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).

Risk factorsRelative risk (95%CI)P-value
OS   
TBI versus BEAM 0.8 (0.7–1.0) 0.06 
Disease status at BMT (all categories vs CR1,PR1,VGPR1)   
Primary refractory, stable disease, relapse, progression 1.4 (1.1–1.8) 0.001 
CR> 1, PR>1 0.9 (0.7–1.2) 0.6 
Unknown 1.2 (0.8–1.8) 0.5 
Age (for 1 year increase) 1.02 (1.01–1.03) <0.001 
Previous MoAb vs none 0.7 (0.6–0.9) 0.003 
Time from diagnosis to ASCT >1 year (vs <1year) 1.3 (1.02–1.6) 0.03 
BM vs PB 1.7 (1.2–2.3) <0.001 
EFS   
TBI vs BEAM 0.7 (0.6–0.8) <0.001 
Age (for 1 year increase) 1.0 (1.0–1.01) 0.04 
Previous MoAb vs none 0.8 (0.7–0.9) 0.009 
BM vs PB 1.3 (1.0–1.7) 0.04 
NRM   
Age (for 1 year increase) 1.0 (1.0–1.04) 0.04 
Time from diagnosis to ASCT >1 year (vs <1year) 1.6 (1.04–2.5) 0.03 
Female vs male 0.7 (0.5–0.9) 0.02 
Previous MoAb vs none 0.6 (0.4–0.8) 0.005 
BM vs PB 2.0 (1.2–3.6) 0.007 
IR   
TBI vs BEAM 0.7 (0.6–0.8) <0.001 
Disease status at BMT (all categories vs CR1,PR1,VGPR1)   
Primary refractory, stable disease, relapse, progression 1.5 (1.3–1.9) <0.001 
CR> 1, PR>1 1.0 (0.8–1.3) 0.8 
Unknown 1.0 (0.7–1.5) 0.8 
Risk factorsRelative risk (95%CI)P-value
OS   
TBI versus BEAM 0.8 (0.7–1.0) 0.06 
Disease status at BMT (all categories vs CR1,PR1,VGPR1)   
Primary refractory, stable disease, relapse, progression 1.4 (1.1–1.8) 0.001 
CR> 1, PR>1 0.9 (0.7–1.2) 0.6 
Unknown 1.2 (0.8–1.8) 0.5 
Age (for 1 year increase) 1.02 (1.01–1.03) <0.001 
Previous MoAb vs none 0.7 (0.6–0.9) 0.003 
Time from diagnosis to ASCT >1 year (vs <1year) 1.3 (1.02–1.6) 0.03 
BM vs PB 1.7 (1.2–2.3) <0.001 
EFS   
TBI vs BEAM 0.7 (0.6–0.8) <0.001 
Age (for 1 year increase) 1.0 (1.0–1.01) 0.04 
Previous MoAb vs none 0.8 (0.7–0.9) 0.009 
BM vs PB 1.3 (1.0–1.7) 0.04 
NRM   
Age (for 1 year increase) 1.0 (1.0–1.04) 0.04 
Time from diagnosis to ASCT >1 year (vs <1year) 1.6 (1.04–2.5) 0.03 
Female vs male 0.7 (0.5–0.9) 0.02 
Previous MoAb vs none 0.6 (0.4–0.8) 0.005 
BM vs PB 2.0 (1.2–3.6) 0.007 
IR   
TBI vs BEAM 0.7 (0.6–0.8) <0.001 
Disease status at BMT (all categories vs CR1,PR1,VGPR1)   
Primary refractory, stable disease, relapse, progression 1.5 (1.3–1.9) <0.001 
CR> 1, PR>1 1.0 (0.8–1.3) 0.8 
Unknown 1.0 (0.7–1.5) 0.8 
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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.

Topics:
autologous stem cell transplant, follicular lymphoma, lymphoma, rituximab, whole-body irradiation, monoclonal antibodies, follow-up, chemotherapy regimen, disease remission, leukemia

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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