The clinical potential of HMGB1 for the risk assessment of severe checkpoint inhibitor pneumonitis: A prospective multicenter study (CS-Lung004).

BACKGROUND

Checkpoint inhibitor pneumonitis (CIP), especially graded as 3-5 or developed within 6-12 weeks, worsens the prognosis of patients with cancer. However, a risk assessment method for the disease has not been established. This was a prospective study that aimed to identify a blood biomarker to assess a risk of severe CIP.

PATIENTS AND METHODS

This multicenter prospective study enrolled patients with non-small cell lung cancer who were treated with anti-PD-1/PD-L1 antibodies in the first-line therapy. The potential of high mobility group box 1 (HMGB1) for Grade 3-5 CIP developed within 3 months after the first administration of anti-PD-1/PD-L1 antibody (CIP/3months) was evaluated in the discovery cohort (December 2021-November 2022) and validation cohort (December 2022-November 2023).

RESULTS

In the discovery and validation cohorts, 8.2 % and 6.2 % of patients experienced CIP/3months, respectively. The HMGB1 cut-off level was set at 8.1 ng/mL by receiver operating characteristic analysis in the discovery cohort (AUC = 0.732), yielding 80.0 % sensitivity and 71.1 % specificity in the validation cohort. The incidence rate of CIP/3months was significantly higher in patients with high HMGB1 level than in those without, both in the discovery cohort (18.2 % and 2.6 %, respectively; P = 0.028) and validation cohort (15.4 % and 1.8 %, respectively; P = 0.035). The potential of HMGB1 for assessing the risk was specific for CIP because HMGB1 serum levels were not elevated in patients with immune related adverse events other than CIP.

CONCLUSION

HMGB1 can be a serum biomarker that specifically assesses the risk of severe CIP.