Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer

PMID: 38950309
Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (volume: 42, issue: 26, J Clin Oncol 2024 Sep;42(26):3083-3093)
Published: 2024-07-01

Authors:
van ‚t Land FR, Willemsen M, Bezemer K, van der Burg SH, van den Bosch TPP, Doukas M, Fellah A, Kolijn PM, Langerak AW, Moskie M, van der Oost E, Rozendaal NEM, Baart SJ, Aerts JGJV, van Eijck CHJ

ABSTRACT

PURPOSE: Immunotherapies have shown limited responses in patients with advanced pancreatic cancer. Recently, we reported that dendritic cell (DC)-based immunotherapy induced T-cell responses against pancreatic cancer antigens. The primary objective of this study was to determine the efficacy of DC-based immunotherapy to prevent recurrence of disease.

METHODS: This was a single-center, open-label, single-arm, combined phase I/II trial. The primary end point was the 2-year recurrence-free survival (RFS) rate. A 2-year RFS rate of ≥60% was defined as a clinically meaningful improvement. We included patients with pancreatic cancer after resection and completion of standard-of-care (SOC) treatment without recurrent disease on cross-sectional imaging. Patients were treated with autologous DCs pulsed with an allogeneic mesothelioma tumor cell lysate, comprising antigens also expressed in pancreatic ductal adenocarcinoma.

RESULTS: Thirty-eight patients were included in the analysis of the primary end point (47% male, 53% female). The median age was 62 years (IQR, 55-68). Twenty-eight patients (74%) received five DC vaccinations and completed the study protocol. Three patients (8%) received four vaccinations, and seven patients (16%) received three vaccinations. After a median follow-up of 25.5 months, 26 patients (68%) had not developed recurrence of disease. The estimated 2-year RFS was 64%. Vaccination led to the enrichment of circulating activated CD4+ T cells and the detection of treatment-induced immune responses in vitro. T-cell receptor-sequencing analyses of a resected solitary lung metastasis showed influx of vaccine-specific T cells.

CONCLUSION: This study reached its primary end point of a 2-year RFS rate of ≥60% following pancreatectomy after SOC treatment and adjuvant DC-based immunotherapy in patients with pancreatic cancer. These results warrant a future randomized trial.