Long-term Therapy Outcomes of CD19/22 CAR T Cell Alone or with Autologous Stem Cell Transplantation for Relapsed/Refractory DLBCL

Abstract We conducted a comparative analysis of the long-term efficacy and safety of two single-arm trials for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): CD19/CD22-directed chimeric antigen receptor (CAR19/22) T-cell cocktail therapy alone or combined with autologous stem cell transplantation (ASCT). The study included 124 patients not in remission after bridging therapy. Cytopenia (36.92% vs. 52.54%) and infection (29.68% vs. 28.81%) were the predominant late grade ≥3 adverse events. CAR19/22 T-cell cocktail therapy combined with ASCT achieved a higher overall response rate (best overall response: 78.46% vs. 93.22%, P = 0.023) and superior progression-free survival (median, 5.68 months vs. not reached, P < 0.001) and overall survival (median, 27.61 months vs. not reached, P < 0.001) than CAR19/22 T-cell cocktail therapy alone. Independent predictors of longer progression-free survival and overall survival included achieving a complete response at 3 months and receiving combination therapy. The associations remained statistically significant after adjustment in sensitivity analyses incorporating propensity score matching and inverse probability of treatment weighting. Significance: CAR19/22 T-cell therapy combined with ASCT significantly improves response and survival in R/R DLBCL, including high-risk patients. This approach seems to enhance the efficacy–safety balance and offers a clinically actionable strategy to optimize CAR T-cell combination therapies.