Allogeneic HCT as Consolidation in B-cell Lymphomas After Exposure to Bispecific Antibodies: A GETH-TC Study

Abstract

Bispecific antibodies (BsAb) targeting CD20 and CD3 have shown efficacy for relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), but their impact on outcomes following allogeneic hematopoietic cell transplantation (alloHCT) remains unclear. In this international, retrospective study, we compared outcomes of adult patients with R/R B-NHL undergoing first alloHCT after BsAb exposure (n=47) versus a historical BsAb-naïve cohort (n=101). Baseline imbalances were addressed using inverse probability of treatment weighting (IPTW) and propensity score matching (PSM). The primary endpoint was non-relapse mortality (NRM); secondary endpoints included overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), graft-versus-host disease (GVHD), engraftment, and GVHD/relapse-free survival (GRFS). In the overall cohort, 2-year NRM did not differ significantly between BsAb-exposed and BsAb-naïve groups (IPTW: 29.1% vs. 31.4%, p=0.80; PSM: 35.8% vs. 27.9%, p=0.43). CIR was significantly lower in BsAb-exposed patients after IPTW (7.4% vs. 20.0%, p=0.01), but not in PSM (9.5% vs. 23.4%, p=0.06). OS, GVHD, GRFS, and engraftment were comparable. In a pre-specified subanalysis limited to large B-cell lymphomas, CIR differences were consistent across IPTW (6.1% vs. 21.1%, p=0.01) and PSM (9.2% vs. 33.3%, p=0.03), reinforcing a potential benefit of prior BsAb therapy. A significant improvement in PFS was observed in this subgroup with IPTW (55.5% vs. 36.6%; p=0.04), but not in PSM (p=0.20). Prior BsAb exposure does not adversely impact alloHCT safety and may be associated with improved disease control. Prospective studies are warranted to define optimal sequencing in this high-risk population.