of the phase II part of the study. Patients in the vaccine arm (n=20) received 1.6×107 CSF-470 melanoma irradiated cells i.d. plus 106 cfu BCG and 400 μg rhGM-CSF fractionated in 4 consecutive days were i.d. injected at the vaccination site, during 2 years (13 vaccinations in total). IFN-α2b patients (n=11) received 10 MU/day/5 days a week for 4 weeks; then 5 MU/day thrice weekly for 23 months (m). CSF-470 was well tolerated. The main toxicity was grade 2 reaction at the vaccination site (20/20); 3/20 patients presented grade 3 allergic reactions, easily handled with anti-histamines and corticosteroids; the rest of the AE were grade 1. IFN-α2b patients presented grade 2-3 hematologic (7/11), hepatic (2/11) and cardiac (1/11) toxicity, 9/11 patients developed AE that forced treatment discontinuation. QOL was significantly superior in CSF-470 arm vs. IFN-α2b arm. With a maximum follow-up of 72 m (Mean: 28 m) a significant benefit in the distant metastasis-free (DMF) survival for CSF-470 was observed (p=0.028). No significant differences in OS were yet observed. DTH reaction after the 7th vaccine was higher in distant metastasis-free patients than in progressing patients. Immune monitoring at 6 months showed an increase in NK cells (p=0.009) and a slight decrease in Tregs (p=0.021) in vaccinated patients; conversely IFN-α2b patients showed a significant decrease in total CD3+, CD4+ and CD8+T cells; serum Abs reactive with vaccine CM cells increased in all vaccinated patients (p<0.0001), but not in IFN-α2b patients. CSF-470 vaccine +BCG +GM-CSF superiority vs. IFN-α2b for adjuvant treatment of high-risk CM observed so far encourage continuation of the phase III part of CASVAC0401 study.