Checkpoint Inhibitor Pneumonitis Induced by Programmed Death-1 Antibody: A Case Report and Literature Review

Review Article

J Stem Cell Res Transplant. 2021; 8(2): 1039.

Checkpoint Inhibitor Pneumonitis Induced by Programmed Death-1 Antibody: A Case Report and Literature Review

Zheng Y*, Li J, Chen D, Li Y, Dai L, Huang L, Wang M

Department of Oncology, Dalian Friendship Hospital, Liaoning Sheng, China

*Corresponding author: Yujun Zheng, Department of Oncology, Dalian Friendship Hospital, Dalian 116001, Liaoning Sheng, China

Received: May 20, 2021; Accepted: June 16, 2021; Published: June 23, 2021


Immune Checkpoint Inhibitors (ICIs) are effective treatment therapies for majority advanced tumours. However, the immune-related Adverse Events (irAEs) triggered by ICIs may affect human organs, including skin, lungs, pituitary, thyroid, blood and digestive system, leading to immunotoxicity in these organs. Checkpoint Inhibitor Pneumonitis (CIP) is one of the irAEs that could cause mortality, thereby needs special attention from the clinical physicians. In the present manuscript, the CIP occurred in a unilateral lung in one patient case with advanced oesophageal cancer treated with anti-PD-1 was analysed. Furthermore, a literature review was conducted to investigate its pathogenesis, clinical features, associated risk factors, prevention and the correlation with ICI efficacy, providing valuable information for clinical physicians.

Keywords: Programmed death-1; Pulmonary toxicity; Side effect; Checkpoint inhibitor pneumonitis


At present, immunotherapy has broken the bottleneck of the treatment in the treatment of advanced oesophageal cancer, providing effective treatment options for patients. The clinical usage of immunotherapy in treating advanced oesophageal cancer has been explored in the last decade, as first-line treatment, neoadjuvant and adjuvant therapy with surgery, as well as in real-world studies, showing its great potential. With the comprehensive clinical usage of the ICIs its irAEs appear to attract attention. According to a publication by Wang et al [1], irAEs occurred in 333 patient cases treated with ICIs such as anti-Programmed Death-1 (anti-PD-1) or anti–PD-1 ligand 1 (PD-L1) therapies. These irAEs included immunerelated pneumonitis (115 cases), hepatitis (74 cases), enteritis (58 cases), neuropathy (50 cases), heart disease (27 cases), myositis (22 cases) and blood system diseases (14 cases). Other rare irAEs included immune-related adrenal disease, nephritis, hypophysitis, thyroids, skin lesions and diabetes. Furthermore, two or more irAEs occurred in 51 patient cases. Of note, fatal irAEs happened 40 days (median time) after treatment initiation, with a mortality rate of 0.37%. The main fatal irAEs were immune-related pneumonitis and heart disease; therefore, the clinical physicians should be equipped with adequate information to improve the identification of clinical features, diagnosis and prevention of fatal irAEs. In the present manuscript, the mechanism, clinical features, prevention and risk factors of ICI-triggered Checkpoint Inhibitor Pneumonitis (CIP) were investigated, based on the one patient case with CIP caused by anti-PD-1, providing valuable information regarding the safety and effect of medications for clinical physicians.

Patient presentation

A 68-year old man with a body weight of 60 kg was admitted. In October 2012, he was diagnosed with space-occupying lesions in the upper esophagus and muscularis propria in the lower esophagus by the gastrointestinal biopsy showed differentiated squamous cell carcinoma. Subsequently, he underwent curative surgery. Postoperatively, moderately differentiated squamous cell carcinoma occurred in the esophagus, 3 cm from the upper resection edge, also invading submucosa and nerves. At 10 cm from the upper resection edge in the esophagus, invasive growth of poorly differentiated carcinoma was found in submucosal lymph nodes, expanding out of which and invading the esophageal squamous epithelium. The tumor cells were positive for P63, CK (AE1/AE3), and negative for CK7 and LCA. This patient was not treated with chemotherapy following surgery. In March 2020, the abdominal CT showed an upper-right abdominal lesion next to the stomach, with subsequent multiple enlarged lymph nodes at peritoneum. MRI scans confirmed multiple small nodules and lesion in soft tissues around the bottom of the stomach and peritoneum, indicating tumor reoccurrence. The patient was treated with sintilimab (200 mg, d1 ivgtt, q3w) in combination with albumin nab-paclitaxel (200 mg d1, 8 ivgtt) and cisplatin (40 mg d1, 8 ivgtt) for one week between 3rd April 2020 and 10th April 2020. Following the chemotherapy, this patient experienced intolerable grade III nausea and vomiting. Between 20th April 2020 and 21st May 2020, the patient was treated with sintilimab (200 mg, d1 ivgtt, q3w) in combination with albumin nab-paclitaxel (300 mg d1, ivgtt) for two weeks. Two weeks after the chemotherapy, there was a confirmed Complete Response (CR: disappearance of all lesions). The patient was under observation until 1st July 2021 (3 months after anti-PD-1 treatment), and showed symptoms of dry cough. His chest CT showed patchy shadow (Figure 1A), indicating CIP. Following treatment with 30 mg prednisone acetate once daily orally, the symptoms were relieved three days after treatment initiation. The drug dosage was consequently reduced to one tablet every five days until stopping the treatment. The chest CT showed that majority of the patchy shadow disappeared after more than ten days of treatment (Figure 1B). However, grade II rash occurred. Between 13th July 2020 and 21st August 2020, due to the increasing level of tumor markers, the patient was consequently treated with oral chemotherapy drug–tiggo (60 mg capsule, taken twice-daily d1-14, q3wk) for two weeks. Between 15th September 2020 and 29th October 2020, due to the continuously increasing level of tumor markers, this patient was treated with oxaliplatin (200 mg d1 ivgtt) combined with tiggo (60 mg capsule, taken twice-daily d1-14, q3wk) for two weeks. Over time, three events of CIPs occurred. The second, third and fourth events of CIP occurred on 19th August 2020 (4.5 months after immunotherapy initiation), 25th October 2020 (6.5 months after immunotherapy initiation) and 25th November 2020 (7.5 months after immunotherapy initiation). Which are shown in Figure 2, 3 and 4, respectively. The symptoms of all these CIP events were relieved following treatment of prednisone acetate using the same dosage as the first time. After the patient stopped the anti-PD-1 treatment, the tumor maker–CEA increased gradually, with no improvement in videography. The patient was in general good condition with no major adverse event reported. The progression-free survival achieved seven months in February 2021 (Figure 5).