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Checkpoint Inhibitor-Induced Pneumonitis: Incidence and Management

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Abstract

Purpose of Review

Despite immune checkpoint inhibitors’ (ICIs) many notable benefits, they carry the risk of immune-related adverse events (irAEs). Checkpoint inhibitor pneumonitis (CIP) is an irAE with significant morbidity and mortality. Early recognition and understanding of treatments are essential for those who prescribe ICIs or manage patients on therapy.

Recent Findings

Early detection of pneumonitis may be aided by increased serum CRP and IL-6 levels. Additionally, immunosuppressive treatment for patients failing steroids demonstrates that infliximab and tocilizumab provide some benefit, but outcomes remain poor. IVIG might be a better option.

Summary

CIP remains a challenging diagnosis. Certain risk factors have been identified for CIP development. Diagnosis is confounded by lack of pathognomonic radiology and pathology findings. Severity of disease guides treatment, which initially involves discontinuation of ICP and addition of steroids. For more severe cases, immunosuppression has a role but requires further study.

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Fig. 1

Adapted from Kalisz K, Ramaiya N, Laukamp et al. Immune checkpoint inhibitor therapy-related pneumonitis: patterns and management. RadioGraphics 2019;39:1923–1934 [4]

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Selected More Recent References of Interest

  1. Gatti-Mays M, Gulley JL. Real-world insights on preferred treatments for steroid-refractory immune checkpoint inhibitor-induced pneumonitis. J Immunother Cancer [Internet]. 2021 Feb 1 [cited 2023 Mar 26];9(2):e002252. Available from: https://doi.org/10.1136/jitc-2020-002252. This was a summary of treatment for steroid-refractory pneumonitis. It built on work by Balaji and Beattie (also reviewed and in the reference list above), which is helpful re: their experience with Infliximab and Mycophenolate mofetil, though I felt it left more questions than answers about optimal treatment.

  2. Wong A, Riley M, Zhao S, Wang JG, Esguerra V, Li M, et al. Association between pre-treatment chest imaging and pulmonary function abnormalities and immune checkpoint inhibitor pneumonitis. Cancer Immunol Immunother. 2023 Jan 14. Available from: https://doi.org/10.1007/s00262-023-03373-y. This was a retrospective study of patients who received at least dose of ICI. 46/1097 had CIP. Pretreatment PFTs and chest imaging were reviewed. Increased CIP seen with patients who had preexisting interstitial changes and reduced TLC. There is not much data on the role of screening and pretreatment PFTs but this study is intriguing that perhaps it should be more standardized to help risk-stratify patients re: best time to initiate ICI or whether to start at all.

  3. Lin X, Deng H, Chu T, Chen L, Yang Y, Qiu G, et al. Safety and efficacy of immunotherapy rechallenge following checkpoint inhibitor-related pneumonitis in advanced lung cancer patients: a retrospective multi-center cohort study. Transl Lung Cancer Res. 2022 Nov;11(11):2289–305. Available from: https://doi.org/10.21037/tlcr-22-732. A multicenter retrospective study of advanced lung cancer individuals who had grade ≥1 CIP and either received rechallenge with ICI or not. It demonstrated that grade ≥3 and ground glass opacity pattern had worse outcomes with rechallenge. Of 107 patients who were rechallenged, 9 had recurrent pneumonitis. This was an interesting study that also looked at factors of the recurrent pneumonitis patients and found that elevated white blood cell count as well as neutrophils and IL-6 and CRP levels in the serum portended higher recurrence rate. It provides some guidance on how to manage rechallenge in patients with CIP.

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  1. Department of Pulmonary, Critical Care and Sleep Medicine, Stony Brook Renaissance School of Medicine, Stony Brook, NY, USA

    Chaofan Yuan, Kunal Gada & Alpa G. Desai

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Kunal Gada and Chaofan Yuan declare that they have no conflict of interest. Alpa G. Desai has received speaker honorarium from Boehringer Ingelheim and Mallinckrodt.

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Yuan, C., Gada, K. & Desai, A.G. Checkpoint Inhibitor-Induced Pneumonitis: Incidence and Management. Curr Pulmonol Rep 12, 134–143 (2023). https://doi.org/10.1007/s13665-023-00314-z

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