ASCO 2016 Abstract #7502: Lenalidomide as Maintenance for Recurrent/Refractory CNS Lymphoma Yields Promising Results in Phase I study

This ASCO 2016 oral abstract presentation took place on Sunday June 5, 9:45am–12:45pm, during the ‘Hematologic Malignancies-Lymphoma and Chronic Lymphocytic Leukemia’ session. This session was chaired by Pr Gilles Salles, Head of the Hematology Department in South Lyon hospitals, Lyon, France.

The presentation of this abstract was given by Dr James L Rubenstein, who is a Professor of Medicine of the University of California, San Francisco.

This phase I study, which began in December 2012, investigated the use of lenalidomide plus rituximab for the treatment of recurrent/refractory Central Nervous System (CNS) and Intraocular Lymphoma. The primary outcome measure was to establish the maximal tolerated dose of lenalidomide in patients, who were followed for the duration of the treatment (an expected average of 4 months). Estimated enrollment for this study was 18 patients, and inclusion criteria included aged 18 years or more, CD20 positivity on previous analysis, and an absolute neutrophil count of >1,500 (growth factors permitted).

This study presents some of the first emerging evidence in support of using lenalidomide as maintenance therapy, as it significantly potentiates TTP after salvage in relapsed CNS Diffuse Large B-Cell Lymphoma (DLBCL) and delays Whole Brain Radiotherapy (WBRT).

Abstract 7502

Background: There is an unmet need for effective biological therapies for relapsed CNS lymphoma. Lenalidomide (CC-5013) is active in ABC-type DLBCL. We demonstrated activity of lenalidomide in preclinical models of refractory CNS DLBCL. These observations are the basis for this first trial of an IMiD monotherapy in CNS NHL, and in patients with inadequate responses to lenalidomide, with intravenous plus intraventricular rituximab (NCT01542918). In an independent cohort, we evaluated lenalidomide maintenance after salvage in relapsed CNS NHL.

Methods: The primary objective was to evaluate safety and efficacy of lenalidomide at 10, 20, 30 mg dose levels in refractory CD20+ CNS NHL. 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 CNS NHL patients.

Results: Thirteen subjects with refractory CNS DLBCL (8 PCNSL, 5 SCNSL; median age 63, range 46-78) were treated on the phase I protocol. 8 achieved > PR with lenalidomide monotherapy: 3 CR’s, 1 PR in brain parenchymal NHL; 2 CR of CSF NHL; 1 CR, 2 PR’s of intraocular NHL. Four maintained CR to lenalidomide > 9 months and two > 1.8 years. An independent cohort of 12 patients with recurrent CNS DLBCL (10 PCNSL, 2 SCNSL; median age 70, range 59-81) received lenalidomide monotherapy (5-10 mg) as maintenance after salvage. With median follow-up of > 18 months, TTP has been impressive: five maintained remissions > 2 years. Among 10 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).

Conclusions: 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. Clinical trial information: NCT01542918.


Rubenstein JL, et al. Phase I investigation of lenalidomide plus rituximab and outcomes of lenalidomide maintenance in recurrent CNS Lymphoma. J Clin Oncol 34, 2016 (suppl; abstr 7502).