Severe Adverse Events from Immune Checkpoint Inhibitor Therapy Are Rare

Lung cancer is the most common type of cancer and a leading cause of death worldwide.¹ Non–small-cell lung cancer (NSCLC) accounts for 85% of total cases, with small-cell lung cancer comprising the other 15%.¹ Locally advanced disease is found in approximately 33% of patients with NSCLC at diagnosis and has historically been treated with platinum-doublet chemotherapy.¹ Recent advances in therapies for advanced NSCLC have led to the use of immune checkpoint inhibitors, a form of immunotherapy that has improved clinical survival outcomes in lung cancer.¹ However, like standard chemotherapy, immune checkpoint inhibitors can cause treatment-related adverse effects such as colitis, hepatitis, endocrine organ dysfunction, or pneumonitis necessitating dose reduction, delaying treatment, and contributing to low patient adherence or discontinuation of treatment.¹

At the 2021 American Society of Clinical Oncology Annual Meeting, Luo and colleagues presented findings from a 2011 to 2020 review of pharmacy and patient records of those with advanced lung cancer treated with immune checkpoint blockade (ICB) to examine management and outcomes for treatment-related adverse events.²

During the review, 2750 patients with lung cancer were identified as being treated with ICB. Of these patients, 51 were treated with both steroids and an immunosuppressant for severe immune-related adverse events (irAEs). Colitis was experienced by 53% of patients, 20% developed pneumonitis, 12% developed hepatitis, and neuromuscular events were experienced by 10% of patients. Tumor necrosis factor α (TNFα) was the most used immunosuppressant (73%) followed by mycophenolate mofetil (20%).²

After 90 days post-treatment, most (57%) patients had improvement from their irAEs. Patients with hepatitis (n = 6) and colitis (n = 27) were more likely to experience improvement. No improvement was found in 18% of the patients, and 25% of the patients died. Mycophenolate mofetil (500-1000 mg twice daily) for a median of 3 months was used to treat all patients with hepatitis, and 5 of the 6 patients treated with this therapy improved. Colitis improved in 10 patients with just 1 dose of a TNFα. Patients with pneumonitis and neuromuscular irAEs were less likely to improve. Only 1 of 5 patients with neuromuscular adverse events improved, and 3 of 10 patients with pneumonitis improved.²

Toxicity related to the immunosuppression contributed to 4 deaths. Infection caused 3 deaths, while drug-induced liver failure caused 1 death. Prednisone (≥20 mg) was used for at least 3 weeks in 31 patients and caused side effects such as altered sleep or mood, weight gain, or infection in 28 patients. Mood or sleep disturbances were the most experienced side effect. Patients who died from immunosuppressive therapy received higher amounts of systemic steroids (525 mg vs 132 mg median prednisone dose) than patients who survived.²

While steroid-refractory/resistant irAEs during ICB therapy are rare, they were found to cause serious complications during this analysis of pharmacy records. The authors recommend more research into the pathophysiology of specific irAEs to help guide biologically informed treatment regimens for severe irAEs.²

References

1. Shao J, Wang C, Ren P, Jiang Y, Tian P, Li W. Treatment- and immune-related adverse events of immune checkpoint inhibitors in lung cancer. Biosci Rep. 2020;40(5):BSR20192347. doi:10.1042/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(15)9092. doi: 10.1200/JCO.2021.39.15.