Aggressive Lymphoma - Intensive Chemotherapy Significantly Improves Survival And Recurrence In Younger Patients

According to a study published Online First in The Lancet, younger individuals who suffer with diffuse large B-cell lymphomawho received a more intensive chemotherapy regimen in conjunction with rituximab survive considerably longer, and are around two times as likely to remain in remission 3 years later, in comparison to those who receive standard chemotherapy combined with rituximab. 

Outcomes in individuals with lymphoma under 60 years of age have considerably improved over the past 10 years, due to combined treatment with a standard chemotherapy regimen CHOP (doxorubicin, cyclophosphamide, prednisone and vincristine) and the monoclonal antibody rituximab. However, some individuals still relapse after a complete response to treatment, and researchers have yet to establish the best chemotherapy regimen to combine with rituximab.

According to recent investigations, intensive chemotherapy (higher doses with shortened intervals between treatments) may benefit younger individuals with aggressive lymphomas. 

379 participants between 18 to 59 years of age with early intermediate-stage diffuse large B-cell lymphoma (one of the most common and aggressive forms of non-Hodgkin's lymphoma) were randomly assigned to two groups in the investigation, conducted by the Groupe d'Etude des Lymphomes de I'Adulte (GELA).

• One group of participants received four cycles of dose-intensive chemotherapy (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) plus rituximab (R-ACVBP)* at two week intervals
• The other group received eight cycles of standard treatment (R-CHOP) at three week intervals.

After three years the researchers report that:

• Event-free survival (individuals who did not experience unplanned treatment for lymphoma, disease recurrence or progression, or death) was considerably better for participants who received the dose-intensive chemotherapy combined with rituximab (81%) compared to those who received standard treatment (67%).
• The risk of experiencing an event was reduced by 44% with the more intensive chemotherapy.
• Participants who received dose-intensive chemotherapy had a 56% lower risk death, and were 52% less likely to experience disease progression, in comparison to participants who received standard therapy.

However, the chances of experiencing serious adverse effects were considerably raised by increasing the treatment intensity. In particular, hematological and mucosal toxic effects were considerably more prevalent in the dose-intensive group, and a significantly higher proportion of participants experienced febrile neutropenia (38% versus 9%).

The researchers explain: 

"Intensified immunochemotherapy with R-ACVBP represents an alternative to R-CHOP to improve survival in patients younger than 60 years with diffuse large B-cell lymphoma of low-intermediate risk."

The researchers call for additional investigations to identify subsets of individuals who are most likely to benefit from this intensive treatment. 

In a Comment, Julie Vose from Nebraska Medical Center, Omaha, USA, warns: 

"This 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."