Yttrium-90-labeled ibritumomab tiuxetan for primary CNS lymphoma

1781 Objectives: Most patients with primary CNS lymphoma (PCNSL) relapse after primary therapy, and standard salvage treatment has not yet been established. The introduction of anti-CD20 monoclonal antibody rituximab expanded treatment options in systemic B-cell lymphoma. Due to its large molecular size, rituximab poorly penetrates the blood-brain-barrier (BBB) limiting its use in PCNSL (1). According to PET investigations however, the BBB is initially leaky in PCNSL and reconstitutes after therapy-induced tumor shrinkage (2). We report first results of treatment with a single treatment course of yttrium-90 labeled anti-CD20-antibody ibritumomab tiuxetan in PCNSL. Methods: Five patients with recurrent PCNSL were enrolled in a phase II trial and received 15 MBq/kg Y-90-ibritumomab tiuxetan IV after administration of rituximab 250 mg/m2 IV seven days and two hours before Y-90-ibritumomab tiuxetan. Response evaluation by contrast-enhanced MRI and PET was scheduled before, one month and three months after treatment as well as every three months thereafter in responders. In three patients SPECT target imaging with gamma-emitting 111-Indium-ibritumomab tiuxetan was performed at different times. Results: To date, response evaluation is available for four patients. Complete response on MRI was seen in one patient with decreased but still detectable FDG-uptake in PET. Partial response was seen in one patient with response duration of 10+ months. Two patients had disease progression, one of whom showed shrinkage of the target tumor but concurrently developed new lesions. Biodistribiution of the antibody was measured in three patients by imaging with In-111-ibritumomab tiuxetan. Preliminary results indicate an increasing target accumulation up to 6 days after injection. Conclusions: To date, this is the first report on a successful treatment of PCNSL with Y-90-ibritumomab tiuxetan and penetration of a therapeutic antibody into PCNSL, warranting further investigation. Research Support (if any): (1) Rubenstein JL, Combs D, Rosenberg J, Levy A, McDermott M, Damon L, Ignoffo R, Aldape K, Shen A, Lee D, Grillo-Lopez A, Shuman MA. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003;101:466-8. (2) Ott RJ, Brada M, Flower MA, Babich JW, Cherry SR, Deehan BJ. Measurements of blood-brain barrier permeability in patients undergoing radiotherapy and chemotherapy for primary cerebral lymphoma. Eur J Cancer. 1991;27:1356-61.