The Role of Total Body Irradiation (TBI) in the High-Dose Regimen of Patients with Follicular Lymphoma (FL) Treated with Autologous Stem Cell Transplant (ASCT) in the Rituximab Era. A Retrospective Study of the EBMT Lymphoma Working Party
Authors: El-Najjar Inas , Boumendil Ariane , Luan Jian Jian , Thieblemont Catherine , Blaise Didier , Thomson Kirsty , Le Gouill Steven , Lissandre Severine , Rambaldi Alessandro , Jouet Jean-Pierre , Biron Pierre , Martelli Massimo Fabrizio , Tilly Herve , Pohlreich David , Pfreundschuh Michael , Cordonnier Catherine , Crawley Charles , Cahn Jean-Yves , Paul Vernant Jean , Gribben John G. , Cook Gordon , Russell Nigel H. , Ferrant Augustin , Montoto Silvia , Dreger Peter 
Published: October 2019

Abstract
Abstract 502

Background and Aims:
Rituximab has become an essential component of FL treatment, either in combination with chemotherapy or as maintenance. However, there is not much data available regarding the influence of prior rituximab on the survival of patients after ASCT. In addition, there is no consensus regarding the best type of high-dose regimen. The aim of this study is to assess the outcome of patients with FL having ASCT according to the high-dose regimen and previous treatment with rituximab.

Patients and Methods:
Between 1995 and 2007, 7910 patients with FL had their 1st ASCT and were reported to the EBMT registry. A full data set was available for 2233 patients who had ASCT with either TBI containing regimens or BEAM, and constitute the study group. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method, and curves were compared by log-rank test. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression model. Incidence of relapse (IR) and non-relapse mortality (NRM) were calculated by cumulative incidence curves compared by Gray's test. Multivariate analysis of IR and NRM used Fine and Gray model.

Results:
Six hundred and eighty patients received a TBI-containing regimen, and 1553 patients BEAM. Seven hundred and thirteen patients (32%) had been treated with monoclonal antibodies (MoAb) before ASCT (confirmed as rituximab in 665). Patients who had TBI were younger (median age: 47) than patients who underwent BEAM (median age: 49; p<0.001), and were transplanted in 1st remission more frequently (61%) than BEAM patients (44%, p<0.001). In contrast, more patients treated with BEAM had received MoAb prior to ASCT (37%) than TBI patients (21%, p<0.001). Peripheral blood was the source of stem cells in 98% of patients having BEAM in comparison with 92% of patients having TBI (p<0.001). After a median follow-up of 60 months, the median overall survival (OS) for the whole group was 146 months and the median EFS, 72 months.
Multivariate models for analysis of prognostic value of TBI were all adjusted on disease status at transplant, age, previous MoAb, time from diagnosis to ASCT, and source of stem cell and significant risk factors are shown in the table. In addition there was a trend for patients receiving TBI to have a better OS than patients receiving BEAM (p=0.06).
Moreover, females had better EFS (p = 0.011) and OS (p = 0.058) in univariate analysis. However, the gender survival curves did not fulfil the proportional hazards assumption and thus the multivariate analysis of OS and EFS were stratified on gender allowing no estimation of its effect on outcome.

Conclusions:
In contrast to observations made in patients autografted before 1995 (Montoto Leukemia 2007), in the present series (with a shorter follow-up) the beneficial effect of TBI over BEAM in terms of relapse prevention was not counteracted by an increased NRM, resulting in a significantly better EFS with TBI in the rituximab era. Unlike reported for aggressive lymphoma, use of MoAb (rituximab) prior to ASCT had no detrimental impact on outcome and in fact was associated with significantly better OS. The superior survival of female patients in the rituximab era needs to be confirmed in further studies.

Disclosures:
Blaise: Laboratoire Pierre Fabre: Research Funding; Celgene: Research Funding. Rambaldi:Italfarmaco S.p.A.: Consultancy, Honoraria. Gribben:Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.