Early tumour response assessment may avoid serious immune‐related adverse events in nivolumab and ipilimumab combination therapy for stage IV melanoma

Maeda, Takuya; Hiura, Azusa; Uehara, Jiro; Toyoshima, Rino; Nakagawa, Tomoe; Yoshino, Koji

doi:10.1111/bjd.20879

Cited by 4 publications

(1 citation statement)

References 9 publications

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“…However, ICIs are only effective in some patients and are prone to drug resistance ( Kaushik et al, 2022 ; Chen et al, 2022 ; Tong et al, 2021 ). Furthermore, most patients treated with ICIs develop immune-related adverse events (irAEs) ( Bertrand et al, 2015 ; Wang et al, 2019 ; Xu et al, 2018 ), some of which can be life-threatening ( Bagchi et al, 2021 ; Takamoto et al, 2022 ; Maeda et al, 2022 ; Wang et al, 2018 ). Since ICIs function by slowing down the immune activation process, they tend to exert off-target effects, including inflammation of different organs or tissues (Robert, 2020).…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Wang

Shi³

et al. 2022

Front. Pharmacol.

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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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Section: Introductionmentioning

confidence: 99%

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

Zhang

Wang

Shi³

et al. 2022

Front. Pharmacol.

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Combined use of nivolumab and ipilimumab in Japanese patients with melanoma: a multicentre retrospective study of 111 cases

Fujisawa

Namikawa²,

Yoshino

et al. 2023

British Journal of Dermatology

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New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events

Micevic

Daniels

Flavell

2023

British Journal of Dermatology

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Cutaneous side-effects associated with immune checkpoint-blockade occur in more than half of patients treated with aCTLA-4 and aPD-1 inhibitors and are frequently encountered by dermatologists. The molecular mechanism of cutaneous side-effects is incompletely understood but holds important clues about immune tolerance and the anti-tumor immune response in the skin. A new landmark study published in Nature suggests a critical functional role for the checkpoint receptor PD-1 in restraining self-reactive T cells, which could help explain how some checkpoint associated cutaneous side-effects arise.

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Early tumour response assessment may avoid serious immune‐related adverse events in nivolumab and ipilimumab combination therapy for stage IV melanoma

Cited by 4 publications

References 9 publications

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

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

Combined use of nivolumab and ipilimumab in Japanese patients with melanoma: a multicentre retrospective study of 111 cases

New insights into programmed cell death protein 1 blockade-associated cutaneous immune-related adverse events

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