P2096 - Exceptional Responders to Immunotherapy in Pancreatic Cancer: A Multi-Institutional Case Series

Kavin Sugumar, MD¹, Andrew Alabd, MD², Andre Alabd, MD³, Jonathan Hue, MD¹, Sherri Fields, BS⁴, Brianna Coogle, BS⁵, Nicholas Grewal, BS⁶, Zev A. Wainberg, MD⁴, Anup Kasi, MD⁵, Jason Starr, DO⁷, Hedy Kindler, MD⁶, Lee M. Ocuin, MD⁸, Luke D. Rothermel, MD, MPH¹, Jeffrey M. Hardarce, MD¹, John B. Ammori, MD¹, Jordan M. Winter, MD^1
1University Hospitals Seidman Cancer Center and the Department of Surgery, Cleveland, OH; ²Cooper University Hospital, Camden, NJ; ³Indiana University Hospital, Indianapolis, IN; ⁴Ronald Reagan UCLA Medical Center, Los Angeles, CA; ⁵University of Kansas Medical Center, Kansas City, KS; ⁶University of Chicago Medical Center, Chicago, IL; ⁷Mayo Clinic, Jacksonville, FL; ⁸Atrium Health, Concord, NC

Introduction: Immunotherapy has emerged as an integral part of treatment regimens among numerous solid tumors, often conferring a significant survival benefit. However, most patients with pancreatic cancer (PAC) do not derive a similar survival benefit. We curate a list of rare but exceptional responders with PAC who had significant biochemical and radiological responses to immunotherapy.

Methods: Physicians from U.S. university hospitals and cancer centers were emailed to identify patients with PAC believed to have responded to immunotherapy. Exceptional responders were defined as those having either a complete response (CR) or partial response (PR) based on imRECIST imaging criteria and biochemical response (decreasing or stable trend of CA 19-9 levels). In all cases, immunotherapy was administered without chemotherapy, suggesting that the treatment was the principal response driver.

Results: Ten patients from 5 institutions met inclusion criteria (Table 1). All patients had pancreatic adenocarcinoma. Prior to immunotherapy, 4 patients (40%) had stage III, 2 patients (20%) had stage IV, and 4 patients (40%) had recurrent disease after resection. Four patients (40%) had MSI (microsatellite instability)-high tumors; the other six (60%) had MSI-stable tumors. Most (70%) patients received immunotherapy in a clinical trial, while 30% received off-label use. All patients had a PR on imaging. The median CA 19-9 level prior to immunotherapy was 74 IU/ml (range: 3-6400 IU/ml); the median level at the nadir during immunotherapy was 21 IU/ml (range: 1-273 IU/ml). Three patients experienced especially remarkable biochemical responses, with CA 19-9 levels reducing from 6400, 2030, and 776 IU/ml to 273, 43, and 3 IU/ml, respectively. Eight patients (80%) experienced adverse treatment effects. One patient (10%) discontinued therapy due to a grade 3 rash. The median progression-free survival and overall survival in the cohort were 12 and 16.6 months, respectively, from the start of immunotherapy, compared to 3.5 and 6 months historically in patients receiving second line chemotherapy.

Discussion: To date, no phase III studies have demonstrated the efficacy of immunotherapy for PAC, and few early phase studies reveal a promising signal. However, positive outliers exist and are not restricted to MSI-high tumors. These cases offer compelling evidence to support continued studies to identify predictive markers of immunotherapy response and treatment adjuvants to enhance the efficacy of these agents.

Case ID	Pathological diagnosis	Microsatellite instability (MSI)	Immunotherapy drugs used	Target	imRECIST criteria response (% decrease in sum of diameters of target lesion/s)	CA 19-9 prior to therapy (IU/ml)	CA 19-9 at maximal response (IU/ml)
1	Ductal adenocarcinoma	Stable	Nivolumab	PD-1	PR (N/A)	6400	273
2	Ductal adenocarcinoma	High	Pembrolizumab	PD-1	PR (65%)	24	8
3	Acinar cell cystadenocarcinoma	High	Pembrolizumab	PD-1	PR (76%)	3	1
4	Intraductal tubular neoplasm with invasive cancer	High	Pembrolizumab	PD-1	PR (60%)	127	67
5	IPMN with invasive cancer	Stable	Cabiralizumab	CSF-1R	PR (32%)	17	10
6	Mucinous cystic neoplasm with associated invasive cancer	High	Nivolumab	PD-1	PR (30%)	105	21
7	Ductal adenocarcinoma	Stable	Nivolumab + Cabiralizumab	PD-1 + CSF-1R	PR (42%)	7	7
8	Intraductal tubular neoplasm with invasive cancer	Stable	Pembrolizumab	PD-1	PR (50%)	2030	43
9	Ductal adenocarcinoma	Stable	Nivolumab + ipilimumab	PD-1 + CTLA4	PR (N/A)	776	3
10	Ductal adenocarcinoma	Stable	Atezolizumab	PD-1	PR (31%)	44	29

Table: Table 1. Patient characteristics


Disclosures:
Kavin Sugumar indicated no relevant financial relationships.
Andrew Alabd indicated no relevant financial relationships.
Andre Alabd indicated no relevant financial relationships.
Jonathan Hue indicated no relevant financial relationships.
Sherri Fields indicated no relevant financial relationships.
Brianna Coogle indicated no relevant financial relationships.
Nicholas Grewal indicated no relevant financial relationships.
Zev Wainberg indicated no relevant financial relationships.
Anup Kasi indicated no relevant financial relationships.
Jason Starr indicated no relevant financial relationships.
Hedy Kindler indicated no relevant financial relationships.
Lee Ocuin indicated no relevant financial relationships.
Luke Rothermel indicated no relevant financial relationships.
Jeffrey Hardarce indicated no relevant financial relationships.
John Ammori indicated no relevant financial relationships.
Jordan Winter indicated no relevant financial relationships.


Kavin Sugumar, MD¹, Andrew Alabd, MD², Andre Alabd, MD³, Jonathan Hue, MD¹, Sherri Fields, BS⁴, Brianna Coogle, BS⁵, Nicholas Grewal, BS⁶, Zev A. Wainberg, MD⁴, Anup Kasi, MD⁵, Jason Starr, DO⁷, Hedy Kindler, MD⁶, Lee M. Ocuin, MD⁸, Luke D. Rothermel, MD, MPH¹, Jeffrey M. Hardarce, MD¹, John B. Ammori, MD¹, Jordan M. Winter, MD¹. P2096 - Exceptional Responders to Immunotherapy in Pancreatic Cancer: A Multi-Institutional Case Series, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.