• CTLA-4
• PD-1
• PD-L1
• immune checkpoint inhibitors
• immunotherapy
• metastatic melanoma
• treatment toxicity

• Humans
• Melanoma/drug therapy
• Melanoma/pathology
• Melanoma/immunology
• Immune Checkpoint Inhibitors/adverse effects
• Immune Checkpoint Inhibitors/administration & dosage
• Immune Checkpoint Inhibitors/pharmacology
• Neoplasm Metastasis
• Animals
• Fecal Microbiota Transplantation/methods
• Skin Neoplasms/pathology
• Skin Neoplasms/drug therapy
• Skin Neoplasms/immunology
• Adrenal Cortex Hormones/administration & dosage

• Immune Checkpoint Inhibitors
• Review

• Humans
• Abatacept/therapeutic use
• Adrenal Cortex Hormones/therapeutic use
• Colitis/chemically induced
• Colitis/drug therapy
• Hepatitis/drug therapy
• Immunoglobulins, Intravenous/therapeutic use
• Infliximab/therapeutic use
• Mycophenolic Acid/therapeutic use
• Myocarditis/drug therapy
• Neoplasms/complications
• Neoplasms/drug therapy
• Nitriles
• Pneumonia/drug therapy
• Pyrazoles
• Pyrimidines

• immunvermittelte gastritis
• autoimmungastritis
• typ a gastritis
• nicht-kleinzelliges bronchialkarzinom
• immuncheckpoint-inhibitor
• pembrolizumab
• immune-mediated gastritis
• autoimmune gastritis
• type a gastritis
• non-small cell lung cancer
• immune checkpoint inhibitor

• Female
• Humans
• Middle Aged
• Antibodies, Monoclonal, Humanized/adverse effects
• Gastritis/chemically induced
• Gastritis/diagnosis
• Gastritis/pathology
• Immune Checkpoint Inhibitors/adverse effects
• Lung Neoplasms/drug therapy
• Lung Neoplasms/pathology

• immune checkpoint inhibitors
• immune-related adverse events (IRAE)
• non-small cell lung cancer
• pneumonitis
• treatment

• National Key Research and Development Program of China
• National Natural Science Foundation of China
• China Postdoctoral Science Foundation

• ESMO Clinical Practice Guideline
• immunotherapy
• side-effects
• toxicity
• treatment

• Humans
• Follow-Up Studies
• Immunotherapy/adverse effects
• Immunologic Factors

• cancer immunotherapy
• drug induced pneumonitis
• immune-related adverse event (irae)
• infliximab
• non-small cell lung carcinoma (nsclc)

Severe pneumonitis induced by nivolumab, an anti-programmed cell death-1 monoclonal antibody, is a rare but potentially fatal immune-related adverse event. In cases of steroid-refractory pneumonitis, an appropriate therapeutic strategy using anti-tumor necrosis factor-α (TNF-α) antibody has not been established. A 59-year-old female was diagnosed with hypopharyngeal squamous cell carcinoma. Previous therapies including chemoradiotherapy and throat laryngectomy were performed, but metastatic recurrence appeared in the intrapulmonary and mediastinal lymph nodes. The patient was administered nivolumab. On the 14th day of nivolumab administration, the patient experienced dyspnea and computed tomography of the chest showed multiple consolidations in the right lung. She was diagnosed with nivolumab-induced pneumonitis. Because the pneumonitis was refractory to steroid therapy, she was administered infliximab, and the pneumonitis improved. On the 72nd and 101st days of nivolumab administration, nivolumab-induced pneumonitis re-appeared with an elevated serum TNF-α concentration. In each occurrence of pneumonitis, repetitive administration of infliximab improved the pneumonitis. Repetitive administration of infliximab may be effective for treating recurrent nivolumab-induced pneumonitis that is associated with an increased serum TNF-α concentration.

• head and neck cancer
• immunotherapy
• infliximab
• nivolumab
• pneumonitis

• case report
• checkpoint inhibitor pneumonitis
• pirfenidone
• steroid-resistance

• Aged
• Antibodies, Monoclonal, Humanized/administration & dosage
• Antibodies, Monoclonal, Humanized/adverse effects
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents, Immunological/administration & dosage
• Antineoplastic Agents, Immunological/adverse effects
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Drug-Related Side Effects and Adverse Reactions/drug therapy
• Humans
• Lung Neoplasms/drug therapy
• Male
• Pneumonia/chemically induced
• Pneumonia/drug therapy
• Pyridones/administration & dosage

• chemotherapy
• immunology
• lung cancer (oncology)
• pharmacology and therapeutics
• unwanted effects / adverse reactions

• Antibodies, Monoclonal, Humanized/adverse effects
• Carcinoma, Non-Small-Cell Lung/drug therapy
• Humans
• Lung Neoplasms/drug therapy
• Male
• Pneumonia/chemically induced

Since their discovery immune checkpoint inhibitors (ICI) have dramatically changed the treatment landscape for many cancers. In addition to their efficacy they are generally well tolerated, however, they have led to a new range of immune-related adverse events (irAEs) including pneumonitis. While not the most frequently reported immune-related adverse event in the clinical trial setting, recent real-world data suggests a significantly higher rate of pneumonitis leading to treatment suspension or cessation. It also appears to disproportionately contribute to immune-related mortality, particularly with anti-PD-1/PD-L1 treatment. While indicators have emerged regarding risk factors, incomplete prospective recording of patient characteristics hampers strong conclusions. Presenting symptoms are non-specific and the differential diagnosis is broad, made more complex by concomitant treatment with traditional chemotherapy or radiotherapy. Radiological findings are diverse and inconsistent terminology makes comparison and more complete characterization difficult. Further, little is known about the role of baseline testing or surveillance for early detection of pneumonitis, or the real-world role of bronchoscopy or biopsy in assessment. Scant literature exists to direct these complex decisions, so treatment guidelines have been published based on expert consensus. Here we provide a narrative review of what is known about ICI pneumonitis and propose key questions to enhance our understanding into the future.

• Pneumonitis
• checkpoint inhibitors
• immune-related adverse events

A 67-year-old man with stage IV B lung adenocarcinoma was treated with pembrolizumab. The patient was admitted to the hospital because of influenza on the day of the second cycle of pembrolizumab treatment. He was diagnosed with pneumonia and was treated with antiviral drugs and steroids. However, the patient eventually died. In this case, treatment with immune checkpoint inhibitors might have affected the immune response caused by influenza virus infection, that might have caused lung injury, which is an immune-related adverse event (irAE). Hence, it is important that, caution should be taken to prevent transmission of viral infection, and Therefore, it is important to prevent viral infections, but caution should also be paid to the possibility that infections may cause irAEs in patients with lung cancer.

• Immune checkpoint inhibitor
• Influenza virus
• Interstitial lung disease
• Lung cancer

Pembrolizumab is an anti-programmed death receptor 1 (PD-1) that was shown to have a tolerable safety profile with 17% of grade 3-4 drug-related adverse events, notable response rate of 16% with median duration of response of 8 mo, and median overall survival of 8 mo. Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported, and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering. We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.

An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo. She initially received 2 doses of ipilimumab 1 year ago with good outcome, but treatment was discontinued after developing severe diarrhea and rash. Pembrolizumab was then initiated 4 mo after disease progression. Significant improvement was noted after 3 doses. However, after 6 cycles of pembrolizumab, patient developed odynophagia and malnutrition. Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids. 3 mo later, patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen, finally ended up with intubation and tracheostomy. Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation, negative for malignancy and infection. Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.

We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab. The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids. The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.

• Pembrolizumab
• Infliximab
• Mucositis
• Melanoma
• Immunotherapy
• Refractory
• Case report

Immune checkpoint inhibitors (ICIs) have been applied to clinical practice and achieved significant therapeutic benefit in a variety of human malignancies. These drugs not only enhance the body’s antitumor immune response but also produce side effects called immune-related adverse events (irAEs). Although checkpoint inhibitor pneumonitis (CIP) has a low clinical incidence, it is likely to cause the delay or termination of immunotherapy and treatment-related death in some severe cases. An increasing number of CIP cases have been reported since 2015, which are attributed to the augmentation of approvals and uses of ICIs, but a comprehensive understanding of CIP is still lacking. This review focuses on the epidemiology, clinical characteristics, treatment strategies, and underlying mechanisms of CIP to strengthen the recognition of pulmonary toxicity among clinicians and researchers.

• immune checkpoint inhibitor
• immune-related adverse events
• pneumonitis
• programmed cell death 1
• programmed cell death ligand 1