Comparison of immune-related adverse events and analysis of risk factors in older and younger rectal cancer patients receiving immunotherapy.

BACKGROUND

Immunotherapy has transformed rectal cancer treatment but poses risks of immune-related adverse events (irAEs), particularly in elderly patients who exhibit immunosenescence and inflammaging. This study compares the incidence and severity of irAEs in elderly and young rectal cancer patients receiving immunotherapy and identifies predictive biomarkers for these events.

METHODS

We retrospectively analyzed 405 rectal cancer patients treated with immunotherapy from January 2015 to December 2023. Patients were categorized into younger (< 60 years) and older (≥ 60 years) groups. Incidence and severity of irAEs were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) standards. Blood samples were analyzed for hematological and immunological markers.

RESULTS

The older group displayed a significantly higher incidence of irAEs at 48.65% compared to 32.11% in the younger group ( = 0.003). Severity varied, with 69.72% of younger patients experiencing irAEs of grade ≤ 2 versus 51.69% in the older group ( = 0.001). Notably, higher absolute lymphocyte count (ALC), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were associated with increased irAEs ( = 0.002, = 0.001, = 0.007, respectively). The multivariate analysis identified ALC, IL-6, CRP, B and T Lymphocyte Attenuator, Human Granulocyte-macrophage Colony Stimulating Factor, Programmed Death-1 and Programmed Death-Ligand 1 as significant predictors of irAEs, with ALC showing an odds ratio (OR) of 9.700 ( = 0.001) and IL-6 an OR of 58.961 ( < 0.001). Furthermore, the platelet-to-lymphocyte ratio (PLR) inversely correlated with irAEs ( = 0.013).

CONCLUSION

Older rectal cancer patients receiving immunotherapy were at increased risk for both greater incidence and severity of irAEs. Specific biomarkers, such as ALC and IL-6, were associated with a heightened risk of these events.