Long-term follow-up demonstrates the curative potential of dual CD19/CD22 CAR-T-cell therapy alone or combined with autologous stem cell transplantation in TP53-altered relapsed/refractory B-cell non-Hodgkin lymphoma

Abstract The prognostic implications of TP53 alterations in patients with relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL) treated with chimeric antigen receptor (CAR) T-cell therapy remain inadequately characterized, particularly with respect to long-term outcomes. We report extended follow-up (median: 77.77 months) of 122 patients with r/r B-NHL who received either dual-targeted CD19/CD22 CAR-T-cell therapy alone (cohort A, n = 65) or following sequential autologous stem cell transplantation (ASCT; cohort B, n = 57). TP53 alterations were identified in 59 patients (48.4%). Within both cohorts, overall survival (OS) and progression-free survival (PFS) did not significantly differ between the TP53-altered subgroup and the wild-type subgroup ( P >0.05). Notably, compared with CAR-T-cell monotherapy, the sequential ASCT-CAR-T-cell approach (cohort B) was associated with improved 5-year OS (70.2% vs. 40.0%) and PFS (64.9% vs. 35.4%). The 5-year cumulative incidence of nonrelapse mortality was 10.7% overall (9.2% in cohort A vs. 12.3% in cohort B). Secondary malignancies occurred in 2.5% of patients, whereas serious infection-related events beyond 3 months post-infusion were observed in 13.6%, supporting a favorable long-term safety profile. Multivariate analysis identified treatment options and the presence of bulky disease as independent adverse prognostic factors for OS and PFS. These findings suggest that dual-target CD19/CD22 CAR-T-cell therapy, particularly when integrated with ASCT, may mitigate the adverse prognostic influence of TP53 alterations, offering sustained clinical benefit with manageable long-term toxicity in r/r aggressive B-NHL.