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

Abstract

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.

• Authors: Sofiane Maza, Philipp Kiewe, Dieter L Munz, Agnieszka Korfel, Bernd Hamm, Kristoph Jahnke, Eckhard Thiel
• Journal: Neuro-oncology (Neuro Oncol) Vol. 11 Issue 4 Pg. 423-9 (Aug 2009) ISSN: 1522-8517 [Print] England
• PMID: 19060176 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Yttrium Radioisotopes
• ibritumomab tiuxetan

Topics

• Adult
• Aged
• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Central Nervous System Neoplasms (immunology, pathology, radiotherapy)
• Female
• Humans
• Lymphoma, B-Cell (immunology, pathology, radiotherapy)
• Lymphoma, Large B-Cell, Diffuse (immunology, pathology, radiotherapy)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (immunology, pathology, radiotherapy)
• Prognosis
• Prospective Studies
• Radioimmunotherapy
• Remission Induction
• Survival Rate
• Tissue Distribution
• Yttrium Radioisotopes (therapeutic use)