Association of low total lymphocyte count with overall and disease-free survival in patients with resected pancreatic adenocarcinoma receiving the GM-CSF secreting pancreatic tumor vaccine in combination with adjuvant chemoradiation.

Abstract

e14585 Background: Pancreatectomy, though necessary for potential cure of pancreatic ductal carcinoma (PDA), can be associated with immune dysregulation. Low total lymphocyte count (TLC) has been found to be a poor prognostic indicator in several different tumor types. The goal of this study was to determine whether low TLC could affect response to therapy and survival in resected pancreatic cancer patients who received a GMCSF-secreting cell-based tumor vaccine (GVAX) in addition to standard adjuvant therapy. Methods: Retrospective analysis of 60 patients enrolled in a phase II trial evaluating the safety, efficacy and immune activation of GVAX tumor vaccine administered in an adjuvant setting in resected PDA. Blood counts were analyzed from 8 weeks after surgery and then monthly after the completion of adjuvant chemoradiation. Results: The TLC just prior to the first vaccine was 1977 (range: 700-3890) and 10 patients had TLC < 1500. After adjusting for the prognostic factors identified in the original study (lymph node + and margin status), OS was significantly lower for those patients with TLC < 1500 (median 18.4 mos., 95% CI: 8.63 to infinity) as compared to those with TLC > 1500 (median 28.4 mos., 95% CI: 23.9 to 32.6, hazard ratio [HR] = 2.43, 95% CI: 1.09 to 5.41, p = 0.03). TLC < 1500 prior to first vaccine was also associated with shorter disease free survival (HR: 3.18 p < 0.01). Adjuvant chemoradiation consistently decreased TLC with a mean reduction of 1224 (range 450 to 2740). After adjuvant therapy, TLC < 500 was associated with reduced OS (HR: 4.86, 95% CI: 1.70 to 13.87, p < 0.01). Conclusions: Low TLC after surgery and after adjuvant chemoradiation is associated with poor survival in patients who receive pancreatic GVAX. This result suggests that immune suppressive conditions associated with current standard pancreatectomy and chemoradiation significantly compromise the efficacy of immunotherapy. Less invasive laparoscopic surgical approaches that result in less immune dysregulation and chemotherapy regimens that have lower immunosuppression should be considered.