Background: Increasing evidence suggests that the immunogenicity of COVID-19 mRNA vaccines might influence the efficacy of immune checkpoint inhibitors (ICIs). Current studies have not considered the impact of additional vaccinations, which are now recommended as a preventive strategy against SARS-CoV-2 infection for cancer patients receiving active treatments. Consequently, we leveraged the prospective monitoring from the Vax-On-Third study to explore whether periodic mRNA vaccine boosters administered around the start of ICIs could influence the rates of immune-related adverse events (irAEs) and survival outcomes in patients with advanced non-small cell lung cancer (NSCLC). Methods: Our study included patients with a histological diagnosis of metastatic NSCLC and available PD-L1 tumor proportion score (TPS), who had undergone at least two cycles of upfront treatment with pembrolizumab, cemiplimab, or their combination with platinum-based chemotherapy. Patients who received any additional mRNA-based vaccine doses within 60 days before to 30 days after starting ICIs accounted for the exposed cohort. Those who declined further boosters formed the reference cohort. We analyzed differences in irAE frequencies, progression-free survival (PFS), and overall survival (OS) using univariate and multivariate analyses. Results: Between 27 November 2021 and 31 March 2024, we enrolled 226 eligible patients. The exposed cohort consisted of 112 patients who had received either a third or fourth dose of tozinameran or a bivalent booster. Based on PD-L1 expression levels, 93 (41%) and 133 (59%) patients received single-agent ICIs (PD-L1 TPS ≥ 50%) or combination regimens (PD-L1 TPS < 50%), respectively. Propensity-score matching using comprehensive criteria resulted in two cohorts of 102 patients each, with an optimal balance of prognostic factors. A thorough analysis of any grade irAEs showed no significant differences between the cohorts. A longitudinal survival assessment with a median follow-up of 22.8 (95% CI 19.2–26.0) months showed no difference between the cohorts. The median PFS for the reference and exposed cohorts was 7.5 (95% CI 5.9–9.1) and 8.2 (95% CI 6.2–10.2) months, respectively (p= 0.408; HR 0.88 [95% CI 0.66–1.18]). The median OS for the reference and exposed cohorts was 10.5 (95% CI 7.9–13.0) and 13.8 (95% CI 12.0–15.5) months, respectively (p= 0.170; HR 0.81 [95% CI 0.59–1.09]). Multivariate analysis confirmed that receiving additional mRNA vaccine boosters did not significantly affect the risk of disease progression or mortality. Univariate analysis within the subgroup of patients with high PD-L1 TPS who received single-agent ICIs showed a significant OS advantage for patients in the exposed cohort (9.7 [95% CI 8.1–11.2] vs. 18.6 [95% CI 13.5–23.6] months;p= 0.034; HR 0.59 [95% CI 0.36–0.96]). Conclusion: After optimally balancing prognostic factors, regular mRNA vaccine boosters at the onset of ICIs did not impact the safety and survival of patients with advanced NSCLC. The improved outcome observed in patients with high PD-L1 expression levels aligns with previous findings and warrants further investigation.
背景：越来越多的证据表明，COVID-19 mRNA疫苗的免疫原性可能影响免疫检查点抑制剂（ICIs）的疗效。目前的研究尚未考虑额外疫苗接种的影响，而额外接种现已被推荐为接受积极治疗的癌症患者预防SARS-CoV-2感染的策略。因此，我们利用Vax-On-Third研究的前瞻性监测数据，探讨在ICIs治疗开始前后定期接种mRNA疫苗加强针是否会影响晚期非小细胞肺癌（NSCLC）患者的免疫相关不良事件（irAEs）发生率和生存结局。 方法：本研究纳入经组织学诊断为转移性NSCLC且具有PD-L1肿瘤比例评分（TPS）的患者，这些患者至少接受过两个周期的帕博利珠单抗、西米普利单抗或其联合铂类化疗的前线治疗。在开始ICIs治疗前60天至治疗后30天内接受任何额外mRNA疫苗剂量的患者构成暴露队列。拒绝进一步接种加强针的患者构成参照队列。我们采用单变量和多变量分析来评估两组在irAE发生率、无进展生存期（PFS）和总生存期（OS）方面的差异。 结果：2021年11月27日至2024年3月31日期间，我们共纳入226例符合条件的患者。暴露队列包括112例接受了第三剂或第四剂tozinameran或二价加强针的患者。根据PD-L1表达水平，分别有93例（41%）和133例（59%）患者接受了单药ICI治疗（PD-L1 TPS ≥ 50%）或联合方案治疗（PD-L1 TPS < 50%）。通过倾向评分匹配，我们获得了两个各包含102例患者的队列，其预后因素达到最佳平衡。对所有级别irAEs的全面分析显示，两组间无显著差异。中位随访时间为22.8个月（95% CI 19.2–26.0）的纵向生存评估显示，两组间无差异。参照队列和暴露队列的中位PFS分别为7.5个月（95% CI 5.9–9.1）和8.2个月（95% CI 6.2–10.2）（p=0.408；HR 0.88 [95% CI 0.66–1.18]）。参照队列和暴露队列的中位OS分别为10.5个月（95% CI 7.9–13.0）和13.8个月（95% CI 12.0–15.5）（p=0.170；HR 0.81 [95% CI 0.59–1.09]）。多变量分析证实，接受额外mRNA疫苗加强针并未显著影响疾病进展或死亡风险。在PD-L1 TPS高、接受单药ICI治疗的亚组中，单变量分析显示暴露队列患者的OS具有显著优势（9.7个月 [95% CI 8.1–11.2] vs. 18.6个月 [95% CI 13.5–23.6]；p=0.034；HR 0.59 [95% CI 0.36–0.96]）。 结论：在最佳平衡预后因素后，在ICIs治疗开始时定期接种mRNA疫苗加强针并未影响晚期NSCLC患者的安全性和生存期。在PD-L1高表达患者中观察到的改善结局与既往研究结果一致，值得进一步研究。
肿瘤(癌症)患者之家