A phase II trial of N-Acetyl-GM3/VSSP vaccine in high-risk resected melanoma patients (pts). Does vaccination modify melanoma outcome after relapse?

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3026 Background: Quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, representing an interesting target for anticancer therapy. Methods: Based on previous phase I study (Bitton et al, PASCO 2002, #1376), 38 high risk melanoma pts received N-Acetyl-GM3/VSSP vaccine in an adjuvant setting. Stage III: 8 pts, local-regional and systemic relapsed pts: 30 pts. All patients had no clinical evidence of disease. Five doses of 360 μg were given IM Q14D, 4 doses Q28D and then Q90D up to 2 years of treatment, relapse or unacceptable toxicity. Clinical outcome, humoral and cellular responses (Ig M anti-GM3, Ig G anti VSSP-GM3 and INFγ anti GM3 detected by Elispot) and toxicity (NCIC v2) were evaluated. Results: At a median follow-up of 35m (r: 7- 62 ), 28 pts (74%) relapsed and 23 (62%) are alive, most of them disease-free. One pt was lost at 7m. Median PFS was 8.5m (r:1–62). Median follow-up for alive pts is 49m (r:7–63).The estimated 5-year OS was 56% (95% CI: 34–76, Kaplan-Meier). Remarkably, many of the pts who relapsed were successfully rescued with local and/or systemic treatments, explaining the important gap between PFS and OS. Although serum reactivity to the vaccine (Ig G anti-VSSP-GM3) was observed in all patients, no specific humoral or cellular responses were detected. Mild to moderate local reactions, transient fever and asthenia were the most frequent toxicities observed. Five patients discontinued vaccination due to adverse events: post-vaccination G3 hypotension plus G3 ASAT/ALAT elevation (2); G2 injection site reaction (2); and syncope with uncertain relation to treatment (1). Conclusions: Compared to published data, observed OS was better than expected. N-Acetyl-GM3/VSSP vaccine might impact on the course of the disease through an antitumor effect or modulating responses to following treatments. The lack of specific immune response is probably due to the low immunogenicity of the ganglioside. Toxicity was acceptable. The immunomodulatory properties of GM3/VSSP warrants further investigation. No significant financial relationships to disclose.

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