Efficacy of PD-1 inhibitor plus induction chemotherapy for nasopharyngeal carcinoma with high-grade extranodal extension: a multicenter retrospective analysis.

BACKGROUNDS: High-grade radiologic extranodal extension (G2/3-rENE) is a well-established adverse prognostic factor in nasopharyngeal carcinoma (NPC), as demonstrated in our previous research. This study aims to evaluate the efficacy and safety of combining a PD-1 inhibitor with induction chemotherapy (IC) in this high-risk patient population. METHODS: We retrospectively analyzed 217 histologically confirmed non-metastatic NPC patients from three centers. Group A (n = 104) received IC plus anti-PD-1 therapy followed by concurrent chemoradiotherapy (CCRT), while Group B (n = 113) received IC alone followed by CCRT. Clinical response rates, survival outcomes, and treatment-related toxicities were compared, and subgroup analyses were performed. RESULTS: Post-IC, Group A demonstrated superior clinical outcomes compared to Group B, with a significantly higher complete response rate (CRR: 21.15% vs. 7.96%, p = 0.001) and objective response rate (ORR: 97.12% vs. 88.50%, p = 0.001). Furthermore, the combination group showed markedly improved rates of 2-year progression-free survival (PFS: 93.2% vs. 81.0%) and distant metastasis-free survival (DMFS: 97.1% vs. 84.8%). Subgroup analyses revealed that patients with baseline EBV DNA < 400 IU/mL, LDH < 2×ULN, T3–4 or N2-3 stage, stage IVa disease, and G3-rENE benefited more from combined treatment. Post-treatment immune profiling revealed reduced total lymphocyte counts with decreased CD4⁺and increased CD8⁺T cells, resulting in a lower CD4⁺/CD8⁺ratio. Morover, patients exhibiting a less pronounced decrease in this ratio were more likely to achieve a complete response. CONCLUSIONS: PD-1 blockade with IC significantly improves disease control in high-risk NPC patients with G2/3-rENE. T cell subset dynamics may help predict treatment response, supporting the incorporation of immunotherapy regimens as frontline treatment for this patient population.