Treatment of a B-Cell, Primary Central Nervous System Lymphoma Patient with Radioimmunotherapy Using Zevalin®: A Proof-of-Principal Case.

Primary Central Nervous System NHL (PCNSL) has increased in incidence across all age groups over the past decades. 90% are B-cell NHL. Resection has not been shown to improve survival and standard chemotherapy is not effective. While radiation therapy (RT) was formerly the standard therapy, high-dose methotrexate (Mtx) is the single most active agent. High-dose Mtx alone or in combination with RT has resulted in response rates of 100% and median survival ranging between 30–60 months, although the risk of relapse is 50%. The prognosis at relapse is poor; clearly, new strategies are needed for these patients. There are no previous cases or clinical trials to evaluate the efficacy of Zevalin in PCNSL. We report a single patient with PCNSL treated with Zevalin. A 26YO male with a CD20+/CD19+ PCNSL was diagnosed in 05/01 when he presented with a left frontal mass. The patient underwent surgical resection (pathology: pleomorphic xanthoastrocytoma). By 09/01 local progression was documented and a second excision was done. Pathology showed a CD20+/CD19+, PCNSL (previous pathology was reviewed and the diagnosis was confirmed). No systemic disease was found and the patient was HIV negative. While the patient was waiting to start RT, the lesion progressed and a third resection was done, followed by RT. By 01/03 progression was documented by imaging studies but the lesion was found in the right frontal lobe, just across the previous lesion in the left side; diagnosis was confirmed with a stereotactic biopsy. Systemic disease was not documented. PET scan showed area of increased uptake in the right frontal lobe of the brain consistent with active lymphoma with no areas of abnormally increased F-18 uptake in the rest of the body. It was decided to treat the patient with Zevalin RIT. The study utilized the standard Zevalin kit and the preparation, administration and storage were followed in the drug labeling directions. On day 1 he received Rituxan 250 mg/m 2 followed by 5.0 mCi of 111 In-2B8 for biodistribution evaluation. Whole body scintogram planar images were obtained 24 and 48 hours after the infusion of the 111 In-2B8 and they showed increased activity in the right frontal lobe consistent with the patients known lymphoma. Otherwise, there was normal blood pool and organ distribution of the radiolabeled antibody. On day 8 the patient received Rituxan 250 mg/m 2 followed by 29.1 mCi of Zevalin (0.4 mCi/Kg). Tumor localization of radioactivity was evident at 24 hours. The estimated localization per gram of tumor at 24 hours was 0.21% of the injected dose (marrow 0.0042%, liver 0.0069%, kidney 0.0065%, spleen 0.015%). The anticipated hematologic toxicity nadired on week 5 and recovered by week 7. MRI was performed on weeks 6, 14, 20 indicating stable disease with an interval decrease in the right frontal abnormal T2 hyperintensity. PET scan performed on week 20 indicating interval decrease in the right frontal lobe uptake. On week 32, an MRI of the brain and a PET scan showed progression. This report is the first description in humans using Zevalin in PCNSL, and serves as a proof-of-principle. We have proposed a hypothesis-driven pilot study to confirm our observation that Zevalin binds to the PCNSL and it is able to deliver local radiation. If positive, a more definitive design would be pursued. Images (MRI, PET, Indium Scans) will be presented in the meeting.