Bridging to CD19 CAR T-cell therapy for large B-cell lymphoma: An analysis of 1,134 patients by the EBMT Lymphoma Working Party and the GoCART Coalition

CD19-directed CAR T-cell therapy (CAR T) is effective in relapsed/refractory large B-cell lymphoma (R/R LBCL), but the role of bridging therapy (BT) remains incompletely defined. We analyzed 1,134 patients with R/R LBCL treated with axicabtagene ciloleucel or tisagenlecleucel between 2018 and July 2023. BT was categorized as polatuzumab vedotin-bendamustine-rituximab (Pola-BR), low-dose regimens, classical salvage chemo-immunotherapy, or radiotherapy. Overall survival (OS) and progression-free survival (PFS) from CAR T infusion were primary endpoints. Overall, 900 patients (79.5%) received BT and 232 (20.5%) did not (No-BT). At lymphodepletion, BT recipients more often had elevated LDH, bulky disease, and ECOG ≥2, yet had higher complete remission rates. Three-year PFS was 34.3% with BT versus 44.7% with No-BT, and OS was 44.4% versus 57.4%. In multivariable analyses, No-BT remained associated with superior OS (HR 0.63, 95% CI 0.49–0.82) and PFS (HR 0.69, 95% CI 0.55–0.87). Improvement in disease status between apheresis and lymphodepletion occurred more often with BT and was associated with improved outcomes (3-year PFS 47.5% vs. 28.9 and 27.7% for stable/worsened disease among BT recipients). BT modality influenced conversion rates but not adjusted OS, PFS, or relapse. Our data suggest bridging therapy may prioritize disease control with minimal toxicity rather than any specific regimen.