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. Signal Transduction and Targeted Therapy - Long-term follow-up demonstrates the curative potential of dual CD19/CD22 CAR-T-cell therapy alone or combined with autologous stem cell transplantation... 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. This was a single-center, investigator-initiated study comprising two independent clinical trials designed to evaluate the efficacy and safety of dual-target CD19/CD22 CAR-T-cell therapy administered either as monotherapy (cohort A) or in combination with ASCT (cohort B) in patients with r/r aggressive B-NHL in whom TP53 mutation and deletions of chromosome 17p [del(17p)] were screened through next-generation sequencing or fluorescence in situ hybridization.28 The inclusion and exclusion criteria for both trials have been previously published.28 Clinical remission rates, long-term efficacy outcomes, safety parameters, and immune cell subset profiles were comprehensively evaluated in relation to disease and treatment characteristics. 5). These included hypothyroidism (n = 3) and atopic dermatitis (n = 2). Additional isolated events included immune-mediated pleural effusion, asthma, posttransplant lymphoproliferative disorder (PTLD), and coronary artery disease. All patients with these complications received appropriate therapeutic management and subsequently recovered. The incidence and distribution of these late AEs did not differ significantly between the two cohorts or different TP53 statuses (Supplementary Tables 4, 5). Univariate and multivariate Cox proportional hazards regression analyses were performed to identify clinical and treatment-related variables associated with OS and PFS in the entire study population (Table 2) or in either cohort (Supplementary Tables 6, 7).

Original title: “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 | Signal Transduction and Targeted Therapy”