Abstract A143: Toxicity profile of immune checkpoint inhibitors in locoregionally advanced nasopharyngeal carcinoma: A meta-analysis of general and hematologic adverse events from phase II and III randomized trials

Abstract Background: Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy in the management of locoregionally advanced nasopharyngeal carcinoma (LA-NPC), particularly when integrated with established chemoradiotherapy regimens. While randomized trials have demonstrated encouraging oncologic outcomes, the toxicity profile of these agents remains incompletely defined. Hematologic adverse events such as leukopenia are of concern given their potential to compromise treatment delivery. This meta-analysis synthesizes data from recent phase II and III randomized controlled trials to characterize the incidence of leukopenia and other treatment-related toxicities associated with ICI-based therapy in LA-NPC. Methods: A comprehensive literature search was conducted using MEDLINE and EMBASE through July 10, 2025. Randomized controlled trials (RCTs) utilizing ICIs in LA-NPC and reporting general and hematologic adverse events were included. The Mantel-Haenszel method was used to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s Q-statistic. A fixed-effects model was applied. Results: A total of 1,016 patients from two phase III randomized controlled trials (CONTINUUM: n=508; DIPPER: n=278) and one phase II randomized controlled trial (Liu Se et al., 2024: n=230) were included in this meta-analysis. All three trials evaluated the use of ICIs in the treatment of locoregionally advanced nasopharyngeal carcinoma. The phase III CONTINUUM trial investigated the addition of sintilimab to standard therapy. Patients were randomized 1:1 to receive induction gemcitabine and cisplatin followed by concurrent chemoradiotherapy, with or without sintilimab administered during induction, concurrent, and adjuvant phases. The phase III DIPPER trial evaluated the use of adjuvant camrelizumab. Patients who had completed induction chemotherapy and concurrent chemoradiotherapy were randomized 1:1 to receive either adjuvant camrelizumab or observation. The phase II trial examined neoadjuvant and adjuvant toripalimab. Patients were randomized in a 2:1 ratio to receive neoadjuvant toripalimab or placebo prior to chemoradiotherapy, followed by adjuvant toripalimab or placebo. Across the pooled analysis, any-grade leukopenia occurred in 65.3% of patients receiving ICI therapy compared to 56.5% in the control group (RR 1.09; 95% CI: 1.01–1.18; p=0.04). High-grade leukopenia occurred in 20.3% versus 20.8%, respectively (RR 0.79; 95% CI: 0.64–0.97; p=0.02). No statistically significant differences were observed between groups in the incidence of any-grade or high-grade nausea, vomiting, weight loss, or anemia. Conclusion: ICI-based therapy in locoregionally advanced nasopharyngeal carcinoma is associated with a modest increase in any-grade leukopenia but not high-grade events. No significant differences were observed in gastrointestinal or constitutional toxicities. These findings support the tolerability of ICIs when integrated into standard treatment regimens. Citation Format: Jason Ta, Ramaditya Srinivasmurthy, Daniel T. Jones, Taimur Khalid, Riccesha Hattin, Abbas Hussain, Kenny Do, Rishi K. Nanda, Yin M. Myat, Sisi Tian, Jo-Lawrence Bigcas, Kyaw Z. Thein. Toxicity profile of immune checkpoint inhibitors in locoregionally advanced nasopharyngeal carcinoma: A meta-analysis of general and hematologic adverse events from phase II and III randomized trials [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr A143.