Oncotarget

Research Papers:

Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence

Kavin Sugumar, Andrew Alabd, Andre Alabd, Jonathan J. Hue, Josh Lyons, Sherri Fields, Zev Wainberg, Lei Zheng, Brianna Coogle, Anup Kasi, Nicholas Grewal, Hedy L. Kindler, Jason Starr, Ashwin R. Sama and Jordan M. Winter _

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Oncotarget. 2025; 16:427-442. https://doi.org/10.18632/oncotarget.28739

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Abstract

Kavin Sugumar1, Andrew Alabd2, Andre Alabd3, Jonathan J. Hue1, Josh Lyons1, Sherri Fields4, Zev Wainberg4, Lei Zheng5, Brianna Coogle6, Anup Kasi6, Nicholas Grewal7, Hedy L. Kindler7, Jason Starr8, Ashwin R. Sama9 and Jordan M. Winter1

1 Department of Surgery, University Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA

2 Department of Medicine, Cooper University Healthcare, Camden, NJ 08103, USA

3 Department of Urology, University of Indiana, Indianapolis, IN 46227, USA

4 Department of Medicine, UCLA/Santa Monica Cancer Center, CA 90404, USA

5 Department of Medicine, Johns Hopkins University, Baltimore, MD 21218, USA

6 Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66103, USA

7 Department of Medicine, University of Chicago, Chicago, IL 60637, USA

8 Department of Medicine, Mayo Clinic, Jacksonville, FL 32224, USA

9 Department of Medicine, Jefferson Medical Oncology Associates, Philadelphia, PA 19107, USA

Correspondence to:

Jordan M. Winter, email: [email protected]

Keywords: pancreatic adenocarcinoma; immunotherapy; exceptional responders; microsatellite instability; survival

Received: December 18, 2024     Accepted: May 17, 2025     Published: June 10, 2025

Copyright: © 2025 Sugumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Introduction: Immunotherapy has emerged as a standard treatment option for multiple solid tumors. However, most patients with pancreatic cancer (PC) do not derive a significant benefit. Identification and analyses of exceptional responders could eventually offer hints as to why PC is resistant to immunotherapy.

Methods: Oncologists from cancer centers in the United States were contacted to identify patients with PC who responded to immunotherapy. Exceptional responders were defined as those having either partial (PR) or complete response (CR) based on Response Evaluation Criteria in Solid Tumors, or biochemical response (CA 19-9 levels) after starting immunotherapy. Patients receiving concurrent chemotherapy were excluded.

Results: 14 patients met inclusion criteria. Immunotherapy drugs included checkpoint inhibitors and macrophage inhibitors. Eight patients (42%) were MSI (microsatellite instability)-high. Radiologically, 82% had PR. Four patients (28%) had marked reduction in CA 19-9. The median progression-free survival was 12 months from the start of immunotherapy. Median survival was not reached. The 1- and 2-year survival probabilities were 80%, 70% respectively.

Conclusion: Majority of clinical trials evaluating immunotherapy in PC have yielded disappointing response rates compared to other solid tumors. Our case series adds to published data from early-phase trials supporting the promise of immunotherapy in some patients with PC.


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