Allogeneic transplantation after failure of chimeric antigen receptor-T cells and exposure to bispecific antibodies: Feasibility, safety and survival outcomes.

Abstract

Clinical outcome after chimeric antigen receptor (CAR)-T-cell failure in large B-cell lymphoma (LBCL) is dismal. Allogeneic stem cell transplantation (alloSCT) represents a potentially curative salvage for relapsed/refractory LBCL, although concerns remain regarding its feasibility and safety in patients exposed to CAR-T and bispecific antibodies. Between 2019 and 2025, 83 disease progressions were documented among 170 LBCL patients treated with CAR-T in two academic centres; 69 (83%) started salvage treatment, the most frequent being glofitamab in 38 (55%); among those, we retrospectively analysed outcomes of 35 candidates for alloSCT consolidation. Ultimately, 13 (37%) underwent alloSCT after achieving complete (CR) or partial response. The median number of previous therapies was 5. All patients engrafted; grade III-IV acute graft-versus-host disease (GvHD) occurred in 8% and moderate-to-severe chronic GvHD in 15% of patients respectively. At 18.4-month median follow-up, non-relapse mortality was 0%; all allografted patients are alive in CR; conversely, the outcome of 22 patients not proceeding to transplant was poor, with a median overall survival of 11.7 months and 13 disease-related deaths (59%). Although in a small cohort of patients, our data highlight the potential benefit of alloSCT consolidation in selected responders to salvage regimens despite the extensive prior treatments with T-cell redirecting therapies.