Rintatolimod (Ampligen(R)) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program

Simple Summary Survival of patients with locally advanced and metastatic pancreatic cancer remains poor after standard care with FOLFIRINOX. It is not known whether treatment with rintatolimod, a TLR-3 agonist, would improve progression-free survival. We investigated the immunomodulatory effects of rintatolimod and its benefits regarding progression-free and overall survival in patients who had been pre-treated with FOLFIRINOX. In long-term survivors (11 patients), we observed that rintatolimod treatment resulted in a lowering of the systemic immune-inflammation index (SIII) as well as the neutrophil to lymphocyte ratio (NLR), whereas peripheral B-cell counts were higher, when compared to short-term survivors (16 patients). Of note, rintatolimod treatment was associated with a higher progression-free and overall survival when compared to matched controls. These results support the effectiveness of adding rintatolimod as a maintenance therapy after FOLFIRINOX treatment in patients with advanced pancreatic cancer. A randomized controlled trial to further determine the efficacy of the drug is recommended. Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients' survival via immunomodulation, but the effect is unproven. Methods: In this single-center named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (<= 1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28-0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28-0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.