R-CVP vs R-CHOP vs R-FM for the initial treatment of patients with advanced stage Follicular Lymphoma. Results of the FOLL05 trial conducted by the Fondazione Italiana Linfomi (FIL)

Purpose. Although rituximab (R) is commonly used for patients with advanced follicular
lymphoma (FL) requiring treatment, the optimal associated chemotherapy regimen is yet to
be clarified.
Patients and Methods. We conducted an open label, multicenter, randomized trial on
adult patients with previously untreated stage II-IV FL to compare the efficacy of 8 doses of
R associated with 8 cycles of CVP, or 6 cycles of CHOP or 6 cycles of FM. The principal
end point of the study was Time to Treatment Failure (TTF).
Results. There were 534 patients enrolled in the study. The overall response rate was
88%, 93%, and 91% for R-CVP, R-CHOP, and R-FM, respectively (P=0.247). After a
median follow-up of 34 months, the 3-year TTF was 46%, 62% and 59% for the respective
treatment groups (R-CHOP vs R-CVP, P=0.003; R-FM vs R-CVP, P=0.006; R-FM vs RCHOP,
P=0.763). The 3-year progression free survival (PFS) was 52%, 68% and 63%
(overall P=0.011) and the 3-year overall survival was 95% for the whole series. R-FM
resulted in higher rates of grade III-IV neutropenia (64%) compared to R-CVP (28%) and
R-CHOP (50%) (P < 0.001). Overall, 23 second malignancies were registered during
follow-up: 4 in R-CVP, 5 in R-CHOP and 14 in R-FM.
Conclusions. In the present study R-CHOP and R-FM were superior to R-CVP in terms of
3-year TTF and PFS. In addition, R-CHOP had a better risk/benefit ratio compared with RFM.