Ferritin as a diagnostic, differential diagnostic, and prognostic marker for immune-related adverse events

Objective: Distinguishing immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) from the AEs caused by chemotherapy, targeted therapy, or infection is highly difficult. This study offers new insights into evaluating the diagnosis, differential diagnostic, and prognostic value of ferritin for irAEs induced by ICIs. Methods: From December 1, 2018, to April 1, 2019, we examined 318 patients with malignant tumors who received serum ferritin monitoring. The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy, and 87 patients treated with chemotherapy. Of the 231 patients, 90 had irAEs (irAE group), 70 had non-irAEs (non-irAE group), 67 had no AEs (no irAE-non irAE group), and 4 had unclassified AEs. In the 87 patients, 60 had AEs (AE group), and 27 had no AEs (no AE group). Statistical analyses were conducted with nonparametric Mann-Whitney tests. Results: At the onset of AEs in the irAE group, ferritin (normal range, 35-150 mu g/L) rose to a median of 927 mu g/L (range, 117-17,825 mu g/L) from 86 mu g/L at baseline (range, 29-421 mu g/L) (P < 0.001). Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group (median, 81 mu g/L; range, 32-478 mu g/L) (P < 0.001) and the AE group (median, 103 mu g/L; range, 23-712 mu g/L) (P < 0.001). After treatment in the irAE group, ferritin continuously decreased to a normal range in recovered patients, showed no significant changes in stable patients, and continued to rise in patients who died. Conclusions: Ferritin can be used as a diagnostic, differential diagnostic, and prognostic marker for irAEs in patients treated with ICIs.