462 | OUTCOMES AFTER CAR‐T CELL THERAPY (TISAGENLECLEUCEL OR AXICABTAGENE CILOLEUCEL) IN PATIENTS OLDER THAN 70 YEARS WITH DIFFUSE LARGE B CELL LYMPHOMA

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differences in pathophysiology and prior treatments that may promote resistance to conventional therapies.Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is established as standard of care for relapsed/refractory large B-cell lymphoma.However, the prognostic impact of histological subtype remains unclear, as pivotal trials included heterogeneous histologies and provided limited outcome data for TiNHL.Methods: A multicenter, observational, prospective study was conducted using the Italian CART-SIE study, including patients with R/R TiNHL and R/R dnDLBCL treated with commercial anti-CD19 CAR T-cell therapy (axi-cel or tisa-cel) between September 2019 and April 2024.Patients were stratified by histology and compared using a t-test.A sub-analysis was conducted within the TiNHL between transformed follicular lymphoma (tFL) and transformed marginal zone lymphoma (tMZL).The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), relapse incidence/progression of disease (RI/POD), non-relapse mortality (NRM), and incidence of cytokine release syndrome (CRS) and immune effector cellassociated neurotoxicity syndrome (ICANS).Statistical analyses included Kaplan-Meier survival estimation, log-rank tests, Cox regression modeling, and competing risk analysis.Results: Among the 746 evaluable patients, 107 had TiNHL (96 tFL and 11 tMZL), while 331 had dnDLBCL.The two cohorts were largely comparable in most characteristics (Table 1).The ORR was significantly higher in the TiNHL cohort (83% vs. 69%, p < 0.01), along with a greater CRR (61% vs. 53%).At a median follow-up of 21.6 months for TiNHL and 16.3 months for dnDLBCL, TiNHL was associated with superior 2-year PFS (44% vs. 31%, p < 0.01) and OS (61% vs. 48%, p < 0.01).Median PFS was longer in TiNHL (16.6 vs. 4.44 months), as was median OS (47 vs. 19 months).In multivariate analysis, a high hematotox score was associated with an unfavorable impact on PFS (HR = 2.10; 95% CI: 1.19-3.70,p = 0.01) and OS (HR = 3.57; 95% CI: 1.54-8.29,p < 0.01).No significant differences in outcomes were observed between the tFL and tMZL subgroups.The 2-year RI/ POD was lower in TiNHL (23% vs. 42%, p < 0.01), whereas NRM was similar between groups (13% vs. 6%, p = 0.44).Safety profiles were comparable, with similar rates of CRS (79% vs. 85%, pvalue = 0.11) and ICANS (19% vs. 20%, p-value = 0.35).Conclusions: This large real-world analysis demonstrates that patients with TiNHL treated with CAR T-cell therapy achieve superior outcomes compared to those with dnDLBCL, with a comparable safety profile.These findings support CAR T-cell therapy as an effective treatment option for TiNHL, warranting consideration as a standard approach in their treatment algorithm.

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