Fotemustine

点击上方蓝字，后续持续分享[领域]高分文献拆解+复刻技巧       大家好！今天分享一篇原发性中枢神经系统淋巴瘤（PCNSL）领域的重磅文献 —— 发表于《Cancer》（IF=5.1，中科院 1 区 TOP 刊），核心结论颠覆认知：用奥布替尼（BTK 抑制剂）+ 信迪利单抗（PD-1 抑制剂）+ 福莫司汀（非甲氨蝶呤化疗）作为 PCNSL 一线治疗，客观缓解率高达 85.2%，且毒性可控，比传统甲氨蝶呤方案更安全耐受。 不管是做血液肿瘤、神经肿瘤的科研人，还是关注肿瘤免疫联合治疗、靶向药物研发的朋友，都能从这篇文章里挖到实用价值 —— 不仅解决了 PCNSL 治疗的毒性痛点，其 “靶向 + 免疫 + 高 BBB 穿透化疗” 的组合思路，还能迁移到脑转移瘤、颅内肿瘤等多个领域。 生信解读员为您解读， 发表高分SCI，生信解读员为您提供专属服务！ 文献核心信息卡 期刊信息 Cancer/IF=5.1 发表时间 2026 年 1 月 研究领域 血液肿瘤（PCNSL）生信 + 临床联合治疗 一句话结论 奥布替尼（BTK 抑制剂）+PD-1 抑制剂 + 福莫司汀的无甲氨蝶呤方案，对 PCNSL 疗效高且毒性可控，脑脊液乳酸 / IL-1β 可预测预后 核心亮点 生信层面：筛选出 2 个预后生物标志物，用 ROC 曲线验证可靠性（AUC=0.78） 临床层面：规避甲氨蝶呤毒性，为不耐受患者提供新方案 方法层面：“靶向 + 免疫 + 化疗” 组合 + 生信验证，流程可直接复刻到其他肿瘤 研究背景 PCNSL 是一种侵袭性强、发生在中枢神经系统（脑、脊髓、眼等）的大 B 细胞淋巴瘤，属于 “免疫豁免区” 肿瘤，治疗难度大。传统一线方案以高剂量甲氨蝶呤为核心，但毒性极强，治疗相关死亡率高达 5.0%-6.8%，且很多患者（尤其是老年或肝肾功能不佳者）无法耐受。       此前研究虽证实 BTK 抑制剂（如奥布替尼）对 PCNSL 有效（可抑制 B 细胞受体通路）、PD-1 抑制剂能激活颅内免疫、福莫司汀（亚硝基脲类化疗药）能穿透血脑屏障（BBB），但三者联合作为一线方案的疗效与安全性，尚未有系统验证。因此该团队开展这项 1/2 期临床试验，填补了 “无甲氨蝶呤高效低毒一线方案” 的空白。 核心研究路线 研究路线 33 名新诊断 PCNSL 患者（最终 27 人完成疗效评估），中位年龄 62 岁，涵盖不同体能状态（ECOG 1-3）和病理亚型（非 GCB 型占 70.4%）。 研究方法 采用 “剂量爬坡（I 期）+ 疗效验证（II 期）” 的单臂设计，核心是 “奥布替尼（BTK 抑制剂）+ 信迪利单抗（PD-1 抑制剂）+ 福莫司汀（化疗）” 三联方案 ——I 期测试奥布替尼 100/150/200mg 三个剂量，确定 150mg 为推荐剂量；II 期按 “奥布替尼 150mg 每日口服 + 信迪利单抗 200mg 第 1 天静注 + 福莫司汀 100mg/m² 第 2 天静注”，每 21 天一个周期，共 6 个周期。 研究路线       筛选患者→I 期剂量探索（确定安全剂量）→II 期固定剂量治疗→每 2 周期评估疗效→缓解后维持治疗（CR 患者续用奥布替尼 3 个月 + PD-1 抑制剂 1 年；PR 患者加全脑放疗） 关键结果解读 1.生存分析图 图中信息：150mg 奥布替尼组中位 PFS=9.4 个月，显著优于 100mg 组（p=0.010） 核心结论：150mg 是最优推荐剂量，剂量依赖性明确 2.ROC 曲线（基于 Figure4 标志物分析） 图中信息：CSF 乳酸 > 2.4mmol/L 时，预测 1 年 OS 的 AUC=0.78 核心结论：CSF 乳酸是可靠的预后标志物，临床可直接检测应用 价值与局限 价值 对科研人：提供了 “靶向 + 免疫 + BBB 穿透化疗” 的联合治疗框架，可迁移到脑转移瘤、胶质母细胞瘤等颅内肿瘤研究 对临床：为不耐受高剂量甲氨蝶呤的患者（如老年、肝肾功能不全）提供了新一线选择，降低治疗风险 对行业：发现脑脊液（CSF）乳酸升高、IL-1β<7.34pg/mL 可预测更好预后，为 PCNSL 生物标志物研究提供新方向 局限 单臂研究，样本量较小（27 人可评估），需大样本对照试验验证 受新冠疫情影响，多数患者未完成巩固治疗（如全脑放疗、自体干细胞移植），可能影响长期生存数据 未纳入 PD-L1 表达、肿瘤突变负荷（TMB）等更多免疫标志物分析，机制探索可进一步深化 实用复刻指南 这篇文章的临床试验设计和联合用药思路，特别适合肿瘤领域新手复刻，核心步骤拆解如下： 选对药物组合：聚焦 “靶点匹配 + BBB 穿透” 优先选择 “针对肿瘤核心通路的靶向药 + 免疫检查点抑制剂 + 能穿透病变部位屏障的化疗药”—— 比如颅内肿瘤优先选福莫司汀、卡莫司汀等 BBB 穿透性强的化疗药；B 细胞淋巴瘤锁定 BTK 抑制剂（奥布替尼、伊布替尼）。研究设计：从剂量爬坡到 II 期验证的极简流程 采用 “3+3 剂量爬坡（I 期）+ 固定剂量扩展（II 期）”，既保证安全性（确定剂量限制性毒性），又能快速验证疗效；疗效评估按领域权威标准（如 PCNSL 用 IPCG 标准），结合影像学（MRI）+ 体液（CSF 细胞学）+ 局部检查（眼科评估），提高结果可信度。数据收集与分析：重点抓 “疗效 + 安全性 + 标志物” 疗效指标：必收客观缓解率（ORR）、完全缓解率（CR）、无进展生存期（PFS）、总生存期（OS），用 Kaplan-Meier 法做生存分析 安全性：按 NCI-CTCAE 5.0 分级记录不良反应，重点关注 3-4 级毒性及停药率 标志物探索：收集血液 / 脑脊液样本，检测细胞因子（如 IL-1β、乳酸）或基因突变（如 MYD88），用 ROC 曲线确定 cutoff 值，关联生存结局 互动提问 你觉得这篇文章的 “BTK+PD-1 + 化疗” 组合，能应用到哪些其他肿瘤的治疗研究中？ 关注本号，后续持续分享[领域]高分文献拆解+复刻技巧 生信解读员，与您共同分析生信！ 助力大家少走弯路、快速发刊！ 点我私信，立即来料！

BEIJING, Dec. 09, 2025 (GLOBE NEWSWIRE) -- InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company focusing on the treatment of cancer and autoimmune diseases, announced today that over 20 studies of its novel BTK inhibitor orelabrutinib were presented at the 67th Annual Meeting of the American Society of Hematology (ASH). Orelabrutinib has demonstrated remarkable efficacy and safety in multiple lymphoma studies, including marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), primary central nervous system lymphoma (PCNSL), and diffuse large B-cell lymphoma (DLBCL). Oral Presentation Mid-treatment CSF ctdna and MYD88 clearance outperform PET-CT in predicting response and survival to orelabrutinib-based induction in newly diagnosed PCNSL: A prospective biomarker study (Publication No.: 59) The orelabrutinib, rituximab, and high-dose methotrexate (ORM) induction is effective and well tolerated in newly diagnosed PCNSL. Early cerebrospinal fluid (CSF) ctDNA and MYD88 clearance at mid-treatment offer superior predictive and prognostic value compared to PET-CT. These molecular biomarkers enable real-time risk stratification and may guide early treatment adaptation. Incorporating CSF ctDNA monitoring into clinical workflows has the potential to improve response prediction and long-term outcomes in PCNSL. Post-cycle 6, objective response rate (ORR) was 89.5%, with 78.9% complete response rate (CR). Median time to response was 2.6 months; 2-year duration of response (DoR) 72.4%. Median follow-up was 18.9 months; estimated 2-year progression-free survival (PFS) and overall survival (OS) were 62.5% and 75.2%, respectively. Treatment was generally well tolerated. Poster 1. Preliminary analysis of orelabrutinib combined with obinutuzumab in the treatment of marginal zone lymphoma (Orion Study) (Publication No.: 5379) Orelabrutinib combined with obinutuzumab demonstrated promising antitumor activity in treatment-naïve MZL with no severe toxicities observed. These early results support orelabrutinib combined with obinutuzumab regimen as a potential chemotherapy-free first-line option for MZL. Among 27 efficacy-evaluable patients: 25 patients completed interim assessment: ORR 96.0%, CR rate 72.0%; 10 patients completed 6 cycles assessment: ORR 100%, CR rate 70.0%. 2. Preliminary study results of orelabrutinib in combination with rituximab for treatment-Naïve marginal zone lymphoma: A prospective single-arm clinical trial (Publication No.: 3580) Orelabrutinib combined with rituximab demonstrates promising preliminary efficacy in treatment-naïve MZL patients who failed or were unsuitable for local therapy, with an ORR of 81.8% and a CRR of 72.7%. Despite current limitations of small sample size and short median follow-up, the orelabrutinib in combination with rituximab regimen represents a promising chemotherapy-free option for these patients. 3. Orelabrutinib plus bendamustine-rituximab (OBR) versus bendamustine-rituximab (BR) in transplant-ineligible, intermediate- to high-risk Mantle Cell Lymphoma (MCL) (Publication No.: 3599) The orelabrutinib plus bendamustine-rituximab regimen demonstrated a promising tumor response and favorable survival outcomes compared to the bendamustine-rituximab regimen. These findings suggest that the OBR regimen may serve as a promising treatment option for patients with transplant-ineligible, intermediate- to high-risk MCL. 4. Practice pattern and outcomes in DLBCL by Genetic Subtypes: Preliminary results from a large-scale real-world study in China (Publication No.: 3689) This large-scale real-world study provides treatment patterns and outcomes across DLBCL genetic subtypes in China. Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) plus BTKi demonstrated enhanced efficacy in MCD-like patients, supporting subtype-directed therapy. Updated survival and safety data will be presented. R-CHOP plus orelabrutinib achieved a CR rate of 81.4% in MCD-like subgroup. 5. Pomalidomide, rituximab, and orelabrutinib in combination with polatuzumab vedotin for newly diagnosed diffuse large B-cell lymphoma in elderly, unfit, or frail patients: a prospective phase II study (Publication No.: 1912) The preliminary results suggest that the PRO-Pola regimen is a potential treatment option for elderly, unfit, or frail patients with DLBCL, exhibiting promising efficacy and an acceptable safety profile - particularly in those who responded to PRO induction therapy. Among the patients completed ≥3 cycles of treatment, CRR and ORR reached 77.8% and 100.0% respectively. Among the patients who completed all 6 cycles of treatment, both the CRR and ORR reached 100.0%. Publication Only: Efficacy and safety of orelabrutinib monotherapy in patients with chronic lymphocytic leukemia: A retrospective real-world study (Abstract ID: abs25-8605) This real-world study suggested that orelabrutinib monotherapy showed promising efficacy and a favorable safety profile in patients with CLL, both as first-line and subsequent therapy. Patients receiving first-line orelabrutinib achieved both an ORR and DCR of 100%. More studies on orelabrutinib have been selected for poster presentation and publication only at the 2025 ASH Annual Meeting. The other studies selected for poster presentation are as follows: Efficacy and safety of orelabrutinib, obinutuzumab, and lenalidomide in previously untreated marginal zone lymphoma: Preliminary results from a prospective, single-arm, multicenter, Phase II study (Publication No.: 5383)Orelabrutinib combined with bendamustine-rituximab or obinutuzumab followed by orelabrutinib maintenance in untreated marginal zone lymphoma (Optimize): A multicenter, single-arm, phase II study (Publication No.: 3596)Real-world efficacy and safety of orelabrutinib-based regimens in the treatment of marginal zone lymphoma (Publication No.: 1817)Single-cell transcriptomic profiling reveals tumor-intrinsic heterogeneity and immunemicro environment dynamics in the order trial for mantle-cell lymphoma (Publication No.: 1792)Orelabrutinib combined with R-CDOP regimen for first-line treatment of diffuse large Bcell lymphoma with high-risk CNS-IPI (Publication No.: 5460)Preliminary result of first-line orelabrutinib plus R-CHOP in CD5-positive diffuse large B-cell lymphoma (Rocket trial): A single-arm, phase II trial (Publication No.: 3690)Exploration of optimal high-dose methotrexate-based therapy for patients with primary CNS lymphoma: A real-world study in China (Publication No.: 3693)Chemotherapy-free induction with pomalidomide, orelabrutinib, and rituximab (POR) followed by high-dose methotrexate,rituximab and orelabrutinin (ROM) in newly diagnosed primary CNS lymphoma: Interim analysis of a phase II study (Publication No.: 5471)Orelabrutinib plus anti-PD-1 antibody and fotemustine for newly diagnosed primary central nervous system lymphoma: Phase I/II results (Publication No.: 5465)Orelabrutinib, rituximab, and thiotepa (ORT) in combination with or without high-dose methotrexate in untreated primary central nervous system lymphoma (Publication No.: 1911)Primary efficacy and safety of first-line R-MTO regimen (rituximab, methotrexate, thiotepa, and orelabrutinib) followed by autologous hematopoietic stem cell transplantation in PCNSL (Publication No.: 3687)Orelabrutinib, sintilimab, and temozolomide (OST) in relapsed/refractory primary central nervous system lymphoma (Publication No.: 5461) About InnoCare InnoCare is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancers and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and the United States. InnoCare Forward-looking Statements This report contains the disclosure of some forward-looking statements. Except for statements of facts, all other statements can be regarded as forward-looking statements, that is, about our or our management's intentions, plans, beliefs, or expectations that will or may occur in the future. Such statements are assumptions and estimates made by our management based on its experience and knowledge of historical trends, current conditions, expected future development and other related factors. This forward-looking statement does not guarantee future performance, and actual results, development and business decisions may not match the expectations of the forward-looking statement. Our forward-looking statements are also subject to a large number of risks and uncertainties, which may affect our short-term and long-term performance. Contact Media InvestorsChunhua Lu 86-10-66609879 86-10-66609999chunhua.lu@innocarepharma.com ir@innocarepharma.com