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      A potential mechanism of the onset of immune-related pneumonitis triggered by anti-PD-1 treatment in a patient with advanced adenocarcinoma lung cancer: case report

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          Abstract

          Background

          In recent years, the application of immunotherapy combined with chemotherapy in the first-line lung cancer has showed significant benefit in improving long-term survival. Immunotherapy also has risks of immune-related pneumonitis (IRP) after long-term treatment. Despite the treatment strategy of the IRP has been very clear. However, the mechanism is unclear.

          Case presentation

          A 73-year-old male patient was diagnosed with left lung adenocarcinoma IVa, EGFR, ALK, ROS1 negative. The patient received anti-PD1 antibody combined with pemetrexed and cisplatin. After 5 cycles of treatment, partial response was obtained. Subsequently, the patient continued the treatment of anti-PD1 antibody combined with pemetrexed. Before the 7th cycle, the CT found a new lesion in the basal segment of the right lower lobe. It was diagnosed with IRP and pneumocystis jirovecii. The patient did not give trimethoprim–sulphamethoxazole (TMP–SMX) and corticosteroids, symptoms and radiological lesions had improved. We describe the report of immune-related pneumonitis trigged by anti PD-1 and monitored the dynamic changes of CD 4+, CD 8+ T lymphocytes, MDSC and Treg cells in the bilateral bronchoalveolar alveolar lavage fluid. From the point of view of immune cells, the mechanism of immune reconstitution inflammatory syndrome is confirmed. Based on the current case report and literature, this study proposes a potential mechanism of the onset.

          Conclusion

          Immune reconstitution inflammatory syndrome may be potential mechanism of IRP. This study may improve our understanding of the pathogenesis underlying IRP. We believe the detection and dynamic monitoring CD4 +, CD8 + T lymphocytes, MDSC and Treg cells can provide more accurate procedures.

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          Most cited references17

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          Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials

          Yucai Wang, Shouhao Zhou, Fang Yang … (2019)
          Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
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            Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy.

            Jarushka Naidoo, Xuan Wang, Kaitlin M. Woo … (2017)
            Purpose Pneumonitis is an uncommon but potentially fatal toxicity of anti-programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Methods Patients who received anti-PD-1/PD-L1 monotherapy or in combination with anti-cytotoxic T-cell lymphocyte-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher's exact test as were associations between pneumonitis features and outcomes. Results Of 915 patients who received anti-PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5%; 95% CI, 3% to 6%; Memorial Sloan Kettering Cancer Center, 27 of 578 [5%]; Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%]; P < .01). Incidence was similar in patients with melanoma and non-small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%]; monotherapy, 15 of 417 v five of 152 [ P = 1.0]; combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment; proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were diverse. Conclusion Pneumonitis associated with anti-PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti-PD-1/PD-L1 mAbs are combined with anti-cytotoxic T-cell lymphocyte-4 mAb. Most events are low grade and improve/resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.
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              Immune Checkpoint Immunotherapy for Non-Small Cell Lung Cancer

              Karthik Suresh, Jarushka Naidoo, Cheng Lin … (2018)
              Immune checkpoint inhibitors (ICIs) are newer, immunotherapy-based drugs that have been shown to improve survival in advanced non-small cell lung cancer (NSCLC). Unlike traditional chemotherapeutic agents, ICIs work by boosting the body's natural tumor killing response. However, this unique mechanism of action has also led to the recognition of class-specific side effects. Labeled immune-related adverse events, these toxicities can affect multiple organ systems including the lungs. Immune-mediated lung injury because of ICI use, termed checkpoint inhibitor pneumonitis (CIP), occurs in about 3% to 5% of patients receiving ICIs; however, the real-world incidence of this entity may be higher, especially now that ICIs are being used in nonclinical trial settings. In this review, we briefly introduce the biology of ICIs and the indications for ICI use in NSCLC and then discuss the epidemiology and clinical and radiologic manifestations of CIP. Next, we discuss management strategies for CIP, including the current consensus on management of steroid-refractory CIP. Given the nascent nature of this field, we highlight areas of uncertainty and emerging research questions in the burgeoning field of checkpoint inhibitor pulmonary toxicity.
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                Author and article information

                Contributors
                Yu Feng: mozartfy@hotmail.com
                Cuncun Chen: ccc121501@126.com
                Liming Zhao: zhao.liming@hotmail.com
                Xuyou Zhu: tjzxy1210@163.com
                Xiaoping Zhu: z_xping@hotmail.com
                Qiang Li:
                ORCID: http://orcid.org/0000-0002-7502-6606
                seh_pulmonary@hotmail.com
                Journal
                Journal ID (nlm-ta): BMC Pulm Med
                Journal ID (iso-abbrev): BMC Pulm Med
                Title: BMC Pulmonary Medicine
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2466
                Publication date (Electronic): 14 September 2021
                Publication date PMC-release: 14 September 2021
                Publication date Collection: 2021
                Volume: 21
                Electronic Location Identifier: 291
                Affiliations
                [1 ]GRID grid.24516.34, ISNI 0000000123704535, Department of Respiratory Medicine, Shanghai East Hospital, , Affiliated to Tongji University, ; Shanghai, 200120 China
                [2 ]GRID grid.24516.34, ISNI 0000000123704535, Department of Clinical Laboratory, Shanghai East Hospital, , Affiliated to Tongji University, ; Shanghai, 200120 China
                [3 ]GRID grid.24516.34, ISNI 0000000123704535, Department of Pathology, Tongji Hospital, , Affiliated to Tongji University, ; Shanghai, 200438 China
                Author information
                http://orcid.org/0000-0002-7502-6606
                Article
                Publisher ID: 1649
                DOI: 10.1186/s12890-021-01649-6
                PMC ID: 8438889
                PubMed ID: 34521373
                SO-VID: 4fb2da5b-c2a3-427b-8b0c-625f3026ed5e
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 20 February 2021
                Date accepted : 30 August 2021
                Categories
                Subject: Case Report
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Respiratory medicine
                Keywords: immune-related pneumonitis,immune reconstitution inflammatory syndrome,anti-pd1,case report
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: immune-related pneumonitis, immune reconstitution inflammatory syndrome, anti-pd1, case report

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