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Severe Adverse Events from Immune Checkpoint Inhibitor Therapy a Rare Concerning Side Effect

2021 Year in Review - Non–Small-Cell Lung Cancer

Lung cancer is the most frequent cancer and the leading cause of mortality worldwide.1 Non–small-cell lung cancer (NSCLC) accounts for 85% of all cases, whereas small-cell lung cancer accounts for 15%.1 At diagnosis, approximately 33% of patients with NSCLC have locally progressed illness, which has historically been treated with platinum-doublet chemotherapy.1 Immune checkpoint inhibitors, a type of immunotherapy, are a new therapy for patients with advanced NSCLC, and they have improved clinical survival results in patients with lung cancer.1 However, similar to regular chemotherapy, immune checkpoint inhibitors can produce treatment-related side effects such as colitis, hepatitis, endocrine organ dysfunction, or pneumonitis, which may necessitate dose reductions, treatment delays, or even treatment termination.1 Findings were presented at the 2021 American Society of Clinical Oncology Annual Meeting from a 2011 to 2020 review of pharmacy and patient records of patients with advanced lung cancer treated with immune checkpoint blockade to examine management and outcomes for treatment-related adverse events (AEs).2

Immune checkpoint blockade was used to treat 2750 patients with lung cancer who were identified during the review. For severe immune-related AEs, 51 of these patients were given steroids and an immunosuppressant. Patients had colitis in 53% of cases, pneumonitis in 20% of cases, hepatitis in 12% of cases, and neuromuscular problems in 10% of cases. The most frequently utilized immunosuppressant was tumor necrosis factor, followed by mycophenolate mofetil.2

Fifty-seven percent of patients reported improvement in their immune-related AEs after 90 days. Improvement was more likely in patients with hepatitis (N = 6) and colitis (N = 27). In 18% of patients, there was no improvement, and 25% of the patients died. All patients with hepatitis were treated with mycophenolate mofetil (500-1000 mg twice daily) for a median of 3 months, and 5 of 6 of these patients improved. For 10 patients, a single dose of tumor necrosis factor-α improved their colitis. Pneumonitis and neuromuscular immune-related AEs were associated with a lower likelihood of improvement. Only 1 of every 5 patients with neuromuscular AEs and 3 of every 10 patients with pneumonitis improved.2

Four patients died as a result of immunosuppression-related toxicity. Three patients died from infection, whereas 1 died from drug-induced liver failure. Prednisone (20 mg) was given to 31 patients for at least 3 weeks, and 28 of these patients had side effects such as changed sleep or mood, weight gain, or infection. The most common side effect was mood or sleep problems. Patients who died as a result of immunosuppressive medication used more systemic steroids (525 mg vs 132 mg median prednisone dose) than those who survived.2

Following this analysis, steroid-refractory/resistant immune-related AEs during immune checkpoint blockade therapy were discovered to cause significant complications. More research into the pathophysiology of individual immune-related AEs is needed, according to the researchers, to guide biologically informed treatment regimens for severe immune-related AEs.2


  1. Shao J, Wang C, Ren P, et al. Treatment- and immune-related adverse events of immune checkpoint inhibitors in lung cancer. Biosci Rep. 2020;40:BSR20192347.
  2. Luo J, Beattie J, Fuentes P, et al. Beyond steroids: immunosuppressants in steroid-refractory/resistant immune related adverse events. J Clin Oncol. 2021;39:Abstract 9092.

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