Abstract：
Metastatic urothelial carcinoma (mUC) is associated with poor prognosis. Cisplatin-based combination chemotherapy is the preferred initial regimen for patients with mUC. However, a substantial proportion of patients cannot receive cisplatin-based chemotherapy due to renal impairment or other comorbidities. Currently, immune checkpoint inhibitors (ICI) showed to be effective in cisplatin-ineligible mUC patients on first-line treatment. Tislelizumab is an anti-human programmed death receptor-1 monoclonal IgG4 antibody, which was specifically engineered to minimize binding to FcɣR on macrophages to abrogate antibody-dependent phagocytosis. But there is no report of tislelizumab as a first-line treatment for cisplatin-ineligible patients with mUC currently. Here, we report a cisplatin-ineligible mUC patient with PD-L1-negative, microsatellite stable (MSS), high tumor mutational burden (TMB-H) obtained complete response receiving tislelizumab therapy after laparoscopic debulking surgery. Progression-free survival has exceeded 16 months since treatment with tislelizumab. To our knowledge, this is the first reported case of cisplatin-ineligible mUC patient with PD-L1-negative, MSS and TMB-H who responded well to tislelizumab as a first-line treatment. However, we still need more studies to assess the efficacy of tislelizumab as a first-line treatment in cisplatin-ineligible mUC patients and to confirm predictive values of TMB for efficacy of tislelizumab.
摘要：
转移性尿路上皮癌（mUC）与不良预后相关。基于顺铂的联合化疗是mUC患者的首选初始方案。然而,相当比例的患者由于肾损害或其他合并症而不能接受以顺铂为基础的化疗.目前,免疫检查点抑制剂(ICI)在一线治疗的顺铂不合格mUC患者中显示有效.Tislelizumab是一种抗人程序性死亡受体-1单克隆IgG4抗体，它经过专门设计以最大程度地减少与巨噬细胞上的FcγR的结合，以消除抗体依赖性吞噬作用。但目前尚无tislelizumab作为顺铂不合格mUC患者的一线治疗方法的报道。这里,我们报告了一名PD-L1阴性的顺铂不合格mUC患者，微卫星稳定（MSS），高肿瘤突变负荷(TMB-H)在腹腔镜减积手术后接受tislelizumab治疗获得完全缓解.自使用tislelizumab治疗以来，无进展生存期已超过16个月。据我们所知,这是首例PD-L1阴性的顺铂不合格MUC患者，MSS和TMB-H对tislelizumab作为一线治疗反应良好。然而,我们仍需要更多的研究来评估tislelizumab作为一线治疗在顺铂不合格mUC患者中的疗效,并确认TMB对tislizumab疗效的预测值.
