辛替利单抗(抗 PD-1 抗体)联合大剂量甲氨蝶呤、替莫唑胺和利妥昔单抗(抗 CD20 抗体)治疗原发性中枢神经系统淋巴瘤:一项 2 期研究。

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zhiyong Zeng, Apeng Yang, Jingke Yang, Sheng Zhang, Zhen Xing, Xingfu Wang, Wenzhong Mei, Changzhen Jiang, Junfang Lin, Xiyue Wu, Yihui Xue, Zanyi Wu, Lianghong Yu, Dengliang Wang, Jianwu Chen, Shufa Zheng, Qiaoxian Lin, Qingjiao Chen, Jinfeng Dong, Xiaoqiang Zheng, Jizhen Wang, Jinlong Huang, Zhenying Chen, Ping Chen, Meihong Zheng, Xiaofang Zhou, Youwen He, Yuanxiang Lin, Junmin Chen
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引用次数: 0

摘要

原发性中枢神经系统淋巴瘤(PCNSL)是一种罕见且经常致命的淋巴瘤亚型。程序性死亡-1(PD-1)通路已成为潜在的治疗靶点,但PD-1抗体sintilimab联合免疫化疗作为PCNSL一线治疗的有效性仍有待确定。在这项具有安全性的 2 期试验(ChiCTR1900027433)中,我们纳入了 18-70 岁的新诊断 PCNSL 患者。参与者接受了 6 个 21 天周期的 SMTR 方案治疗,其中包括辛替利马(200 毫克,第 0 天)、利妥昔单抗(375 毫克/平方米,第 0 天)、甲氨蝶呤(3.0 克/平方米,第 1 天;年龄≥65 岁的患者为 1.0 克/平方米)和替莫唑胺(150 毫克/平方米/天,第 1-5 天)。在27例可评估的患者中,总反应率(ORR)为96.3%(95%置信区间:81-99.9%),其中25例为完全反应。在 24.4 个月的中位随访中,反应持续时间、无进展生存期(PFS)和总生存期的中位数均未达到。最常见的 3-4 级治疗相关毒性是丙氨酸氨基转移酶(17.9%)和天冬氨酸氨基转移酶(14.3%)水平升高。此外,干扰素-α基线水平和脑脊液中的IL10/IL6比值也是预测PFS的潜在指标,2年后的曲线下面积分别为0.88和0.84。全外显子组测序显示,持久临床获益组的RTK-RAS和PI3K通路突变发生率更高,而无持久获益组的Notch和Hippo通路突变发生率更高。这些研究结果表明,SMTR疗法对新诊断的PCNSL疗效显著且可耐受,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study.

Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study.

Primary central nervous system lymphoma (PCNSL) is a rare and frequently fatal lymphoma subtype. The programmed death-1 (PD-1) pathway has emerged as a potential therapeutic target, but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined. In this phase 2 trial (ChiCTR1900027433) with a safety run-in, we included patients aged 18-70 with newly diagnosed PCNSL. Participants underwent six 21-day cycles of a SMTR regimen, which includes sintilimab (200 mg, Day 0), rituximab (375 mg/m2, Day 0), methotrexate (3.0 g/m2, Day 1 or 1.0 g/m2 for patients aged ≥65 years), and temozolomide (150 mg/m2/d, Days 1-5). Among 27 evaluable patients, the overall response rate (ORR) was 96.3% (95% confidence interval: 81-99.9%), with 25 complete responses. At a median follow-up of 24.4 months, the medians for duration of response, progression-free survival (PFS), and overall survival were not reached. The most common grade 3-4 treatment-related toxicities were increased levels of alanine aminotransferase (17.9%) and aspartate aminotransferase (14.3%). Additionally, baseline levels of interferon-α and the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS, achieving areas under the curve of 0.88 and 0.84, respectively, at 2 years. Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group, while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group. These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL, warranting further investigation.

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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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