First report on a prospective trial with yttrium-90-labeled ibritumomab tiuxetan (Zevalin) in primary CNS lymphoma

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.