The Outcome of Transplant Strategies for Diffuse Large B Cell Lymphoma in the Last Decade. the EBMT Experience
Authors: Robinson Stephen Paul , Boumendil Ariane , Finel Herve , Schouten Harry C , Dreger Peter 
Published: October 2019

Abstract
Abstract 748

Introduction.
The current standard of care for patients who fail first line therapy for diffuse large B cell lymphoma (DLBCL) comprises salvage chemotherapy and an autologous stem cell transplant (SCT). With the development of effective first line immunochemotherapy studies have suggested that the results of salvage autologous SCT have deteriorated and that alternative strategies are required. Myeloablative (MA) allogeneic SCT for DLBCL has been rarely used due largely to the toxicity of the procedure. Consequently reduced intensity conditioning (RIC) regimens prior to allogeneic SCT have been developed. Given these developments we have studied the outcome of both autologous and allogeneic SCT for DLBCL over the last decade.

Methods.
The EBMT database was searched for patients satisfying the following criteria;- diagnosis DLBCL, diagnosis between 2002 and 2010, age 18–65, first SCT procedure, chemosensitive relapse or primary refractory disease/refractory relapse. Cumulative incidence analysis of non-relapse mortality (NRM) and relapse rate (RR) and Kaplan-Meier estimates of disease free survival (DFS) and overall survival (OS) were calculated.

Results.

Outcomes for patients with chemosensitive relapse.
The 1 and 4 year NRM rates were:- 3.2% and 6.4% for autoSCT, 11.7% and 20% for RIC alloSCT and 20% and 23.9% for MA alloSCT respectively (hazard ratio (HR) RIC allo 4.0, HR MA allo 4.5 both p<0.0001). Time from diagnosis to transplant >1 year was the only other factor associated with a higher NRM. The 4 year RR was 49% for autoSCT, 44.5% for RICalloSCT and 39.4% for MA alloSCT (ns). Only female sex was associated with a lower RR (HR 0.81 p=0.004). The 4 year DFS was 45.5%, 37% and 37% for autoSCT, RICalloSCT and MA alloSCT respectively. The DFS was worse for those patients undergoing a MA alloSCT (HR 1.6 p= 0.007). Female patients (HR 0.88 p=0.05) and those transplanted more than 1 year after diagnosis (HR 0.83 p=0.016) experienced a superior DFS. The 4 year OS was 55%, 57% and 42% for autologous SCT, RIC alloSCT and MA alloSCT respectively. The OS was worse for patients undergoing a MA alloSCT (HR 2.2, p=0.0002) and those over the age of 50 at transplant (HR 1.2, p=0.02).

Outcomes for patients with chemosensitive relapse transplanted within 1 year of diagnosis.
In this subgroup of patients 585, 20 and 17 received an autologous SCT, RICalloSCT and MA alloSCT respectively. The 4 year DFS was 44.6%, 51.7% and 50.4% and the 4 year OS was 54%, 75.8%, and 59.8% for autoSCT, RIC alloSCT and MA alloSCT respectively. The cohorts were too small to permit a multivariate analysis.

Outcomes for patients with primary refractory and refractory relapse.
The 1 and 4 year NRM rates were:- 6.6% and 7.3% for autoSCT, 15.4% and 15.4% for RIC alloSCT and 19.2% and 19.2% for MA alloSCT respectively. MA alloSCT (HR 2.9, p=0.004) and female sex (HR 1.7, p=0.04) were the only factors associated with a higher NRM. The 4 year RR was 73% for autoSCT, 81.5% for RICalloSCT and 61.3% for MA alloSCT (ns). Only female sex was associated with a lower RR (HR 0.77 p=0.08). The 4 year DFS was 20.7%, 3.9% and 20.7% for autoSCT, RICalloSCT and MA alloSCT respectively. The DFS was significantly better for female patients (HR 0.82 p= 0.04). The 4 year OS was 28%, 8.6% and 17.9% for autologous SCT, RIC alloSCT and MA alloSCT respectively. In multivariate analysis OS was significantly worse for patients undergoing a MA alloSCT (HR 1.5, p=0.02).
The year of transplant and the use of immunochemotherapy as first line therapy had no impact on transplant outcomes.

Conclusions.
Over the last decade patients with chemosensitive relapse can achieve prolonged DFS following an autoSCT at a rate similar to that observed in the pre-Rituximab era. The NRM following an allogeneic SCT continues to be significant without being associated with lower relapse rates although the outcomes following a RICalloSCT are comparable to those following an autoSCT.

Disclosures:
No relevant conflicts of interest to declare.