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

¹ Clinic for Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
² Department of Hematology, Oncology, and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
³ Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany
⁴ Department of Hematology, Oncology, and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
⁵ Department of Hematology, Oncology, and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30/31, 12200 Berlin, Germany

^* To whom correspondence should be addressed. E-mail: Eckhard.Thiel{at}charite.de.

	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 (BBB) after tumor shrinkage. The aim of this phase II trial was to evaluate the therapeutic efficacy of ⁹⁰Y ibritumomab tiuxetan in PCNSL, its toxicity and biodistribution. Ten patients with relapsed PCNSL were included in a phase II trial and treated with yttrium-90 (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 computed tomography (SPECT) of the brain. All patients were evaluated for toxicity and response at least four 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 4 of the 6 patients examined by SPECT imaging with ¹¹¹In ibritumomab tiuxetan. All patients experienced grade III/IV hematotoxicity but no acute neurotoxicity. Penetration of a therapeutic antibody into PCNSL and significant clinical activity could be shown. Due to 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^TM

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