Pulmonary Complications Secondary to Immune Checkpoint Inhibitors

Background Immune checkpoint inhibitors (ICI) have changed the landscape in the treatment of a number of cancers. Immune-related adverse events (irAEs) have emerged as a serious clinical problem with the use of ICI. Methods All oncology patients diagnosed with pulmonary complications secondary to ICI at Mayo Clinic Rochester from January 1, 2012 to December 31, 2018 were reviewed. Demographics, comorbidities, smoking, and oncologic history were analyzed. Results A total of 10 patients developed pulmonary complications secondary to ICI. Seven patients were men (70%), and the median age at diagnosis was 61.5 (IQR 55.8-69.3) years. All patients had stage IV disease. Melanoma was the most common malignancy. Seven (70%) patients had a positive smoking history, and 6 (60%) were obese (BMI > 30). Most cases were grade 2 pneumonitis (70%). One patient with grade 4 pneumonitis required endotracheal intubation and a prolonged course of systemic corticosteroids (>30 days). Eight (80%) patients received prior radiation therapy. The median time from initiation of ICI to pneumonitis diagnosis was 3.5 months. Conclusion Melanoma was the most common malignancy, the majority of patients had grade 2 pneumonitis and required treatment with steroids, and all patients affected by ICI-related pneumonitis had stage IV malignancy. Potential risk factors included smoking history, prior radiotherapy, obesity, and advance stage at the time of ICI initiation. Extrapulmonary irAEs are common in patients with pneumonitis.

[1]  R. Sullivan,et al.  Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis , 2018, JAMA oncology.

[2]  James R. Anderson,et al.  Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  N. Girard,et al.  Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients , 2017, European Respiratory Journal.

[4]  K. Shohdy,et al.  Risk of pneumonitis with different immune checkpoint inhibitors in NSCLC. , 2017, Annals of translational medicine.

[5]  J. Possick Pulmonary Toxicities from Checkpoint Immunotherapy for Malignancy. , 2017, Clinics in chest medicine.

[6]  C. Rudin,et al.  Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  T. Morimoto,et al.  Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer , 2016, PloS one.

[8]  Xinwei Zhang,et al.  PD-1 and its ligands are important immune checkpoints in cancer , 2016, Oncotarget.

[9]  A. Giobbie-Hurder,et al.  Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis. , 2016, JAMA oncology.

[10]  F. Hodi,et al.  PD-1 Inhibitor–Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course , 2016, Clinical Cancer Research.

[11]  P. Chanson,et al.  Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  Y. Abed,et al.  Obesity and inflammation: the linking mechanism and the complications , 2016, Archives of medical science : AMS.

[13]  O. Abdel-Rahman,et al.  Risk of pneumonitis in cancer patients treated with immune checkpoint inhibitors: a meta-analysis , 2016, Therapeutic advances in respiratory disease.

[14]  C. Rudin,et al.  Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. , 2015, The New England journal of medicine.

[15]  L. Crinò,et al.  Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. , 2015, The New England journal of medicine.

[16]  F. Hodi,et al.  Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab , 2015, Cancer Immunology Research.

[17]  Y. Nishioka,et al.  Characteristics of and Risk Factors for Interstitial Lung Disease Induced by Chemotherapy for Lung Cancer , 2015, The Annals of pharmacotherapy.

[18]  N. Agarwal,et al.  Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. , 2014, The Lancet. Oncology.

[19]  R. Dummer,et al.  Patterns of onset and resolution of immune‐related adverse events of special interest with ipilimumab , 2013, Cancer.

[20]  O. Gajic,et al.  Drug-associated acute lung injury: a population-based cohort study. , 2012, Chest.

[21]  M. Selman,et al.  Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. , 2012, American journal of respiratory and critical care medicine.

[22]  L. Walker,et al.  The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses , 2011, Nature Reviews Immunology.

[23]  Mohamed Karmali,et al.  Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention , 2010, Diabetes, metabolic syndrome and obesity : targets and therapy.

[24]  J. Dutcher,et al.  Managing toxicities of high-dose interleukin-2. , 2002, Oncology.

[25]  H. Schunkert,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Hormone Replacement Therapy and Interrelation between Serum Interleukin-6 and Body Mass Index in Postmenopausal Women: A Population-Based Study , 2022 .

[26]  R. Simsolo,et al.  The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. , 1995, The Journal of clinical investigation.

[27]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[28]  M. Lafontan Fat cells: afferent and efferent messages define new approaches to treat obesity. , 2005, Annual review of pharmacology and toxicology.