Impact of Rituximab-Based Therapy After Histological Transformation on High-Dose Therapy and Autologous Stem Cell Transplantation in Follicular Transformed Lymphomas
Authors: Calvo-Villas Jose Manuel , Martín Alejandro , Panizo Carlos , Sancho Juan Manuel , Redondo Alba , González-Sanmiguel José David , Sanchez Gonzalez Blanca , Requena Maria José , González-Barca Eva , Rodríguez-Salazar María José , Castro Nerea , Paredes Viviana , Gayoso Jorge , Caballero Dolores 
Published: October 2019

Abstract
Abstract 4478

Background:
The optimal therapy after transformation of follicular lymphoma into diffuse large B-cell lymphoma (DLBCL) is unknown. Most of retrospective registry data and phase II studies suggest a potential benefit of high-dose therapy and autologous transplantation (HDT-ASCT) for patients with transformed lymphoma (TL). Addition of rituximab to CHOP chemotherapy could improve survival in TL. However, the effect of prior rituximab-based therapy upon the efficacy of subsequent autologous stell cell transplantation (ASCT) in TL is still unknown.

Patients and methods:
We have identified the patients with follicular lymphoma who developed confirmed histological transformation to DLBCL treated with HDT-ASCT included in the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL-TAMO) Spanish registry between October 1994 and March 2011. Patients were divided into two groups, according to whether rituximab-based regimens were given (n = 28, ‘R+’ group) or not (n = 22, ‘R-’ group) at the time of transformation. Kaplan-Meier survival curves were estimated, and differences in survival curves between groups were assessed using the log-rank test.

Results:
Fifty patients (23 women) with a histological diagnosis of TL who underwent HDT-ASCT were included. Median age at transplantation was 55 years (range 32–70). Patients had received a median of 2 (range 1–5) chemotherapy regimens prior to ASCT. Median time from diagnosis of follicular lymphoma to transformation was 49 months (range 8–135). Age-adjusted International Prognostic Index (IPI) was 2 or 3 in 11 patients (22%).
Disease status prior to ASCT was first complete remission in 4 patients (8%), second CR in 56% and active diseasein 14%: sensitive disease in 11 (22%) and refractory disease in 3 (6%) patients. Conditioning regimen consisted of BEAM in 92% of patients, BEAC in 4%, and cyclophosphamide /TBI in 4%. With a median follow-up of 61 months, estimated overall survival (OS) and progression-free survival (PFS) at 5 years after ASCT were 56.5% and 51.3%, respectively. No patients died of transplant-related mortality. Thirteen patients experienced relapse or progression after HD-ASCT; nine of these patients have died because of disease progression. By multivariate analysis three variables significantly influenced both OS and PFS: number of regimens prior to ASCT, disease status at transplant and achievement of response after HD-ASCT. Age-adjusted IPI at transformation had significant influence only on OS.
Patients who did not receive rituximab-based regimens had similar characteristics to patients who received rituximab at transformation. Patients in the R+ group had similar 5-year PFS (48.2% vs 48.4%, P = 0.359) and 5-year overall survival (OS) (66.4% vs 67.2%, P = 0.607) compared to patients in the R- group (Figures 1 and 2). Eight out of 28 “R+” patients had not received rituximab prior to transformation; these patients had better PFS (69% vs 38%, p = 0.912) and OS at 5 years (74.1% vs 54.5%) compared to the 20 patients who were treated with rituximab prior to transformation, but the difference did not reach statistical significance (p >0.1). Patients treated with rituximab-based regimens at any time prior HDT-ASCT had similar OS (70% versus 63.8% at 5 years, P = 0.697) and PFS (50% versus 44% at 5 years, P = 0.445) than patients who received chemotherapy alone before ASCT.

Conclusion:
Our results show that HDT-ASCT remains a valuable therapeutic choice for patients with histological confirmed TL since it allows a long-term disease control in a significant proportion of patients. The addition of rituximab to conventional chemotherapy after transformation does not appear to improve the outcomes of subsequent ASCT, although larger prospective studies are required.

Disclosures:
No relevant conflicts of interest to declare.