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First published on December 5, 2008
This version was published on January 1, 2009
Neuro Oncol 2009 11(4):423-429; DOI:10.1215/15228517-2008-108
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Clinical Investigations

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

Sofiane Maza, Philipp Kiewe, Dieter L. Munz, Agnieszka Korfel, Bernd Hamm, Kristoph Jahnke and Eckhard Thiel

Clinic for Nuclear Medicine (S.M., D.L.M.), Department of Hematology, Oncology, and Transfusion Medicine (P.K., A.K., K.J., E.T.), and Department of Radiology (B.H.), Charité-Universitätsmedizin Berlin, Berlin, Germany

Address correspondence to Eckhard Thiel, Department of Hematology, Oncology, and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30/31, 12200 Berlin, Germany (Eckhard.Thiel{at}charite.de).

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 (90Y) ibritumomab tiuxetan in PCNSL. Ten patients with relapsed PCNSL were included in a phase II trial and treated with the 90Y-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 (111In) 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 90Y-antibody administration. Target accumulation of the antibody was demonstrated in four of the six patients examined by SPECT imaging with 111In 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.

Key Words: 90Y ibritumomab tiuxetan • CNS lymphoma • imaging • PCNSL • Zevalin


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