Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis

Abstract

Background: Pancreatic injury (pancreatitis, amylase/lipase elevation) is a rare adverse event of immune checkpoint inhibitors (ICIs). With the high number of clinical studies on ICIs, the incidence and characteristics of associated pancreatic injury (PI) need to be reevaluated.Methods: A systematic review and meta-analysis was conducted to assess the incidence of PI in cancer patients who received ICIs in randomized controlled trials (RCTs). PubMed, Embase, the ASCO, ESMO, and AACR conference proceedings before 1 April 2022, were investigated for relevant research.Results: 50 RCTs involving 35,223 patients were included. The incidence of ICIs-PI was 2.22% (95% CI = 1.94%–2.53%). The incidence of PI was 3.76% (95% CI = 1.84–7.67%) when combining two ICIs, which was higher than single ICIs [2.25% (95% CI = 1.91–2.65%)]. The ICIs were ranked from high to low based on PI incidence: PD-L1 inhibitors 3.01% (95% CI = 1.86–4.87%), CTLA-4 inhibitors 2.92% (95% CI = 0.99–8.65%) and PD-1 Inhibitor 2% (95% CI = 1.67–2.39%). The ICI with the highest rate of PI was pembrolizumab 7.23.% (95% CI = 1.69–30.89%). In addition, the incidence of severe ICIs-PI was 2.08% (95% CI = 1.76–2.46%); and the incidence of severe PI was 2.32% (95% CI = 1.76–3.06%) when combining two ICIs, which was higher than single ICI [1.95% (95% CI = 1.58–2.41%)]. The ICIs were ranked from high to low according to the incidence of severe PI: PD-L1 inhibitors 3.1% (95% CI = 1.7–5.64%), CTLA-4 inhibitors 2.69% (95% CI = 0.76–9.49%), PD-1 inhibitors 1.80% (95% CI = 1.41–2.29%).Conclusion: Treatment with multiple ICIs result in a higher incidence of PI compared to single ICIs, irrespective of the grade of pancreatic injury. The incidence of PI caused by PD-L1 inhibitors is higher than that of CTLA-4 inhibitors and PD-1 Inhibitor, and Pembrolizumab has the highest rate of ICIs-PI. Although the incidence of ICIs-PI is not high, they are usually severe (≥ grade 3 events).

Pancreatic injury in patients treated with immune checkpoint inhibitors: a retrospective multicenterstudy

“…Some studies have reported on the risk factors for ICI-PI [ 16 , 17 , 19 , 32 ]. George et al reported that CTLA-4 inhibitors, combination therapy, and malignant melanoma were high-risk factors for ICI-PI [ 21 ].…”

“…On the other hand, the administration of ICIs is associated with immune-related adverse events (irAEs), which commonly involve the dermatologic, gastrointestinal, hepatic, pulmonary, and endocrine systems [11,12] and their management has been established [13,14]. However, pancreatic injuries are rare irAE manifestations of ICI administration [15][16][17][18][19][20], and their incidence, risk factors, treatments, clinical course, and associated OS are unclear. The National Comprehensive Cancer Network (NCCN) guidelines recommend continuation of ICI therapy in asymptomatic patients with pancreatic enzyme elevation with normal findings on pancreatic imaging [21].…”

Knowledge domains and emerging trends in immune-related adverse events from immune checkpoint inhibitors: A bibliometrics and visualized analysis

“…ICI-induced immunoassociated pancreatitis is currently a major area of focus in this field, which is a relatively uncommon irAE but has a high likelihood of being severe (≥ grade 3) [ 36 ] and potentially fatal [ 37 ]. It is characterized by serum amylase or lipase values greater than 3 times the upper limit of the normal value [ 38 ].…”

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

“…It has been postulated that the inflammatory status of ir exocrine pancreatitis triggers immune sensitization, which, in turn, may increase the risk of islet autoimmunity, but this hypothesis is unexplored [10,85]. Overall, due to the rarity of both irDM and ir pancreatitis, the explicit mechanisms underlying ir pancreatitis, irDM, and the interrelationship thereof remain elusive.…”