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

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...

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Main Authors: Tian Zhang, Yi Wang, Chunhui Shi, Xiaochun Liu, Shangbin Lv, Xin Wang, Weihong Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.955701/full
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author Tian Zhang
Yi Wang
Chunhui Shi
Xiaochun Liu
Shangbin Lv
Xin Wang
Weihong Li
author_facet Tian Zhang
Yi Wang
Chunhui Shi
Xiaochun Liu
Shangbin Lv
Xin Wang
Weihong Li
author_sort Tian Zhang
collection DOAJ
description 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).
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spelling doaj.art-894d742a236240f286427f5603ae0f732022-12-22T02:23:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.955701955701Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysisTian Zhang0Yi Wang1Chunhui Shi2Xiaochun Liu3Shangbin Lv4Xin Wang5Weihong Li6Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBasic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Medical Oncology, Baoji Hospital of Traditional Chinese Medicine, Baoji, ChinaDepartment of Medical Oncology, Baoji Hospital of Traditional Chinese Medicine, Baoji, ChinaBasic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBasic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBasic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaBackground: 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).https://www.frontiersin.org/articles/10.3389/fphar.2022.955701/fullimmune checkpoint inhibitorsimmune-related adverse eventsmeta-analysispancreatic injurypancreatitisamylase
spellingShingle Tian Zhang
Yi Wang
Chunhui Shi
Xiaochun Liu
Shangbin Lv
Xin Wang
Weihong Li
Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
Frontiers in Pharmacology
immune checkpoint inhibitors
immune-related adverse events
meta-analysis
pancreatic injury
pancreatitis
amylase
title Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
title_full Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
title_fullStr Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
title_full_unstemmed Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
title_short Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis
title_sort pancreatic injury following immune checkpoint inhibitors a systematic review and meta analysis
topic immune checkpoint inhibitors
immune-related adverse events
meta-analysis
pancreatic injury
pancreatitis
amylase
url https://www.frontiersin.org/articles/10.3389/fphar.2022.955701/full
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AT xiaochunliu pancreaticinjuryfollowingimmunecheckpointinhibitorsasystematicreviewandmetaanalysis
AT shangbinlv pancreaticinjuryfollowingimmunecheckpointinhibitorsasystematicreviewandmetaanalysis
AT xinwang pancreaticinjuryfollowingimmunecheckpointinhibitorsasystematicreviewandmetaanalysis
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