Camrelizumab Plus Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin in Relapsed/Refractory Primary Mediastinal B-Cell Lymphoma: A Single-Arm, Open-Label, Phase II Trial
Camrelizumab Plus Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin in Relapsed/Refractory Primary Mediastinal B-Cell Lymphoma: A Single-Arm, Open-Label, Phase II Trial
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Camrelizumab 加吉西他滨、长春瑞滨和聚乙二醇化脂质体阿霉素治疗复发/难治性原发性纵隔 B 细胞淋巴瘤：一项单组、开放标签、II 期试验。
DOI：
10.1158/1078-0432.ccr-20-0514
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发表时间：
2020-09-01
影响因子：
11.5
通讯作者：
Han, Weidong
中科院分区：
文献类型：
--
作者：
Mei, Qian;Zhang, Wenying;Han, Weidong
目的：复发/难治性原发性纵隔b细胞淋巴瘤（rrPMBCL）患者是一个特别具有挑战性的治疗人群，在预后不理想的情况下，几乎没有挽救生命的治疗选择。患者和方法：在这项开放标签、单组、II期研究中，评估了由吉西他滨、长春瑞滨和聚乙二醇化脂质体阿霉素（GVD）加抗pd -1抗体camrelizumab组成的联合化疗方案在rrPMBCL中的安全性和有效性。患者每3周接受一次化学免疫治疗，直到第二次确认完全缓解（CR）或最多12个周期，随后进行camrelizumab单药治疗长达1年。主要终点为客观缓解率（ORR）和安全性。结果：27例反应可评估的患者入组，他们接受了3种一线治疗的中位数，59%的患者患有大体积疾病。ORR为74%，其中CR为56%。观察到反应的中位时间为1.7个月，78%的患者在第一次评估时显示肿瘤缩小。中位随访24.8个月后，中位缓解持续时间未达到，2年估计缓解率为65%。13名应答者持续完全缓解。估计24个月无进展生存率和总生存率分别为48.2%和81.5%。93%和33%的患者分别发生了任何级别和3级治疗相关不良事件（AE）；没有4级或5级ae。IL10、IFN γ和可溶性Fas的基线水平与客观反应相关。结论：Camrelizumab联合GVD化疗为rrPMBCL患者提供了一个强有力的选择，作为挽救生命的化学免疫治疗，具有良好的疗效和可管理的安全性，特别是对于大体积侵袭性疾病。
Purpose: Patients with relapsed/refractory primary mediastinal B-cell lymphoma (rrPMBCL) represent a particularly challenging population to treat, with few life-saving treatment options in the context of a dismal prognosis.Patients and Methods: In this open-label, single-arm, phase II study, the safety and efficacy of combined regimen of chemotherapy consisting of gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) plus anti-PD-1 antibody camrelizumab was assessed in rrPMBCL. Patients received chemo-immunotherapy every 3 weeks until the second confirmed complete response (CR) or up to 12 cycles, followed by camrelizumab monotherapy for up to 1 year. The primary endpoints were objective response rate (ORR) and safety.Results: Twenty-seven response evaluable patients were enrolled, who received a median of three first-line therapies, 59% with bulky disease. The ORR was 74%, including 56% with a CR. A median time of 1.7 months to response was observed, with 78% exhibiting tumor shrinkage at the first evaluation. After 24.8 months median follow-up, the median duration of response was not reached, with a 65% 2-year estimated response rate. Thirteen responders remained in sustained complete remission. Estimated 24-month progression-free survival and overall survival rates were 48.2% and 81.5%, respectively. Any grade and grade 3 treatment-related adverse events (AE) occurred in 93% and 33% of patients, respectively; with no grade 4 or 5 AEs. Baseline levels of IL10, IFN gamma, and soluble Fas were associated with objective response.Conclusions: Camrelizumab plus GVD chemotherapy offers a potent option as life-saving chemo-immunotherapy with promising efficacy and a manageable safety profile for patients with rrPMBCL, especially with bulky aggressive disease.