Sequential or concurrent immunotherapy with locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma.

Abstract

2622 Background: First-line chemotherapy combined with immunotherapy (CT-IO), followed by selective locoregional radiotherapy (LRRT), has emerged as the mainstay treatment for de novo metastatic nasopharyngeal carcinoma (dmNPC). However, the efficacy of adding concurrent immunotherapy to LRRT remains controversial. Methods: This study enrolled patients with dmNPC who received platinum-based chemotherapy, anti–PD-1 immunotherapy, and definitive LRRT. Survival outcomes were assessed using a 12-month landmark analysis to minimize immortal time bias. Inverse probability of treatment weighting (IPTW) was employed to balance baseline characteristics between the CCRT+IO (LRRT with concurrent immunotherapy) and CCRT-IO (LRRT without concurrent immunotherapy) groups. Recursive partitioning analysis (RPA) utilizing baseline and post-CT-IO factors was applied to stratify patients into low- or high-risk groups to evaluate the benefit of concurrent IO. Absolute lymphocyte count (ALC) was monitored during and up to 6 months post-LRRT. Results: A total of 238 patients were included (185 receiving concurrent IO and 53 without). In the IPTW-adjusted Kaplan-Meier analysis at the 12-month landmark, the addition of concurrent IO was associated with significantly inferior progression-free survival (PFS) (Hazard Ratio [HR]: 3.189; 95% CI, 1.352–7.524; p = 0.008). The "Sandwich" mode—comprising 4-6 cycles of induction CT-IO, followed by LRRT, and subsequent IO maintenance—yielded the optimal survival outcomes (HR: 0.288; 95% CI, 0.106–0.786; p = 0.015). An RPA model incorporating five prognostic factors (the number of metastatic lesions, pretreatment LDH level, post-CT-IO Epstein-Barr virus DNA, and radiological response post-CT-IO) stratified patients into two risk subgroups. Low-risk patients derived no clinical benefit from concurrent IO (p = 0.134), whereas high-risk patients exhibited significantly worse 12-month landmark adjusted PFS (p = 0.031). Notably, subgroup analysis showed that patients with persistent radiation-induced lymphocytopenia at 3 months post-RT demonstrated the most unfavorable survival outcomes after concurrent immunotherapy (p < 0.001). Conclusions: DmNPC patients receiving first-line CT-IO followed by LRRT did not benefit from concurrent immunotherapy during RT, particularly those identified as high-risk by the prognostic model and those with persistent lymphocytopenia at 3 months post-RT.