R-BEAM versus Reduced-Intensity Conditioning Regimens in Patients Undergoing Allogeneic Stem Cell Transplantation for Relapsed Refractory Diffuse Large B Cell Lymphoma

Abstract

Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients. We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n = 47) or reduced-intensity conditioning (RIC) regimens (n = 23). Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P = .03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P = .48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P = .96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P = .98), and relapse-free survival (RFS; 34.8% versus 34.7%, P = .75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P = .05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P = .04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.

Keywords: Allogeneic stem cell transplantation; Diffuse large B cell lymphoma; R-BEAM; Reduced-intensity conditioning regimen; Transformed diffuse large B cell lymphoma.

Figure 1.

(a) Cumulative incidence curves for grade III-IV acute GVHD (aGVHD) with disease relapse or death as competing risks by group (R-BEAM vs. Reduced intensity). (b) Cumulative incidence curves for extensive chronic GVHD (cGVHD) with disease relapse or death as competing risks by group.

Figure 2.

(a) Kaplan-Meier survival curves for overall survival (OS) by group (R-BEAM vs. Reduced intensity). (b) Kaplan-Meier survival curves for overall survival (OS) by cell of origin (GCB vs. NonGCB).

Figure 3.

(a) Cumulative incidence curves for relapse with death without relapse as a competing risk by group (R-BEAM vs. Reduced intensity conditioning). (b) Cumulative incidence curves for non-relapse mortality (NRM) with relapse as a competing risk by group. (c) Kaplan-Meier survival curves for relapse-free survival (RFS) by group. (d) Kaplan-Meier survival curves for GVHD-free/relapse-free survival (GRFS) by group.