Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy. Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle. Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell’s syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively. Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing. NCT04446962.

中文翻译：

---

LOC-R01 的 IB 期部分，一项 LOC 网络非比较随机 IB/II 期研究，测试 R-MPV 联合递增剂量的来那度胺或依鲁替尼治疗新诊断的原发性中枢神经系统淋巴瘤 （PCNSL） 患者


原发性中枢神经系统淋巴瘤 （PCNSL） 的常规诱导化疗的结果需要改进。BTK 抑制剂伊布替尼和免疫调节药物来那度胺在复发时显示出有希望的结果，支持进一步评估它们与基于甲氨蝶呤的大剂量化疗联合使用的个体使用情况。新诊断的 PCNSL 患者被随机分配接受四个 28 天周期的依鲁替尼或来那度胺联合 R-MPV （利妥昔单抗、甲氨蝶呤、丙卡巴肼、长春新碱和泼尼松） 在 3 + 3 设计中。然后，反应者接受 R-阿糖胞苷巩固治疗和自体干细胞移植强化化疗。IB 期研究的目的是根据第一个诱导周期期间发生的剂量限制性毒性 （DLT） 确定推荐的 II 期剂量 （RP2D）。26 例患者 （中位年龄 52） 被随机分组。观察到 4 例 DLT： 1 例 5 级曲霉病和肺孢子菌病，1 例 4 级导管相关感染和 2 例 3 级丙氨酸氨基转移酶水平升高。依鲁替尼和来那度胺与 R-MPV 联合使用的 RP2D 分别为每天 560 mg （D3-14 和 D17-28） 和 15 mg 每天 （D1-21）。在两组中，最常见的 ≥3 级治疗相关不良事件是肝细胞溶解、中性粒细胞减少和感染。在第 2 周期，来那度胺组报告了 1 例 4 级 Lyell 综合征。4 个诱导周期后，来那度胺组和依鲁替尼组的总体缓解率分别为 76.9% 和 83.3%。来那度胺或依鲁替尼与 R-MPV 联合的靶向诱导治疗对于一线 PCNSL 是可行的。安全性与 R-MPV 和两种靶向治疗的已知安全性一致。 该研究的 II 期部分正在进行中。NCT04446962。