Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​.

Keywords: chemotherapy; imm-101; immunotherapy; neoadjuvant chemoradiation; pancreatic adenocarcinoma.

Conflict of interest statement

The authors have declared financial relationships, which are detailed in the next section.

Figures

Figure 1. Duodenal pre-treatment biopsy

The patient’s duodenal pre-treatment biopsy demonstrating a typical poorly differentiated ductal adenocarcinoma with distorted glandular structures embedded in the desmoplastic stroma. Detail of pleomorphic non-polarised ductal epithelial cells forming glandular lumina containing inflammatory cells, mostly neutrophils, is seen.​

Figure 2. Post-treatment specimens

A1 – Pancreatic resection specimen demonstrating atrophic pancreatic parenchyma in which there are atrophic acini and scattered islets but no malignant elements; A2 – The parenchyma contains residual benign ducts with islets embedded in fibrovascular scarring reaction. Some of the ducts contain dystrophic calcific aggregates; B1 – Low power view of the liver resection demonstrates a subcapsular dense collagen scar with no glandular elements; B2 – Examination at higher power confirms there is dense collagen with no residual carcinoma.

Figure 3. Treatment timeline according to the CA19.9 levels

PR: partial response; PD: progressive disease; CR: complete response; RFA: radiofrequency ablation.