Survival improved significantly for persons younger than 60 years with diffuse large B-cell lymphoma, one of the most common and aggressive forms of non-Hodgkin lymphoma, when they underwent intensified immunochemotherapy compared with the standard regimen. These patients were also approximately twice as likely to remain in remission 3 years later.
Groupe d’Etude des Lymphomes de l’Adulte and Amgen funded the open-label randomized trial in which Groupe investigators compared two regimens: dose-intensive rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (R-ACVBP), administered in four cycles at 2-week intervals; and eight cycles of standard rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP), administered at 3-week intervals. The 379 subjects were aged 18 to 59 years and had untreated diffuse large B-cell lymphoma.
After a median follow-up of 44 months, the 3-year estimate of event-free survival (no unplanned treatment for lymphoma, no disease progression or recurrence, no death) was 81% for the group receiving intensive-therapy R-ACVBP and 67% for the group receiving standard R-CHOP regimen. Three-year estimates of progression-free survival and overall survival were also higher with R-ACVBP, at 87% vs 73% and 92% vs 84%, respectively. Grade 3-4 hematologic toxic effects were more common in the R-ACVBP group, with a higher proportion of patients experiencing a febrile neutropenic episode (75 of 196, or 38%, compared with 16 of 183, or 9%). Nearly half (42%) of the intensive-therapy patients experienced serious adverse events overall, compared with 15% of the standard-therapy participants.
The investigators described the toxic effects of the intensive regimen as raised but manageable (The Lancet. 2011;378:1858-1867). In an accompanying Comment (pp.1828-1829), Julie M. Vose of Nebraska Medical Center in Omaha cautioned that the dose-intense regimen should only be used in patients in whom the expected relapse rate is sufficient to justify the higher toxic effects and cost profile.