Maza Sofiane, Kiewe Philipp, Munz Dieter L, Korfel Agnieszka, Hamm Bernd, Jahnke Kristoph, Thiel Eckhard
Department of Hematology, Oncology, and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30/31, 12200 Berlin, Germany.
Neuro Oncol. 2009 Aug;11(4):423-9. doi: 10.1215/15228517-2008-108. Epub 2008 Dec 5.
Most patients with primary CNS lymphoma (PCNSL) relapse after primary therapy. Standard salvage treatment has not yet been established in PCNSL. Anti-CD20 immunotherapy has expanded treatment options in systemic B-cell lymphoma; however, its use is limited by reconstitution of the blood-brain barrier after tumor shrinkage. The aim of this phase II trial was to evaluate the therapeutic efficacy, toxicity, and biodistribution of yttrium-90 ((90)Y) ibritumomab tiuxetan in PCNSL. Ten patients with relapsed PCNSL were included in a phase II trial and treated with the (90)Y-labeled anti-CD20 antibody ibritumomab tiuxetan. Nine patients actually received the planned radioimmunotherapy. In six patients, biodistribution of the antibody was measured by indium-111 ((111)In) ibritumomab tiuxetan whole-body scans and single-photon-emission CT (SPECT) of the brain. All patients were evaluated for toxicity and response at least 4 weeks after therapy. Four patients responded: one patient had a complete response lasting 30+ months, and three patients had short-lived responses of </=4 weeks. Five patients progressed, and one patient did not receive treatment due to an infection prior to (90)Y-antibody administration. Target accumulation of the antibody was demonstrated in four of the six patients examined by SPECT imaging with (111)In ibritumomab tiuxetan. All patients experienced grade 3/4 hematotoxicity but no acute neurotoxicity. Penetration of a therapeutic antibody into PCNSL and significant clinical activity was shown. Because of limited response duration and considerable hematotoxicity, future investigations should focus on a multimodal approach with additional chemotherapy and preferably autologous stem cell support.
大多数原发性中枢神经系统淋巴瘤（PCNSL）患者在初始治疗后会复发。PCNSL的标准挽救治疗方法尚未确立。抗CD20免疫疗法扩大了系统性B细胞淋巴瘤的治疗选择；然而，其应用受到肿瘤缩小后血脑屏障重建的限制。这项II期试验的目的是评估钇-90（90Y）替伊莫单抗在PCNSL中的治疗效果、毒性和生物分布。10例复发的PCNSL患者被纳入一项II期试验，并接受90Y标记的抗CD20抗体替伊莫单抗治疗。9例患者实际接受了计划的放射免疫治疗。6例患者通过铟-111（111In）替伊莫单抗全身扫描和脑部单光子发射计算机断层扫描（SPECT）测量抗体的生物分布。所有患者在治疗后至少4周接受毒性和反应评估。4例患者有反应：1例患者完全缓解持续30多个月，3例患者有短暂反应（≤4周）。5例患者病情进展，1例患者在给予90Y抗体之前因感染未接受治疗。通过111In替伊莫单抗SPECT成像检查的6例患者中有4例显示抗体在靶点聚集。所有患者均经历3/4级血液毒性，但无急性神经毒性。显示了治疗性抗体可穿透PCNSL并具有显著的临床活性。由于反应持续时间有限和相当大的血液毒性，未来的研究应集中在联合其他化疗并最好有自体干细胞支持的多模式方法上。
