Intensified Chemotherapy with R-ACVBP Improves Survival in Younger Patients with Diffuse B-cell Lymphoma

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Compared with standard R-CHOP (rituximab [Rituxan], doxorubicin, cyclophosphamide, vincristine, and prednisone), intensified immunochemotherapy with R-ACVBP (dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine [not available in U.S.], bleomycin, and prednisone) significantly improves survival of patients aged 18 to 59 years with diffuse large B-cell lymphoma with low-intermediate risk, according to the International Prognostic Index, researchers from the Groupe d’Etudes des Lymphomes de l’Adulte (GELA) reported in The Lancet. The results are from an open-label phase III randomized trial comparing R‑ACVBP with subsequent consolidation vs standard R‑CHOP.

Eligible patients were aged 18 to 59 years with untreated diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index equal to 1. The authors noted that “rituximab in association with CHOP chemotherapy has substantially improved the outcome of patients with diffuse large B-cell lymphoma. However, the results of the R-CHOP regimen, which has been widely thought the standard of care, remains suboptimum in the treatment of younger patients.”

Trial Details

The multicenter study enrolled 380 patients at 73 hematology or oncology departments of GELA (Group d’Etude des Lymphomes de l’Adulte) in France, Belgium, and Switzerland. All but one received at least one dose of the planned protocol treatment. A total of 54 patients did not complete treatment. The most commonly cited reasons for discontinuance were treatment-related toxic effects in the R-ACVBP group and treatment failure in the R-CHOP group.

At a median follow-up of 44 months, the 3-year estimated event-free survival was 81% in the R-ACVBP group and 67% in the R-CHOP group. The 3-year estimates for progression-free survival were 87% vs 73%, respectively. Overall survival was 92% among patients receiving R-ACVBP vs 84% for patients receiving R-CHOP.

More patients (42%) in the R-ACVBP group experienced a serious adverse event vs 15% in the R-CHOP group. Hematologic toxicities of the intensive regimen were increased but manageable, the authors noted. Grade 3/4 hematologic toxic effects were more common in the R-ACVBP group, with 38% experiencing a febrile neutropenic episode compared to 9% in the R-CHOP group.

“The lower rate of disease progression during the treatment phase and fewer relapses in patients who reached a complete response accounted for the prolonged progression-free survival and overall survival in our R-ACVBP group. However, we do not know which phase of the R-ACVBP regimen improves the outcome,” the researchers commented.

A trial is underway aimed at assessing the quality of remission after R-ACVBP and R-CHOP. ■

Récher C, et al: Lancet 378:1858-1867, 2011.