Glofitamab is superior to non a-CD3xC20 treatments for patients with diffuse large B-cell lymphoma who are refractory or relapse immediately after anti-CD19 CAR T-cell therapy: Final results of the bicar study (LYSA) and indirect comparison with a synthetic control arm from the descart registry.

Abstract Introduction. Chimeric antigen receptor T-cells (CAR T-cells) have improved outcomes for patients (pts) with relapse or refractory diffuse large B-cell lymphoma (R/R DLBCL). However, relapse or progression after CAR T-cell therapy is associated with a short overall survival (mOS), especially when CAR T-cell therapy was administered in the third line or later. We then conducted a phase II trial (BiCAR study, LYSA) testing glofitamab, a 2:1 CD20xCD3 bispecific antibody, with a rapid ramp-up in patients with DLBCL relapsing immediately after CAR T-cells. The primary endpoint was met in June 2023 with a mOS of 14.7 mo (Cartron et al. Nat Cancer 2025). We report the final analysis of the BiCAR study and a prespecified comparison with a synthetic control arm, including patients who were enrolled in the DESCAR-T registry 6 mo) after CAR T-cells therapy compared to 11.1 mo (95% CI: 5.5-20.0) for refractory and early relapse patients (P=0.01). The OS comparison with the synthetic arm from the DESCAR-T registry (n=125) HR 0.490 0.306;0.786, p-value 0.0072, e-value: 2.654. Sensitivity analyses using different weighting, missing data handling methods and testing impact of heterogeneity of data soucres confirmed the robustness of the results. Conclusion The final analysis of the BiCAR study confirmed that glofitamab used for DLBCL in the first relapse or progression after CAR T-cell therapy significantly improves OS. An indirect comparison with patients included in the DESCAR-T registry showed that glofitamab is the best option for those patients.