In Search of Long-term Disease Control:CAR T-cell Therapy with Axicabtagene ciloleucel or Allogeneic Hematopoietic Cell Transplantation against Relapsed/Refractory Large B-cell Lymphoma

Background : Large B-cell lymphoma (LBCL) represents a challenging scenario in the relapsed/refractory (r/r) setting. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has become the preferred cellular immunotherapy for r/r LBCL, whereas allogeneic hematopoietic cell transplantation (allo-HCT) remains a potential salvage option. Comparative real-world data between both approaches are limited. We aimed to compare outcomes after axicabtagene ciloleucel (axi-cel) and allo-HCT in patients with r/r LBCL. Patients and Methods : We conducted a retrospective single-center real-world analysis comparing outcomes of allo-HCT and CD19-directed CAR T-cell therapy with axicabtagene ciloleucel (axi-cel). A total of 187 patients with r/r large B-cell lymphoma (r/r LBCL) were included. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included relapse incidence (RI), non-relapse mortality (NRM), and treatment-related toxicities. Propensity score matching (PSM) was performed to adjust for baseline differences. Results : Response rates and relapse incidence were comparable between groups. However, NRM was significantly higher after allo-HCT (12% vs. 36%; p = <0.001), mainly driven by infections and graft-versus-host disease. Consequently, axi-cel was associated with superior survival, with 12-month PFS of 50.1% vs. 33.8% and OS of 60.5% vs. 43.2% (both p<0.05). These findings were confirmed in subgroup analyses (≥3rd line) and propensity score–matched cohorts, where axi-cel demonstrated markedly prolonged PFS and OS. Multivariable analyses identified primary refractoriness and poor performance status as adverse prognostic factors, while treatment modality mainly impacted NRM rather than relapse risk. Among patients with chemosensitive disease prior to cellular therapy, PFS and OS were comparable between allo-HCT and axi-cel recipients, whereas CAR T-cell therapy was associated with significantly improved outcomes in patients with chemorefractory disease. Conclusion : In conclusion, axi-cel provided superior PFS and OS to patients with r/r LBCL compared with allo-HCT, primarily due to lower treatment-related mortality and improved disease control in patients with chemorefractory disease prior to cellular therapy.