Lena- lidomide has significant sing

Lena- lidomide has significant single-agent activity and a distinct, pleo- tropic mechanism of action in DLBCL and therefore is a strong candidate for inclusion in first-line therapy of aggressive B-cell non-Hodgkin lymphoma.13-15 Lenalidomide demonstrates in vitro synergy with rituximab and cytotoxic therapy22,23 and may reduce drug resistance.24,25 We previously conducted a phase I study demonstrating that lenalidomide can be safely combined with R-CHOP21 without an impact on the dose intensity of R-CHOP.Similar phase I studies with slightly different doses and schedules of lenalidomide conducted by Italian(lenalidomide 15 mg per day on days 1 to 14 of R-CHOP21)and French groups(lenalidomide 25 mg per day on days 1 to 14 of R-CHOP21)also demonstrated the feasibility of lenalidomide and R-CHOP combinations.26,27In this phase II study, we evaluated the efficacy of R2CHOP in first-line therapy of DLBCL.The inclusion criteria were designed to enroll patients similar to those seen in clinical practice.Because DLBCL in the elderly is associated with a worse outcome and because elderly patients have limited options for salvage therapy, this study had no upper age limit.Outcomes of historical control patients treated with R-CHOP(rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone)and study patients treated with R2CHOP(lenalidomide added to R-CHOP)based on germinal center B-cell(GCB)versus non-GCB diffuse large B-cell lymphoma(DLBCL)subtype.(A)Progression-free survival in patients treated with R-CHOP in non-GCB versus GCB DLBCL.(B)Progression-free survival in patients treated with R2CHOP in non-GCB versus GCB DLBCL.(C)Overall survival in patients treated with R-CHOP in GCB versus non-GCB DLBCL.(D)Overall survival of patients treated with R2CHOP in non-GCB versus GCB DLBCL.Indeed, 70% of patients were age 60 years or older and 9% were age 80 years or older.Response rates evaluated by PET and CT21 were high, as expected for immunochemotherapy in patients with newly diagnosed DLBCL.The primary end point of the study was EFS.Because no patients received therapy without progression, EFS was the same as PFS in this cohort.EFS and/or PFS in patients treated with R2CHOP is encouraging, considering that 60% of patients had intermediate-high or high International Prognostic Index scores and compared favorably with a historical cohort of patients treated with R-CHOP alone meeting the same inclusion criteria and having similar characteristics.Toxicity was predominantly hematologic and was similar to expected toxicity from R-CHOP alone.Although neutropenia was common, it was of short duration and was rarely associated with neutropenic complications.Thrombocytopenia was ofshort duration and was not associated with bleeding complications or the need for platelet transfusion.CBC was monitored once per week for all treat- ment cycles, likely resulting in reported high incidence of thrombocytopenia and neutropenia in otherwise asymptomatic patients.There was one death related to toxicity for gut perforation following the first cycle of therapy in a patient with known GI involvement by lymphoma.