Effect of the addition of rituximab to front line therapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) on the remission rate and time to treatment failure (TTF) compared to CHOP alone in mantle cell lymphoma (MCL): results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG)

English

Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 5 de junio del 2004

This study discusses an off-label use of rituximab for the treatment of MCL.

Presenter: W. Hiddemann
Presenter's Affiliation: Ludwig-Maximilians-University, Munchen, Germany
Type of Session: Scientific

Background

Mantle cell lymphoma (MCL) accounts for up to 6% of all lymphomas. Most patients present with advanced stage and progress rapidly. There is currently no standardized approach for treatment of this disease. Responses to different chemotherapy regimens range between 19% and 52% however, the overall survival remains poor. New treatment modalities are therefore needed. Based on the encouraging results of a previous trial combining rituximab with the fludarabine, cyclophosphamide, mitoxantrone (FCM) regimen for salvage therapy of relapsed MCL, the GLSG started a prospective randomized trial comparing CHOP versus rituximab plus CHOP (R-CHOP) as first line therapy.

Materials and Methods

122 patients with newly diagnosed MCL, stages III and IV were randomized between CHOP (n=60) and R-CHOP (n=62) (the studies included other histologies however, this analysis only include the patients with MCL)

Time to tumor failure (TTF) was defined as time from initial treatment to progression of the lymphoma, and Progression free survival (PFS) was defined as the time from documented remission to relapse

Patients who achieved complete response (CR) or partial response (PR) were subsequently randomized to other treatments (PSCT and IFN maintenance) with different schedules of administration according to age (> or < 60).

Results

Overall, R-CHOP showed significantly better CR rates then CHOP of 34% vs 7% (p=0.00024)

The overall response rate (CR + PR) was also superior for R-CHOP compared to CHOP with 94% vs 74% (p=0.005)

The TTF was significantly longer (p=0.0131) in the R-CHOP group; PFS was not statistically different between the two groups

Toxicity was mild, predominantly comprising myelosuppression and granulocytopenia in particular. Grade III and IV granulocytopenia was more frequent with R-CHOP regimen (63% versus 53%, p=0.01).

Author's Conclusions

R-CHOP produced better CR and overall remissions
R-CHOP produced a longer TTF
There was no differences in PFS between the two regimens
There were no differences in the two post-induction regimens between the the CHOP and R-CHOP groups
R-CHOP did not induce major toxicities

Clinical/Scientific Implications
MCL carries a poor prognosis and there are no standardized regimens. Promising results have been shown with the inclusion of rituximab to the FCM regimen and rituximab has significant clinical activity in MCL as single agent. Unfortunately, the progression free survival and the overall survival remain poor. This study compared CHOP and R-CHOP regimens as first line therapy in patients with MCL. R-CHOP induced better CRs and longer TTF. PFS was not improved by the addition of rituximab. The different regimens applied after CHOP/R-CHOP induction may partly account for the lack of differences in PFS. These data are encouraging and further studies with a larger number of patients with stratification by prognostic risk factors and longer follow-up time to evaluate overall survival are needed.

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