Humoral shift and increased early recurrence with GM-CSF + vaccine versus vaccine alone

Abstract

3013 Background: Vaccines are currently under evaluation in melanoma, and many vaccine strategies use GM-CSF as an immune adjuvant. There are few randomized data yet available to determine the clinical impact of the addition of GM-CSF to vaccination. We conducted a randomized, prospective trial of an allogeneic melanoma vaccine with or without GM-CSF to determine the immune and clinical effects. Methods: 95 patients were stratified by stage and randomized to Canvaxin vaccine (with bacille Calmette-Guerin [BCG]) or Canvaxin (+BCG) and GM-CSF (200 mcg/m2/d) injected at the vaccine sites after vaccination for 5 days. Antibody titers against a urinary tumor-associated melanoma antigen were measured by ELISA, and DTH skin testing was done using PPD and unadulterated vaccine cells. Results: There was a significant early rise in both IgG and IgM titers in the GM-CSF arm with an early high plateau at about 8 weeks for both. The rise in antibody titer was slower in the non-GM-CSF arm with IgG rising throughout the study period and IgM peaking at 20 weeks. Conversely there was a delay in PPD responsiveness in the GM-CSF arm. PPD conversion percentage surpassed 90% in the non-GM-CSF arm at 6 weeks and peaked at 100% at 12 weeks. In the GM-CSF arm, only 76% converted at 6 weeks and only 87% were ever sensitized. A trend toward diminished DTH response was noted in the GM-CSF arm as early as 4 weeks and became significant at 16 weeks (p=0.01) and when considered throughout the trial. There was a marked increase in early recurrences in the GM-CSF arm leading to a significant survival difference when examined at 2 years (96% versus 72%; log-rank p=0.0017). Conclusions: When given at the site of vaccination, GM-CSF appears to accelerate the onset of a humor immune response while delaying cellular responses. In addition there appears to be evidence of adverse clinical effects in terms of early recurrence and possibly survival. Recent reports of increased myeloid suppressor cells with GM-CSF treatment may provide an immune mechanism for our findings. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration CancerVax