Intensified immunochemotherapy with R-ACVBP significantly improved event-free survival (EFS), progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) compared with R-CHOP in younger patients with diffuse large B-cell lymphoma (DLBCL), but at the cost of increased hematologic toxicity. Christian Recher, MD, CHU Toulouse, France, was a lead investigator for the phase II LNH03-2B trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA) and presented the findings at a press conference. Recher said that while the R-ACVBP regimen was associated with greater toxicity, the adverse events were manageable.
From 2003 through 2008, investigators for the open-label study enrolled 380 patients enrolled at 23 French centers. All patients had a diagnosis of DLBCL and an International Prognostic Index score of 1. At baseline, the groups were well balanced regarding patient age (median age, 47 y) and disease stage and characteristics. In each group, 59% of patients were men, 55% had stage II/IV disease, 44% had elevated levels of lactate dehydrogenase, 22% had a mass >10 cm, 28% had B symptoms, 26% had >1 extra-nodal site of involvement, and 13% had bone marrow involvement. The trial’s primary endpoint was EFS, and secondary endpoints included response rate at the end of treatment, PFS, DFS, and OS.
Patients were randomly assigned to receive chemotherapy with an intensified R-ACVBP regimen or standard R-CHOP. Induction R-ACVBP was administered every 2 weeks for 4 cycles. This was followed by sequential consolidation therapy (Table), with each cycle of consolidation therapy administered in 14-day intervals. Standard R-CHOP was given every 3 weeks for 8 cycles, with intrathecal methotrexate administered on day 1 for the first 4 cycles.
At a mean follow-up of 44 months, no significant difference in response rates was observed between the arms. The overall response rate was 92% for the R-ACVBP group and 88% for the R-CHOP arm. The rate of complete remission (CR), including cases of unconfirmed CR, was 82.7% for the R-ACVBP arm compared with 80.3% for the R-CHOP group. The 3-year rate of EFS was significantly better in the R-ACVBP group versus the R-CHOP arm (81% vs 67%, respectively; P
= .0035). The 3-year rates of PFS, DFS, and OS were also significantly better in the R-ACVBP arm (Figure
). At 3 years, 87% of patients in the R-ACVBP arm and 73% of patients in the R-CHOP arm had not experienced disease progression (P
= .0015). The 3-year rate of DFS was 91% for the R-ACVBP arm compared with 80% for the R-CHOP arm (P
= .0019), and the 3-year median OS was 92% in the R-ACVBP group versus 84% in the R-CHOP arm (P
The R-ACVBP arm was significantly more toxic, however, with 42% of patients experiencing serious adverse events compared with 15% of the patients treated with R-CHOP. Patients taking R-ACVBP were more likely to develop grade 3/4 hematologic events and grade 3 mucositis. Recher said the GELA investigators did not evaluate quality of life, but he suspected patients taking the experimental treatment would have had poorer quality of life due to the worse adverse-events profile associated with the regimen.
___________________________________________________________________________Recher C, Coiffier B, Haioun C, et al. A prospective randomized study comparing dose-intensive immunochemotherapy with R-ACVBP vs standard R-CHOP in younger patients with diffuse large B-cell lymphoma. Groupe d’Etude des Lymphomes de l’Adulte (GELA) study LNH03-2B. Presented at: 52nd ASH Annual Meeting and Exposition; December 4-7, 2010; Orlando, Florida.