ATIM-27. PHASE I INVESTIGATION OF LENALIDOMIDE PLUS RITUXIMAB AND OUTCOMES OF LENALIDOMIDE MAINTENANCE IN RECURRENT CNS LYMPHOMA

Abstract

There is an unmet need for effective biological therapies for relapsed CNS lymphoma. We demonstrated activity of the immunomodulatory agent lenalidomide (CC-5013) in preclinical models of refractory CNS DLBCL. These observations are the basis for this first trial of IMiD monotherapy in CNS NHL, and in patients with inadequate responses to lenalidomide, with intravenous plus intraventricular rituximab. In an independent cohort we evaluated lenalidomide maintenance in relapsed CD20+ CNS NHL. Primary objective was to evaluate safety and efficacy of lenalidomide at 3 dose levels. Secondary endpoints were to determine: CSF penetration of lenalidomide; feasibility of intraventricular plus intravenous rituximab; TTP of maintenance lenalidomide in an independent cohort of relapsed patients. Fourteen subjects with refractory CNS DLBCL (median age 66) were treated on the phase I protocol. 9 achieved > PR with lenalidomide: 3 CR’s, 1 PR in brain parenchymal NHL; 2 CR of CSF NHL; 1 CR, 3 PR’s of intraocular NHL. Four maintained CR to lenalidomide > 9 months and two > 1.8 years. An independent cohort of 14 patients with recurrent CNS DLBCL (median age 65) received lenalidomide as maintenance after salvage. With median follow-up of > 18 months, TTP has been impressive: five maintained remissions > 2 years. Among 12 CNS DLBCL patients with multiple CNS relapses that received focal XRT or HD-MTX-rituximab salvage, followed by lenalidomide maintenance, TTP at CR 2-4 was >5 X longer than TTP in these patients after standard induction and consolidation chemotherapy, without lenalidomide. P<0.013; Hazard Ratio 3.75. Trough lenalidomide concentration in ventricular CSF was highest at 20 mg dose. Elevated CSF lactate predicted short PFS (p<0.01). Lenalidomide penetrates ventricular CSF and is active in relapsed CNS DLBCL. We provide the first evidence that maintenance lenalidomide significantly potentiates TTP after salvage in relapsed CNS DLBCL and delays WBRT.