Autologous Stem Cell Transplantation Using BEAM Conditioning Is Highly Effective in Patients with Follicular Lymphoma Regardless of Prior Rituximab Exposure
Authors: Kothari Jaimal , Ljubic Antonia , Peggs Karl S , Thomson Kirsty , Morris Emma , Virchis Andres E. , Lambert Jonathan , Goldstone Anthony H , Linch David C , Ardeshna Kirit M 
Published: October 2019

Abstract
Abstract 2025
The benefit of high dose therapy and autologous stem cell transplant (HDT-SCT) using cyclophosphamide/total body irradiation conditioning in patients with relapsed follicular lymphoma (FL) has been demonstrated in the pre-rituximab era (European CUP trial. Schouten JCO 2003 21 3198). The long term outcome following HDT-SCT using BEAM (carmustine 300mg/m2 on d-6, cytarabine 200mg/m2 bd iv on days −5 to −2, etopside 200mg/m2 on days −5 to −2 and melphalan 140mg/m2 on d-1 with stem cell return the next day) conditioning is less well documented. It also remains unknown whether BEAM SCT is of similar efficacy in patients who have previously received rituximab compared with those who were rituximab naïve prior to SCT. In addition the optimal timing for HDT-SCT remains contentious. In order to try and resolve some of these uncertainties we undertook a retrospective analysis of all patients who have undergone BEAM SCT for FL in our institution.
Eighty patients (53 male, 27 female) with FL underwent BEAM SCT between 1988 and 2009; all but 2 of these patients received their transplant after 1994. The median time from diagnosis to HDT was 2.8 years (range 0.5– 32.8). The median age at transplant was 52 (range 34–67). The median number of lines of therapy prior to SCT was 3 (range 1–5). The majority were transplanted in either their 2nd (n=41) or 3rd (n=20) response, with 13 in their 1st, and 6 in their 4th or subsequent response. Eight of the 13 transplanted in 1st response had received 2 or more lines of therapy prior to HDT-SCT. Forty-six patients (63%) received rituximab (either as a monotherapy or in combination with chemotherapy) as a treatment line before SCT.
The median follow up is 6.8 years (range 0.1–19.2). The 7yr overall survival (OS) and progression free survival (PFS) of the whole group as measured from the date of the transplant were 75.6% and 59.5% respectively. The median OS has not yet been reached (NYR) whilst the median PFS is 12.5yrs. Excluding patients transplanted in 1st remission, the 7yr OS, PFS, median OS and median PFS were 74.6%, 58.0%, NYR and 9.4yrs respectively. There were highly significant differences in survival outcomes for patients transplanted in 2nd versus 3rd response: 7yr OS was 83.5% vs 61.1% (p=0.0201) and 7yr PFS was 67.0% vs 42.1% (p=0.0125) respectively (Fig1a). To date there have been no overt relapses after 6yrs in patients transplanted in 2nd response, with the caveat that patients have not been subjected to regular follow up imaging if they have no clinical symptoms or signs of relapse.
When patients who had received rituximab prior to HDT-SCT were compared to those who had not there were no significant differences: 7yr OS 81.4% vs 67.6% (p=0.152) and 7yr PFS 68.0% vs 46.8% (p=0.221) (Fig1b). When analysis was restricted only to patients transplanted in 2nd response, once again no significant differences were found according to prior rituximab exposure: 7yr OS 87.1% vs 76.2% (p=0.297) and 7yr PFS 72.2% vs 53.8% (p=0.125).

Conclusions:
HDT-SCT using BEAM conditioning appears to be highly efficacious with long PFS and OS times. In our series, patients transplanted in 2nd response fare significantly better than those transplanted in 3rd response though further follow up is needed to clearly establish whether a plateau has been reached in the former group. Finally we have shown that treatment with a rituximab-containing regimen prior to BEAM-SCT does not lessen the benefit of BEAM-SCT when compared with patients who had not received rituximab prior to BEAM-SCT. BEAM-SCT therefore remains a valid treatment option for patients with FL in the rituximab era.

Disclosures:
Ljubic: Roche: Salary funded by a grant.