Rituximab and Bendamustine for CNS Involvement by Chronic Lymphocytic Leukemia (P7.261)

OBJECTIVE: To report outcomes in patients with chronic lymphocytic leukemia (CLL) presenting with CNS and leptomeningeal involvement (CNS CLL) treated with intravenous (IV) rituximab and bendamustine (R-benda). BACKGROUND: Chronic Lymphocytic Leukemia (CLL) is a hematologic malignancy characterized by small mature and malignant B lymphocyte proliferation. Autopsy studies have demonstrated CNS involvement in 8-12% of patients, usually as leptomeningeal disease (LMD), or more rarely as parenchymal involvement, though presentations with clinical symptoms are rare. This likely reflects transformation to diffuse large B cell lymphoma in the majority of cases. The prognosis of CNS CLL is poor, with an average survival of 12 months and no standard treatment. R-benda is a highly effective regimen in CLL, but penetration through the blood-brain barrier is suboptimal, and the use of this regimen to treat CNS CLL has not been reported. DESIGN/METHODS: Institutional databases were searched to identify patients with CNS involvement by CLL that were treated with R-Benda. RESULTS: Three patients met the inclusion criteria. The first (#1) was a 55 year-old man with optic neuropathy and thoracic myelopathy, with a clinical presentation resembling multiple sclerosis. Neuroimaging showed periventricular and spinal cord lesions. The second (#2) was a 53-year-old woman presenting with seizures and a left frontal lesion. The third (#3) was a 73 year-old woman presenting with thoracic and lumbar multi-radiculopathy. All patients had pleocytosis and CSF involvement by CLL, confirmed by flow cytometry or gene rearrangement studies. Patients received 5-6 cycles of R-benda, which were well tolerated and resulted in a complete response in all, as measured by follow up imaging and CSF analysis. The progression-free survival from diagnosis was 20 months for patient #1, 44+ months for #2 and 8+ months for #3. The overall survival was 42 months (#1), 47+ months (#2) and 8+ months (#3). CONCLUSIONS: In this selected group of patients with CNS CLL, the R-benda regimen was safe and efficacious, warranting further investigation. Study Supported by: NA