Allogeneic Transplantation after Myeloablative Rituximab/BEAM ± Bortezomib for Patients with Relapsed/Refractory Lymphoid Malignancies: 5-Year Follow-Up Results

Abstract

Although bortezomib and rituximab have synergistic activity in patients with lymphoma and both can attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem cell transplantation (alloSCT). In this phase I/II trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 to 1.3 mg/m2 per dose) was administered i.v. on days -13, -6, -1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results with an historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and matched unrelated donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m2. The weighted cumulative incidences of grades II to IV and III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival was not reached in patients age ≤ 50 years and with a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤ 50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.

Trial registration: ClinicalTrials.gov NCT01538472.

Keywords: Bortezomib; Lymphoma; Myeloablative allogeneic transplantation; R-BEAM.

Conflict of interest statement

Conflicts of interest statement: The Authors declare no conflict of interest.

Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

OS and PFS of patients who received R-BEAM with bortezomib.

Figure 2.

(A) Weighted cumulative incidence of grade II-IV acute GVHD (aGVHD II-IV) in patients who received R-BEAM with bortezomib and those who received R-BEAM without bortezomib. (B) Weighted cumulative incidence of grade III or IV acute GVHD (aGVHD III-IV) in patients who received R-BEAM with bortezomib and those who received R-BEAM without bortezomib. (C) Weighted cumulative incidence of chronic GVHD (cGVHD) in patients who received R-BEAM with bortezomib and those who received R-BEAM without bortezomib.

Figure 3.

(A) Weighted OS rates of patients who received R-BEAM with bortezomib and those who received R-BEAM without bortezomib. (B) OS by donor type (sibling vs. MUD) and patient age (≤50 years versus >50 years) in the combined study- and control groups. Median OS was not reached among patients age ≤50 years and who received sibling donors or who had MUDs. Patients age >50 years whose donors were MUDs had worse outcomes.