A Multidisciplinary Approach to Improve the Management of Immune-Checkpoint Inhibitor-Related Pneumonitis

Our plain-English summary of A Multidisciplinary Approach to Improve the Management of Immune-Checkpoint Inhibitor-Related Pneumonitis, by M. Valente, M. Colucci, V. Vegni, et al (OncoTargets and Therapy, 2024).

The study

• Authors: M. Valente, M. Colucci, V. Vegni, V. Croce, C. Bellan, G. Rossi, G. Gibilisco, F. Frongia, R. Guazzo, C. Ghiribelli, E. Bargagli, V. Savelli, M. Ravara, T. Sani, E. Simonetti, M. Maio, L. Calabrò, A.M. Di Giacomo
• Journal: OncoTargets and Therapy
• Published: 2024;17:673-681
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy.

Patients And Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification.

Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4-51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity.

Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN.

© 2024 Valente et al.

In plain English

This retrospective case series came from the University Hospital of Siena, Italy. It examined lung inflammation (immune-mediated pneumonitis) caused by cancer drugs called immune-checkpoint inhibitors. It did not study asbestos exposure; mesothelioma was one of the cancers treated. From January 2014 to February 2023, 1004 patients with melanoma (522), cutaneous squamous cell carcinoma (42), lung cancer (342) or mesothelioma (98) received these drugs. Of these, 24 (2%) developed pneumonitis, including 1 mesothelioma patient. Fourteen of the 24 had symptoms, mostly wheezing cough and shortness of breath. Cases were grade 1 (10) or grade 2 (14). Steroids led to resolution in 21 of the 22 patients who received them, with a median time to resolution of 14 weeks. Twelve patients restarted the drugs, and in 2 the pneumonitis came back. Lung-wash samples from 8 patients showed inflammatory cells. Electron microscopy in 2 patients showed findings suggestive of drug-related toxicity. The authors concluded that this side effect is rare and varied, and that multidisciplinary assessment helps manage it. They named the retrospective design and small sample size as limitations.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: retrospective case series
• Who was studied: 1004 patients treated with immune-checkpoint inhibitors at the Center for Immuno-Oncology, University Hospital of Siena, Italy, from January 2014 to February 2023: melanoma (522), cutaneous squamous cell carcinoma (42), lung cancer (342), mesothelioma (98). The 24 who developed pneumonitis were 18 melanoma, 1 cutaneous squamous cell carcinoma, 4 non-small cell lung cancer and 1 mesothelioma patient.
• Exposure: Immune-checkpoint inhibitor therapy (not asbestos): 619 patients (62%) received anti-PD1/PD-L1 monotherapy and 385 (38%) received it combined with other immunotherapy drugs (anti-CTLA4 or anti-indolamine 2,3-dioxygenase).
• Main results:
  • 24 of the 1004 treated patients (2%) developed immune-mediated pneumonitis.
  • Among the 24 patients with pneumonitis, the median time to onset was 46 weeks (range 2 to 312 weeks).
  • Of the 24 patients with pneumonitis, 14 (58%) had symptoms, most commonly wheezing cough (13) and shortness of breath (9).
  • Pneumonitis was grade 1 in 10 (42%) and grade 2 in 14 (58%) of the 24 patients.
  • CT patterns among the 24 patients were organizing pneumonia-like in 16 (67%), pulmonary eosinophilia in 7 (29%) and hypersensitivity pneumonitis in 1 (4%).
  • Among the 22 patients given steroids, pneumonitis resolved in 21 (95%), with a median time to clinical and/or radiological resolution of 14 weeks (range 0.4 to 51 weeks). No patient needed additional immunosuppressive therapy.
  • Immune-checkpoint inhibitor therapy was restarted in 12 patients (50%). Pneumonitis recurred in 2 of them, both with an organizing pneumonia-like pattern. Recurrence took longer to resolve (median 17 weeks, range 3 to 26) and led to permanent stopping of the drugs.
  • Bronchoscopy with lung-wash (BAL) analysis in 8 patients showed an inflammatory lymphocytic infiltrate, mainly foam cell-like macrophages in 6. Transmission electron microscopy in 2 patients showed multilamellar bodies, lysosomes and lipid vacuoles in alveolar macrophages, which the authors described as suggestive of drug-mediated toxicity.
• The authors' conclusion: The authors concluded that immune-mediated pneumonitis from immune-checkpoint inhibitor therapy was rare and challenging, with variable onset and varied clinical presentation. They concluded that multidisciplinary characterization helps optimize its management, reducing its severity and the delay in resuming therapy.
• Limitations the authors state:
  • Retrospective design and small sample size, which limit interpretation of the results.

Topics

Medical terms in this study, explained in our Lexicon: Multidisciplinary Team, checkpoint inhibitors, Pneumonitis, Immune-Related Adverse Events, Squamous Cell Carcinoma, Mesothelioma, Bronchoalveolar Lavage (BAL), Macrophage.

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