418. Peripheral Blood Leucocytes, Neutralizing Antibodies and Tumor Burden as Predictive and Prognostic Factors in Patients Treated with Oncolytic Adenoviral Immunotherapy

Oncolytic immunotherapy has taken significant steps towards clinical availability for cancer patients, as the FDA recently approved Imlygic (T-Vec) for the treatment of melanoma. Despite the several oncolytic virus trials, there are no known biomarkers which could predict the treatment outcome of oncolytic virotherapy. Therefore, previous clinical experiences should be utilized as guidance for further treatment optimization and patient selection. The patients analyzed consisted of 246 patients treated with oncolytic adenovirus as a part of the Advanced Therapy Access Program which was ongoing in Helsinki 2007-2012. Taken together with the increasing understanding that immunological factors might determine the efficacy of oncolytic virotherapy, we studied whether neutralizing antibodies and peripheral blood cell counts would have prognostic and/or predictive significance in the context of oncolytic adenovirus treatments. Additionally, tumor burden was assessed both in terms of primary tumor and metastases. We observed presence of neutralizing antibodies before treatment to be correlated with shorter overall survival (p=0.028). Blood cell counts analyses revealed that patients who had high neutrophil to lymphocyte ratio at baseline had significantly shorter overall survival (p<0.001). After treatment patients demonstrated transient lymphopenia and increases in neutrophils, which varied between disease control and progressive disease groups. Patients with high total tumor load had significantly shorter overall survival compared to low tumor load group (p=0.003). Interestingly, we also found presence of liver metastases to be correlated with reduced rate of disease control (p=0.021). These data indicate possible reasons behind the nonuniform treatment outcomes frequently observed after virotherapy. Moreover, our results suggest potential approaches for treatment refinement and patient selection in the context of oncolytic immunotherapy. Given the similarity of biological effects seen with different oncolytic DNA viruses, it will be interesting to see if these results will be similar in the context of other oncolytic viruses and cancer immunotherapy approaches such as adoptive T-cell therapy and cancer vaccines.