Respiratory system toxicity induced by immune checkpoint inhibitors: A real-world study based on the FDA adverse event reporting system database

Cui, Chanjuan; Deng, Lei; Wang, Wenqing; Ren, Xiayang; Wang, Yanfeng; Cui, Wei

doi:10.3389/fonc.2022.941079

Cited by 5 publications

(3 citation statements)

References 54 publications

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“…Interstitial lung diseases and pneumonia were significantly associated with all ICIs. In addition, 7 of the 10 specific respiratory AEs (lower respiratory tract disease, pleural disease, pulmonary vascular disease, unclassified respiratory disease (NEC), respiratory infection, respiratory tumor, and chest disease) are associated with ICIs ( 117 ).…”

Section: Common Iraesmentioning

confidence: 99%

Immune-related adverse events of immune checkpoint inhibitors: a review

Yin

Han

et al. 2023

Front. Immunol.

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Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and the response rate and survival rate of many cancers have also been improved. Despite the success of immune checkpoint inhibitors, resistance limits the number of patients who can achieve a lasting response, and immune-related adverse events complicate treatment. The mechanism of immune-related adverse events (irAEs) is unclear. We summarize and discuss the mechanisms of action of immune checkpoint inhibitors, the different types of immune-related adverse events and their possible mechanisms, and describe possible strategies and targets for prevention and therapeutic interventions to mitigate them.

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Section: Common Iraesmentioning

confidence: 99%

Immune-related adverse events of immune checkpoint inhibitors: a review

Yin

Han

et al. 2023

Front. Immunol.

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“…First, we compared ICI regimens with high-frequency AEs reported from the whole database. ICI treatment strategies are associated Frontiers in Pharmacology frontiersin.org with a high incidence of toxicity in multiple organ systems, which are not limited to hematologic and lymphatic systems but also include the endocrine (Zhai et al, 2019), respiratory (Cui et al, 2022), hepatic (Remash et al, 2021), and renal systems (Hu et al, 2021). In our study, hematologic and lymphatic AEs were reported more frequently in patients treated with anti-PD-1/PD-L1 monotherapy than in those treated with anti-CTLA-4 monotherapy, with atezolizumab showing the strongest risk signal.…”

Section: Figurementioning

confidence: 99%

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Li,

Feng,

Chen

et al. 2023

Front. Pharmacol.

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Introduction: Immune checkpoint inhibitors (ICIs) exert antitumor responses in many types of cancer but may also induce serious or fatal toxicities that affect all organ systems, including the hematologic and lymphatic systems. However, the risk of hematologic and lymphatic system toxicities following different ICI treatments remains unknown. This study aimed to describe the hematologic and lymphatic system toxicities associated with different ICI regimens and the impact of combining ICIs with anti-vascular endothelial growth factor drugs using the United States Food and Drug Administration Adverse Event Reporting System pharmacovigilance database.Methods: The reporting odds ratio (ROR) and information component (IC) indices were used to identify disproportionate reporting of ICI-associated hematologic and lymphatic adverse events (AEs).Results: We extracted 10,971 ICI-associated hematologic and lymphatic AEs from 35,417,155 reports. These AEs were more frequently reported in female patients (ROR: 1.04 95% confidence interval [CI]: 1.01–1.07) and younger patients (ROR: 1.05 95% CI: 1.01–1.09). The disseminated intravascular coagulation fatality rate (63.97%) was the highest among the reported preferred terms, despite its low incidence (3.32%). The time to onset of ICI-related hematologic and lymphatic AEs was relatively short, with 77.44% reported within 3 months. Disproportionate analysis showed that most ICIs were associated with significant overreporting of hematologic and lymphatic AEs (IC025: 0.34 and ROR025: 2.10). Hematologic and lymphatic system AEs were more frequently reported in patients treated with anti-programmed cell death protein 1/programmed cell death ligand 1 monotherapy than in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 monotherapy (ROR: 1.54, 95% CI: 1.38–1.71), with atezolizumab showing the strongest signal (ROR025: 4.19, IC025: 1.00). In patients receiving combined treatment, ICIs plus bevacizumab exerted a higher disproportion signal than monotherapy (ROR: 161, 95% CI: 1.75–1.88).Discussion: The spectrum of hematologic and lymphatic AEs differed according to the ICI regimen. Early recognition and management of ICI-related hematologic and lymphatic AEs are vital in clinical practice.

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“…The analysis of spontaneous reporting databases, such as the FDA Adverse Even Reporting System (FAERS) and WHO Vigibase, allows a broader perspective by collecting unpublished reports of adverse events submitted all over the world occurring in real-world unselected subjects with comorbidities, poly-pharmacotherapy and complex anticancer combination regimens ( Raschi et al, 2020 ), which ensures rapid detection of even rare adverse events. Previous disproportionality analysis based on the FAERS database indicated that interstitial lung disease ( Guo et al, 2023 ), pulmonary tuberculosis ( Zhu et al, 2022a ) and pneumonitis ( Cui et al, 2022 ) were found to be significantly associated with ICIs exposure. But it is still unclear if ICIs were associated with increased reporting frequency of PJP in the real-world clinical setting.…”

Section: Introductionmentioning

confidence: 99%

Pneumocystis jirovecii pneumonia associated with immune checkpoint inhibitors: A systematic literature review of published case reports and disproportionality analysis based on the FAERS database

et al. 2023

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Background: Pneumocystis jirovecii pneumonia (PJP) has been reported with ICIs but limited to case reports. The clinical features of PJP with ICIs remain mostly unknown. This study aims to investigate the association of PJP with ICIs and describe clinical features.Methods: Reports of PJP recorded in FAERS (January 2004–December 2022) were identified through the preferred term “Pneumocystis jirovecii pneumonia”. Demographic and clinical features were described, and disproportionality signals were assessed through the Reporting Odds Ratio (ROR) and Information Component (IC), using traditional chemotherapy and targeted therapy as comparators, and adjusting signals by excluding contaminant immunosuppressive drugs and pre-existing diseases. A systematic literature review was conducted to describe clinical features of published PJP reports with ICIs. Bradford Hill criteria was adopted for global assessment of the evidence.Results: We identified 677 reports of PJP associated with ICIs, in which 300 (44.3%) PJP cases with fatal outcome. Nivolumab (IC025 2.05), pembrolizumab (IC025 1.88), ipilimumab (IC025 1.43), atezolizumab (IC025 0.36), durvalumab (IC025 1.65), nivolumab plus ipilimumab (IC025 1.59) have significant signals compared to other drugs in FAERS database. After excluding pre-existing diseases and immunosuppressive agents which may increase susceptibility of PJP, the signals for PJP associated with nivolumab, pembrolizumab, durvalumab, nivolumab plus ipilimumab remained robust (IC025 > 0). When compared to other anticancer regimens, although all ICIs showed a lower disproportionate signal for PJP than chemotherapy, nivolumab (IC025 0.33, p < 0.001), pembrolizumab (IC025 0.16, p < 0.001), both PD-1 inhibitors, presented a higher signal for PJP than targeted therapy. Male gender (IC025 0.26, p < 0.001) and age >65 years (IC025 0.38, p < 0.001) were predominant in PJP cases associated with across all ICIs. In literature, 15 PJP cases associated with ICIs were reported in 10 published case reports. 12 of 15 (80.0%) of cases received PD-1 inhibitors before PJP was diagnosed.Conclusion: By the combined analysis of post-marketing data from FAERS and published case reports, we identified ICIs may be associated with PJP, especially in males aged >65years. After accounting for confounders, PD-1 inhibitors emerged with a robust disproportionality signal when compared to PD-L1/CTLA-4 inhibitors as well as targeted therapy. Further research is warranted to validate our findings.

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Respiratory system toxicity induced by immune checkpoint inhibitors: A real-world study based on the FDA adverse event reporting system database

Cited by 5 publications

References 54 publications

Immune-related adverse events of immune checkpoint inhibitors: a review

Immune-related adverse events of immune checkpoint inhibitors: a review

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study

Pneumocystis jirovecii pneumonia associated with immune checkpoint inhibitors: A systematic literature review of published case reports and disproportionality analysis based on the FAERS database

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