Immune checkpoint inhibitors (ICIs) show limited clinical activity in patients with advanced soft-tissue sarcomas (STSs). Retrospective analysis suggests that intratumoral tertiary lymphoid structures (TLSs) are associated with improved outcome in these patients. PEMBROSARC is a multicohort phase 2 study of pembrolizumab combined with low-dose cyclophosphamide in patients with advanced STS (NCT02406781). The primary endpoint was the 6-month non-progression rate (NPR). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety. The 6-month NPR and ORRs for cohorts in this trial enrolling all comers were previously reported; here, we report the results of a cohort enrolling patients selected based on the presence of TLSs (n = 30). The 6-month NPR was 40% (95% confidence interval (CI), 22.7–59.4), so the primary endpoint was met. The ORR was 30% (95% CI, 14.7–49.4). In comparison, the 6-month NPR and ORR were 4.9% (95% CI, 0.6–16.5) and 2.4% (95% CI, 0.1–12.9), respectively, in the all-comer cohorts. The most frequent toxicities were grade 1 or 2 fatigue, nausea, dysthyroidism, diarrhea and anemia. Exploratory analyses revealed that the abundance of intratumoral plasma cells (PCs) was significantly associated with improved outcome. These results suggest that TLS presence in advanced STS is a potential predictive biomarker to improve patients’ selection for pembrolizumab treatment.

免疫检查点抑制剂 (ICI) 在晚期软组织肉瘤 (STS) 患者中的临床活性有限。回顾性分析表明，肿瘤内三级淋巴结构 (TLS) 与这些患者的预后改善有关。PEMBROSARC 是 pembrolizumab 联合低剂量环磷酰胺治疗晚期 STS 患者的多队列 2 期研究 (NCT02406781)。主要终点是 6 个月的无进展率（NPR）。次要终点包括客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和安全性。先前报告了该试验中招募所有参与者的队列的 6 个月 NPR 和 ORR；在这里，我们报告了根据 TLS 的存在选择的队列招募患者的结果（n = 30)。6 个月的 NPR 为 40%（95% 置信区间 (CI)，22.7-59.4），因此达到了主要终点。ORR 为 30% (95% CI, 14.7–49.4)。相比之下，所有参与者的 6 个月 NPR 和 ORR 分别为 4.9%（95% CI，0.6-16.5）和 2.4%（95% CI，0.1-12.9）。最常见的毒性是 1 级或 2 级疲劳、恶心、甲状腺功能障碍、腹泻和贫血。探索性分析表明，肿瘤内浆细胞 (PC) 的丰度与改善结果显着相关。这些结果表明，晚期 STS 中 TLS 的存在是一种潜在的预测性生物标志物，可改善患者对 pembrolizumab 治疗的选择。