Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis

Zhe Zhao; Weike Zhang; Longbin Pang; Liangjie Zeng; Surui Liu; Jie Liu

doi:10.3389/fimmu.2023.1166299

Pancreatic adverse events of immune checkpoint inhibitors therapy for solid cancer patients: a systematic review and meta-analysis

Front Immunol. 2023 Jun 9:14:1166299. doi: 10.3389/fimmu.2023.1166299. eCollection 2023.

Authors

Zhe Zhao¹, Weike Zhang¹, Longbin Pang², Liangjie Zeng³, Surui Liu³, Jie Liu^{1

3}

Affiliations

¹ Department of Oncology, Jinan Central Hospital, Shandong University, Jinan, Shandong, China.
² Pulmonary and Critical Care Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
³ Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Abstract

Objective: This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.

Methods: We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis.

Results: 59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the post-hoc analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.

Conclusion: Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier 345350.

Keywords: drug-related adverse events; immune checkpoint inhibitors; immunotherapy; meta - analysis; pancreatic adverse events.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Amylases
Humans
Immune Checkpoint Inhibitors / adverse effects
Lipase
Neoplasms* / drug therapy
Pancreatitis* / chemically induced
Pancreatitis* / epidemiology

Substances

Immune Checkpoint Inhibitors
Amylases
Lipase

Grants and funding

This work was supported by the Natural Science Foundation of Shandong Province (ZR2020MH210).