Benefit of the Adjunction of Rituximab in Salvage Regimen before Autologous Stem-Cell Transplantation (ASCT) in Follicular Lymphoma at Relapse. A Single Institution Study.
Authors: Belhadj Karim , Hicheri Yosr , Pautas Cécile , Gnaoui Taoufik El , Hémery François , Copie-Bergman Christiane , Beaumont Jean-Louis , Delfau-Larue Marie-Hélène , Dupuis Jehan , Gaillard Isabelle , Diviné Marine , Reyes Félix , Haioun Corinne 
Published: October 2019

Follicular lymphomas have an indolent evolution with a median survival ranging between 8–10 years. At relapse, high-dose therapy followed by autologous stem-cell transplantation (ASCT) can be considered as an alternative to conventional chemotherapy. However, efficacy of this strategy remains controversial.

The purpose of our retrospective study is to evaluate ASCT in the pre and post rituximab era as consolidation after 2nd or 3rd remission (at least PR).

Between March 1989 and Apr 2004, 54 pts were treated at relapse with ASCT in our institution. At initial diagnosis, median age was 47 yrs (range 24–61) and FLIPI score was ≥ 3 in 18%. ASCT was performed in 2nd remission in 43 cases and in 3rd remission in 11 [median delay diagnosis-ASCT=44 months (range 7–139) and 53 months (range 21–227), respectively]. The conditioning regimens used were: VP16/cyclophosphamide/TBI in 33 cases, cyclophosphamide/TBI in 9, BEAM in 10 and cyclophosphamide/busulfan in 2. After ASCT, 49 pts achieved CR, 4 achieved PR and one pt progressed. In Dec 2004, with a median follow-up of 4.7 yrs, 27 pts (50%) had relapsed after ASCT with a median time to relapse of 12 months (range 2–95) and 18 pts have died. Causes of death were: lymphoma recurrence in 8 cases, secondary malignancy in 6 cases (3 MDS/AML, 2 radiation-associated solid tumors, 1 EBV associated lymphoma after a new salvage treatment including allogenic transplantation), and late infection in 4 cases, 2 of them occurring in remission (varicella and septicaemia) and 2 others after a new salvage therapy (cellulitis during chemotherapy-induced neutropenia and HHV6 encephalitis after allogenic transplantation). Ten-year overall survival (OS) from initial diagnosis was 68%. Five-year OS and event-free survival after ASCT were 74 and 52%, respectively.

Patients treated at relapse before 1998 did not receive rituximab (rituximab-naive pts: n=29) and those treated after 1998 received a rituximab-based salvage regimen before ASCT (rituximab-treated pts: n=25). The main characteristics of the two populations were as indicated in the table below:

rituximab-naive group rituximab-treated group N 29 25 FLIPI at initial diagnosis (Low/Intermediate/High) % 41/48/11 27/46/27 Median age at ASCT (yrs) 50 (range35–60) 52 (range 30–62) ASCT performed in 2nd remission 23 20 ASCT performed in 3rd remission 6 5 Median duration of response following last treatment line prior to ASCT (months) 21 (range 1–91) 11 (range1–49)

After adjusting for the follow-up (median follow-up of the rituximab-treated group: 3.8 yrs), comparison between the two groups of pts treated with ASCT at relapse shows a significantly better OS of the rituximab-treated group as compared to that of the rituximab-naïve group (100 vs 61% at 4 years, p=0.01). These data suggest that the well-established efficacy of rituximab in FL is not abrogated by consolidative ASCT delivered at relapse in pts not previously treated with rituximab and further emphasize the superiority of immunochemotherapy over chemotherapy alone.