Wang Wenhua, Wang Bingyi, Sun Yifei, Qiu Lihua, Qian Zhengzi, Zhou Shiyong, Song Zheng, Li Wei, Li Lanfang, Wang Xianhuo, Zhang Huilai
State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, The Sino-United States Center for Lymphoma and Leukemia Research, Tianjin, China.
Front Immunol. 2025 May 22;16:1579483. doi: 10.3389/fimmu.2025.1579483. eCollection 2025.
This study aimed to evaluate the efficacy and safety of rituximab, methotrexate, cytarabine with or without ibrutinib in newly diagnosed primary central nervous system lymphoma (PCNSL) and explore the correlation between efficacy and genomic alterations.
From March 2013 to October 2022, data from 88 patients with newly diagnosed PCNSL were retrospectively collected and analyzed. Fifty-nine patients received rituximab, methotrexate and cytarabine (RMA, group A), and twenty-nine patients received the same RMA combined with ibrutinib (RMA + Ibrutinib, group B).
At a median follow-up of 27.7 months, the complete response rate (CRR), overall response rate (ORR) and overall survival (OS) in group B superior to group A (41.4% versus 16.9% for CRR, P=0.013; 86.2% versus 59.3% for ORR, =0.011; P=0.036 for OS). The ORR, progression-free survival (PFS) and OS of RMA + ibrutinib +deep lesions (group C) were better than those of RMA + deep lesions (group D) (=0.027 for ORR, 0.046 for PFS, =0.004 for OS). Patients in group B had no more toxicities than those in group A and the most common adverse events in the two groups were primarily grade 1-2. Sequencing of tumor tissues from 22 patients showed that mutations were the most frequent genetic alterations, two patients with mutation did not respond to treatment and three patients without an or had response after treatment.
RMA in combination with ibrutinib regimen improved response rates and survival in newly diagnosed PCNSL with no serious adverse effects. Mutations in gene may provide directions for patients to select targeted drugs.
本研究旨在评估利妥昔单抗、甲氨蝶呤、阿糖胞苷联合或不联合伊布替尼治疗新诊断的原发性中枢神经系统淋巴瘤(PCNSL)的疗效和安全性,并探讨疗效与基因组改变之间的相关性。
回顾性收集并分析2013年3月至2022年10月期间88例新诊断PCNSL患者的数据。59例患者接受利妥昔单抗、甲氨蝶呤和阿糖胞苷(RMA,A组),29例患者接受相同的RMA联合伊布替尼(RMA + 伊布替尼,B组)。
中位随访27.7个月时,B组的完全缓解率(CRR)、总缓解率(ORR)和总生存期(OS)均优于A组(CRR分别为41.4%和16.9%,P = 0.013;ORR分别为86.2%和59.3%,P = 0.011;OS,P = 0.036)。RMA + 伊布替尼 + 深部病变组(C组)的ORR(P = 0.027)、无进展生存期(PFS,P = 0.046)和OS(P = 0.004)均优于RMA + 深部病变组(D组)。B组患者的毒性反应并不比A组多,两组最常见的不良事件主要为1-2级。对22例患者的肿瘤组织进行测序显示,突变是最常见的基因改变,2例有突变的患者对治疗无反应,3例无或无突变的患者治疗后有反应。
RMA联合伊布替尼方案提高了新诊断PCNSL的缓解率和生存率,且无严重不良反应。基因的突变可能为患者选择靶向药物提供指导。