Xiao Xi-Bin, Weng Yi-Qin, Jiang Hua-Wei, Li Xian, Xie Jing, Bao Chang-Qian, Qian Wen-Bin
Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Department of Hematology, Yuyao People's Hospital of Zhejiang Province, The Affiliated Yangming Hospital of Ningbo University, Ningbo, China.
Invest New Drugs. 2025 May 27. doi: 10.1007/s10637-025-01548-1.
Limited treatment options for primary central nervous system lymphoma (PCNSL) highlight the need for alternative therapies. This study evaluated orelabrutinib (O) and rituximab (R), plus high-dose methotrexate (M) (ORM), as a potential induction therapy for newly diagnosed PCNSL.
Patients received six cycles of 150 mg/day orelabrutinib, 375 mg/m rituximab, plus 3.5 g/m methotrexate every 3 weeks, followed by autologous hematopoietic stem cell transplantation and orelabrutinib maintenance. The primary endpoint was the overall response rate (ORR) at the end of induction therapy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
From October 21, 2020, to October 22, 2024, 28 patients were treated and evaluated for efficacy and safety analyses. At the end of induction therapy, the ORR was 71.4% (95% CI, 51.3-86.8), including 16 (57.1%) complete and 4 (14.3%) partial responses. At a median follow-up of 21.6 months, the median PFS was 35.3 months (95% CI, 8.4-not evaluable), and the median OS was not reached, with PFS and OS rates of 64.3% and 96.3% at 1 year, 64.3% and 90.9% at 2 years, and 45.9% and 82.7% at 3 years, respectively. All 28 (100%) patients experienced treatment-related adverse events (TRAEs) of any grade. Grade 3 TRAEs occurred in seven (25.0%) patients, including five (17.9%) leukopenia, one (3.6%) thrombocytopenia, and one (3.6%) diarrhea. No other Bruton's tyrosine kinase inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) or TRAE-related deaths were observed.
The ORM induction regimen showed anti-tumor activity with a favorable safety profile, offering a potential therapeutic strategy for newly diagnosed PCNSL.
ClinicalTrials.gov: NCT05600660.
原发性中枢神经系统淋巴瘤（PCNSL）的治疗选择有限，这凸显了对替代疗法的需求。本研究评估了奥雷巴替尼（O）、利妥昔单抗（R）联合大剂量甲氨蝶呤（M）（ORM）作为新诊断PCNSL的潜在诱导治疗方案。
患者接受六个周期的治疗，其中奥雷巴替尼每日150毫克、利妥昔单抗375毫克/平方米，每3周联合3.5克/平方米甲氨蝶呤，随后进行自体造血干细胞移植及奥雷巴替尼维持治疗。主要终点为诱导治疗结束时的总缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）和安全性。
从2020年10月21日至2024年10月22日，28例患者接受治疗并进行疗效和安全性分析。诱导治疗结束时，ORR为71.4%（95%CI，51.3 - 86.8），包括16例（57.1%）完全缓解和4例（14.3%）部分缓解。中位随访21.6个月时，中位PFS为35.3个月（95%CI，8.4 - 不可评估），中位OS未达到，1年时PFS和OS率分别为64.3%和96.3%，2年时分别为64.3%和90.9%，3年时分别为45.9%和82.7%。所有28例（100%）患者均经历了任何级别的治疗相关不良事件（TRAEs）。3级TRAEs发生在7例（25.0%）患者中，包括5例（17.9%）白细胞减少、1例（3.6%）血小板减少和1例（3.6%）腹泻。未观察到其他布鲁顿酪氨酸激酶抑制剂相关的脱靶毒性（如房颤/房扑）或TRAEs相关死亡。
ORM诱导方案显示出抗肿瘤活性且安全性良好，为新诊断的PCNSL提供了一种潜在的治疗策略。
ClinicalTrials.gov：NCT05600660。
