Effect of lenalidomide combined with R-CHOP (R2CHOP) on negative prognostic impact of nongerminal center (non-GCB) phenotype in newly diagnosed diffuse large B-cell lymphoma: A phase 2 study.

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Clinical Science Symposium, Targeted Therapies in Early, Mid, and Late Development
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 8520)
Grzegorz S. Nowakowski, Betsy LaPlant, William R Macon, Craig B. Reeder, James M. Foran, Garth D. Nelson, Carrie A. Thompson, Candido Rivera, David James Inwards, Ivana N. M. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen Maxted Ansell, Thomas Matthew Habermann, Thomas E. Witzig; Mayo Clinic, Rochester, MN; Mayo Clinic, Scottsdale, AZ; Mayo Clinic, Jacksonville, FL; Division of Hematology, Mayo Clinic, Rochester, MN

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Abstract Disclosures


Background: The non-germinal center B-cell like (non-GCB) subtype of diffuse large cell lymphoma (DLBCL) is associated with a worse outcome when treated with RCHOP chemotherapy. Lenalidomide has significant single-agent activity in relapsed DLBCL and might be particularly active in non-GCB DLBCL. We have previously reported that lenalidomide can safely be combined with RCHOP (R2CHOP). This phase 2 study evaluated the efficacy of this combination in newly diagnosed DLBCL and analyzed the outcomes based on DLBCL subtype. Methods: Eligible patients were adults with newly diagnosed, untreated, stages II-IV CD20 positive DLBCL. Patients received oral lenalidomide 25 mg days 1-10 with standard dose R-CHOP every 21 days for 6 cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry (Hans algorithm) and classified as germinal center B-cell (GCB) vs non-GCB in the R2CHOP patients and 87 control DLBCL patients from the Mayo Clinic Lymphoma Database meeting the same inclusion criteria and treated with conventional RCHOP. Results: 64 DLBCL patients were enrolled. Median age was 65 years (22-87) and 34 patients (53%) had IPI intermediate-high or high. 60 were evaluable for response. The overall response rate was 98% (59/60) with 80% (48/60) complete response (CR). 24 month EFS and OS rates (95% CI) were 59% (48%-74%) and 78% (68-90%), respectively. In RCHOP patients, 24 months PFS and OS were 28% vs 64%, p<0.001 and 46% vs 78% p<0.001 in non-GCB patients vs GCB patients respectively. In contrast, there was no difference in 24 months PFS or OS for R2CHOP treated patients based on non-GCB and GCB subtype, 60% vs. 0.59%, p= 0.83 and 83% vs. 75%, p=0.61 at 2 years respectively. Conclusions: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide to RCHOP appears to mitigate the negative impact of non-GCB phenotype on the outcome. A randomized phase 2 study of RCHOP vs. R2CHOP utilizing gene expression profiling classification of DLBCL subtype and led by the Eastern Cooperative Oncology Group (E1412) is currently ongoing. Clinical trial information: NCT00670358.