Sequential R-CHOP and R-FM Chemotherapy Followed By Autologous Stem Cell Transplantation Results In High Rates Of Long Term Remission In Advanced Follicular Lymphoma

Autologous stem cell transplantation (ASCT) is a potentially curative treatment option for relapsed Follicular Lymphoma (FL) patients, but to date available data do not support the use of ASCT as first line consolidation, given the lack of overall survival (OS) advantage compared to standard therapy. R-CHOP (Rituximab-Cyclophosphamide, Vincristine, Doxorubicin, Prednisone) and R-FM (Rituximab, Fludarabine, Mitoxantrone), have comparable efficacy and are widely used as first and second line combinations. The best way to sequence the available therapies in FL is still undefined. Here we show the long term results of a phase II trial of sequential chemotherapy alternating CHOP and FM plus Rituximab followed by ASCT in patients with stage III-IV and/or bulky FL either at disease onset or first relapse, conducted in our Institution from 2002 to 2008.

Patients at diagnosis or first relapse were treated in sequence with R-CHOP for 4 cycles, Endoxan 7g/m² followed by hematopoietic stem cell harvest, R-FM for 4 cycles and ASCT. The ASCT conditioning schedule was BEAM (BCNU, ARA-C, Etoposide, Melphalan) in all cases.

24 patients were enrolled, 12 pts were male. Median age was 44 years. One patient did not undergo ASCT for insufficient left ventricular ejection fraction and was excluded from the analysis. 13 patients were treated upfront whereas 10 patients at first relapse. After a median follow-up of 10 years, progression free survival (PFS) and OS in the whole study cohort were respectively 65% and 87%, with a complete response (CR) rate after the completion of sequential treatment of 100%. PFS and OS for patients treated at disease relapse were 60 and 70% (4 relapses, 3 deaths). Remarkably PFS and OS for the 13 patients treated upfront was 70% and 100% (4 relapses). To date no secondary malignancies were observed.

Sequential treatment alternating standard R-CHOP and R-FM followed by ASCT results in impressive long term PFS and OS rates, both in first line and at relapse. These data represent the proof of principle of a sequential therapy containing alternating alkylating agents and purine analogs followed by ASCT in FL.

No relevant conflicts of interest to declare.