A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab As Maintenance Therapy Following R-CHOP Chemotherapy for Patients with High Risk Diffuse Large B-Cell Lymphoma

Abstract

Abstract 3668 Background:Diffuse large B-cell lymphoma (DLBCL) patients with an intermediate/high to high risk international prognostic index (IPI) score are at an increased risk of disease relapse in the first year after completion of standard therapy with R-CHOP. Lenalidomide (LEN), an immunomodulatory drug, enhances the natural-killer cell mediated antibody-dependant cellular cytotoxicity of rituximab in lymphoma cell lines, inhibits angiogenesis, alters cytokine production, and has been shown to have clinical activity against B-cell lymphoma including relapsed DLBCL. Methods:DLBCL patients with high risk features (IPI scores of 3 or greater) who achieved CR after R-CHOP were randomized to LEN (arm A) alone or LEN and rituximab maintenance therapy (arm B) within 12 weeks of last dose of R-CHOP. The primary endpoint of the study was to assess the one year relapse-free survival. We expected that a 25% difference of relapse compared with current standard therapy will have clinical significance. Patients in arm A received LEN at a dose of 25 mg daily for 21 days of 28 days. Patients in arm B received LEN at a dose of 20mg daily for 21 days of 28 days along with rituximab (375mg/m2) on day 8 of even cycles. Treatment on both arms was continued for one year. Treatment was discontinued for disease progression. LEN dose adjustments were incorporated in the protocol. Results:Thirty five patients, 19 arm A/16 arm B, 20 female/15 male, with a median age of 59 yrs were enrolled. The median IPI was 3 for all patients. For patients over the age of 60 the median IPI score was 4 and the median aa-IPI was 3. Two patients received XRT to areas of bulky disease at the completion of R-CHOP prior to start of maintenance. At a median follow up of 22 months, the 2 yr PFS and DFS was 86% and 96% respectively. For patients in arm A and arm B the 2 yr PFS was 92% vs.77% and the 2 yr DFS was 100% vs. 92% respectively (p=0.52). Two patients discontinued treatment due to adverse events. Grade 3–4 toxicities include neutropenia (25%), fatigue (17%), diarrhea (8%), DVT (3%), rash (3%), febrile neutropenia (3%). Related grade 1–2 toxicities include hypothyroidism (11%) and rash (47%). There were no treatment related deaths. Conclusions:Lenalidomide as maintenance therapy demonstrates encouraging clinical activity following standard chemotherapy and results in superior survival outcomes in DLBCL patients with high risk prognostic features. The 2-yr OS was 90% in our study as compared with historical controls of 70%. Our study suggests that maintenance strategy with lenalidomide based therapy may increase cure rate and needs to be prospectively evaluated in a phase III study. Disclosures:Reddy:Celgene: Research Funding. Off Label Use: Lenalidomide in Lymphoma. Park:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Research Funding.