Incidence of pancreatitis with the use of immune checkpoint inhibitors (ICI) in advanced cancers: A systematic review and meta-analysis

Authors

John George, Department of Internal Medicine, Bridgeport Hospital-Yale New Haven Health, Bridgeport, CT, USA.
Divyansh Bajaj, Department of Internal Medicine, Quinnipiac University Frank H. Netter MD School of Medicine/Saint Vincent Medical Center, Bridgeport, CT, USA.
Kesavan Sankaramangalam, Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School/Saint Peter's University Hospital, New Brunswick, NJ, USA.
Jin Woo Yoo, Department of Immunobiology Yale University School of Medicine, New Haven, CT, USA.
Nikhil S. Joshi, Department of Immunobiology Yale University School of Medicine, New Haven, CT, USA.
Scott Gettinger, Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA.
Christina Price, Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA.
James J. Farrell, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA. Electronic address: james.j.farrell@yale.edu.

Document Type

Article

Publication Title

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]

Abstract

BACKGROUND: Systemic immune side effects including pancreatitis have been reported with the use of Immune Checkpoint Inhibitors (ICI) (CTLA-4, PD-1 and PDL-1). However, the true incidence, risk, causes (tumor or drug specific) of pancreatitis and relation to other immune side effects, especially diabetes mellitus (DM) are unknown. METHODS: We performed a systematic review and meta-analysis of all clinical trials using ICI for the incidence of any grade lipase elevation, pancreatitis or DM. RESULTS: The incidence of asymptomatic lipase elevation after ICI use is 2.7% (211/7702) and grade 2 pancreatitis is 1.9% (150/7702). No pancreatitis related mortality has been reported in these clinical trials. Patients treated with CTLA-4 inhibitors have increased incidence of pancreatitis when compared to patients treated with PD1 inhibitors 3.98% (95% CI: 2.92 to 5.05) vs 0.94% (95% CI: 0.48 to 1.40); P value < 0.05. Patients treated with ICI for melanoma have increased incidence of pancreatitis when compared to non-melanoma cancers. We also noted an additive increase in incidence of pancreatitis with combination of CTLA4 and PD-1 inhibitors (10.60; 95% CI: 7.89 to 13.32) compared with either CTLA-4 or PD-1 inhibitors alone. CONCLUSIONS: Our study provides precise data for the incidence of pancreatitis among patients using ICI based on tumor types and ICI regimens. ICI use for solid tumors is associated with increased incidence of all grades of lipase elevation and pancreatitis, especially for CTLA-4 agents and ICI combination. Although it does not appear to be associated with mortality, ICI related pancreatitis should be recognized early for appropriate treatment and to potentially reduce long term complications.

First Page

587

Last Page

594

DOI

10.1016/j.pan.2019.04.015

Publication Date

6-1-2019

Recommended Citation

George, John; Bajaj, Divyansh; Sankaramangalam, Kesavan; Yoo, Jin Woo; Joshi, Nikhil S.; Gettinger, Scott; Price, Christina; and Farrell, James J., "Incidence of pancreatitis with the use of immune checkpoint inhibitors (ICI) in advanced cancers: A systematic review and meta-analysis" (2019). Systematic Reviews. 14.
https://scholar.bridgeporthospital.org/descriptive_study/14

Identifier

31076344 (pubmed); 10.1016/j.pan.2019.04.015 (doi); S1424-3903(19)30103-6 (pii)