Front - Line Combined Immuno-Chemotherapy (R-CHOP) Significantly Improves the Time to Treatment Failure and Overall Survival in Elderly Patients with Advanced Stage Follicular Lymphoma - Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG).

Follicular lymphoma (FL) is an indolent disease of the advanced age with more than 40 % of the patients being older than 60 years at diagnosis and an age-specific incidence peaking above 75 years. We now analyzed the treatment outcome of elderly patients in the GLSG multicenter phase III study comprising a prospective randomized comparison of R-CHOP versus CHOP alone in patients with advanced stage FL. 221 patients > 60 years with untreated FL were randomized for therapy with R-CHOP (R-CHOP: Rituximab 375 mg/m2 d0–1; cyclophosphamide 750 mg/m2 d1; doxorubicine 50 mg/m2 d1; vincristine 1.4 mg/m2 d1; prednisone 100 mg/m2 d1–5) (n=109) or CHOP alone (n=112). Patient characteristics were well balanced between the treatment groups, also with regard to the distribution of the FLIPI risk groups (≥ 3 adverse factors 73% and 66 % in the R-CHOP and CHOP arm, respectively). R-CHOP induced higher overall response rates and significantly prolonged the time to treatment failure (TTF)(median 5.0 years versus 2.1 years, respectively; logrank test: p<0.0001) compared to CHOP in the elderly patient group. Furthermore, the estimated 4-years progression free survival was 62.2% for R-CHOP versus 27.9 % after CHOP (logrank: p< 0.0001). Importantly, R-CHOP was able to prolong the overall survival in elderly patients compared to CHOP with an estimated 4-years overall survival of 90% after immunochemotherapy versus 81 % after CHOP alone (logrank test: p=0.039). In the multivariate analysis individual FLIPI risk factors such as elevated serum LDH level, a hemoglobin level below 12 g/dl, the number of nodal areas (> 4) as well as application of CHOP alone were independently associated with a shorter TTF. Treatment related side effects were similar in both patient groups and comprised predominantly myelosuppression. In summary, the addition of Rituximab to CHOP significantly improves the outcome of elderly patients with previously untreated advanced stage FL without adding major side effects.