Rintatolimod (Ampligen(®)) 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. ABSTRACT: 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.