Impact of immune-related adverse events on survival among patients with head-and-neck squamous cell carcinoma

Immunotherapy. 2024;16(16-17):1069-1078. doi: 10.1080/1750743X.2024.2409617. Epub 2024 Oct 11.

Abstract

Aim: Immune-checkpoint inhibitors (ICIs) have revolutionized treatment of metastatic head and neck squamous cell carcinomas (HNSCCs). Our goal was to assess for an association between immune-related adverse events (irAEs) and clinical outcomes for patients on ICIs.Methods: We analyzed a cohort of 110 HNSCC patients who received ICI therapy at the University of Virginia.Results: On review, 48% of our patients experienced an irAE with the most common events being hypothyroidism (30%), dermatitis (14%) and hepatitis (11%). Women were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% patients with irAEs. Development of irAEs was associated with superior objective response rate (68 vs. 39%, p = 0.009), with a greater rate of CR (17 vs. 5%) and PR (32 vs. 16%). Twelve patients underwent ICI re-treatment following irAE, with 17% attaining a complete disease response, 25% attaining a partial response, 33% achieving stable disease and 25% experiencing disease progression with ICI resumption.Conclusion: Development of irAE was associated with superior objective response rate, with a greater rate of CR and PR. ICI re-treatment following irAE was feasible in a significant proportion of patients and can be attempted in carefully selected patients, given the dearth of second-line therapies for these patients.

Keywords: head & neck squamous cell carcinoma; immune-checkpoint inhibitor therapy; immune-related adverse events; ipilimumab; nivolumab; pembrolizumab.

Plain language summary

While outcomes for patients who receive immunotherapy for advanced head and neck cancer are greatly improved compared with traditional chemotherapy, a feared complication of this treatment is immune-related side effects. The exact incidence of these side effects is not known in head and neck cancer but are well described in other cancers. In this study, about half of head and neck cancer patients who received immunotherapy developed side effects due to immune over-activation. Women and patients who did not receive radiation were more likely to develop these side effects. Patient who developed immune side effects were more likely to see shrinkage in their tumors, and may have a higher likelihood of longer survival, although the findings were not statistically significant.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Head and Neck Neoplasms* / immunology
  • Head and Neck Neoplasms* / mortality
  • Head and Neck Neoplasms* / therapy
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Male
  • Middle Aged
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck* / immunology
  • Squamous Cell Carcinoma of Head and Neck* / mortality
  • Squamous Cell Carcinoma of Head and Neck* / therapy

Substances

  • Immune Checkpoint Inhibitors