Association of anti-PD-1 therapy with severe radiation-induced oral mucositis: A retrospective cohort study and validation in the CONTINUUM trial.

Background: The association of immune checkpoint inhibitors (ICIs) with radiation-induced oral mucositis (RIOM), a common and debilitating complication that affects the treatment tolerance of head and neck cancer patients, remains unclear.

Methods: In this multicenter retrospective cohort study, 840 eligible patients with locoregionally advanced nasopharyngeal carcinoma (NPC) were included, with propensity score matching (PSM) creating two comparison groups based on the receipt of anti-programmed cell death 1 (anti-PD-1) therapy. Additionally, individual patient data from 197 NPC patients in the CONTINUUM trial (NCT03700476) were used for validation.

Findings: One-to-one PSM created 215 pairs of patients (ICI group, 215; control group, 215). Although the incidence of severe RIOM was similar between the ICI (n = 92, 42.8%) and control groups (n = 93, 43.3%), multivariable logistic regression revealed that ICI-treated patients with younger age (<45 years), receiving induction chemotherapy (IC) regimens with docetaxel, cisplatin, and 5-fluorouracil/capecitabine (TPF/X) or docetaxel and cisplatin (TP), or with a pre-radiotherapy neutrophil-to-lymphocyte ratio (NLR) ≥2.5 were at an increased risk of severe RIOM. The established nomogram demonstrated excellent performance for predicting severe RIOM risk (concordance index: 0.721 in the ICI group and 0.722 in the CONTINUUM trial).

Conclusions: Anti-PD-1 therapy did not generally increase the incidence of severe RIOM in NPC patients; however, it significantly raised the risk in those under 45 years of age, those receiving TPF/X or TP during IC, or those with a pre-radiotherapy NLR ≥2.5. The established nomogram enables tailored monitoring and intervention strategies for severe RIOM, enhancing management during immunotherapy.

Funding: National Key Research and Development Program of China (2021YFA0909800).