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 end point was nonrelapse mortality (NRM); secondary end points 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 prespecified 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.