The Addition of Rituximab to Combination Chemotherapy with CHOP Has a Long Lasting Impact on Subsequent Treatment in Remission in Follicular Lymhoma but Not in Mantle Cell Lymphoma: Results of Two Prospective Randomized Studies of the German Low Grade Lymphoma Study Group (GLSG).

The addition of Rituximab (R) to combination chemotherapy has been shown to increase the remission rate (RR) and to prolong the time to treatment failure (TTF) both in follicular lymphoma (FL) and mantle cell lymphoma (MCL). The impact of the R-chemo combination on subsequent therapy in remission, however, remains unclear. The GLSG embarked on two parallel studies in FL and MCL comprizing a prospective randomized comparison of R-CHOP versus CHOP alone followed by a second randomization in remission for Interferon alpha maintenance (IFN) versus myeloablative radio-chemotherapy with subsequent stem cell transplantation (PBCT) in patients < 60 yrs. of age while all older pts. received IFN maintenance. In 428 pts. with FL R-CHOP revealed a significantly higher RR (96% vs. 90%, p = 0.011) and a longer TTF (median not reached vs. 2.6 yrs, p<0.0001). From 347 patients evaluable for subsequent treatment in remission 79 younger patients (35 after CHOP and 44 after R-CHOP) received PBCT. 52 younger patients after CHOP and 69 after R-CHOP received IFN maintenance. 122 older cases received IFN (59 after CHOP and 63 after R-CHOP). For IFN treated pts. a significantly longer progression free survival (PFS) was observed after initial therapy with R-CHOP (estimated 2 yrs - PFS: 63% vs. 84%, p = 0.0004) while no differences were encountered at the time of this analysis after PBCT (estimated 2 yrs - PFS for the whole group: 86%). Hence, in FL initial therapy with R-CHOP appears to have a long lasting beneficial effect on PFS which may be in the range that has previously only been achieved by chemotherapy followed by PBCT. Similar to FL a significantly higher RR (94% vs. 75%, p = 0.005) and a longer TTF (median 14 months vs. 21 months, p = 0.0131) was observed in 122 pts. with MCL undergoing the same randomized comparison. In contrast to FL, however, no differences were revealed for the PFS after R-CHOP versus CHOP and subsequent therapy with IFN or PBCT. These data show a differential effect of adding R to CHOP for initial therapy in FL and MCL. In FL the addition of R to CHOP has a long lasting beneficial effect with a substantial impact on subsequent treatment in remission while in MCL the benefit of R seems restricted to the remission induction period only.