11021 Background: Axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) are approved CD19-directed CAR T-cell therapies for large B-cell lymphoma (LBCL); however, comparative real-world evidence on their effectiveness and safety remains limited. We conducted a target trial emulation to compare the overall survival (OS), event-free survival (EFS), and safety outcomes between axi-cel vs liso-cel in routine clinical practice. Methods: Using de-identified electronic health record data from TriNetX (January 2017- December 2025), we emulated a two-arm target trial among adult patients with LBCL who received axi-cel or liso-cel. Index date (T 0 ) was defined as the date of CAR T-infusion. Patients with active severe infections at the index date or a history of cardiovascular and central nervous system involvement were excluded. Inverse probability of treatment weighting (IPTW) was used to balance the covariates, including age, sex, race, comorbidity, prior autologous stem cell transplantation, bridging therapy, and baseline inflammatory markers. OS was analyzed using IPTW Cox proportional hazards models. Event-free survival (EFS) was defined as a composite of death or initiation of subsequent systemic therapy (as a proxy for treatment failure). Cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported, and all analyses were conducted using R. Results: Among 1,311 eligible patients, 947 received axi-cel and 364 received liso-cel. In the unweighted cohort, patients treated with axi-cel were younger than those receiving liso-cel (median age 62 vs 72 years), with a similar sex distribution and a predominantly White population in both groups. After IPTW, baseline demographic, clinical, and laboratory characteristics were balanced between groups. OS did not differ significantly between axi-cel and liso-cel (HR 0.98; 95% CI, 0.71-1.36). Median OS was not reached in either group, with similar OS rates at 12 months (axi-cel: 78.1%, liso-cel: 80.3%) and 24 months (axi-cel: 71.3%, liso-cel: 71.4%). EFS was also comparable between treatments (HR 1.08; 95% CI, 0.82–1.44). No significant differences in CRS risk were observed within 90 days or overall follow-up (HR: 0.86; 95% CI, 0.66-1.11). Axi-cel was associated with a higher risk of ICANS within the first 90 days (HR 1.42; 95% CI, 1.00-2.01), although no significant difference was observed over longer follow-up. Conclusions: Axi-cel and liso-cel demonstrated comparable effectiveness in terms of OS and EFS. Safety profiles differed primarily in early neurotoxicity risk, while CRS incidence was similar between products. These findings provide real-world comparative evidence that may help to inform CAR T-cell therapy selection in clinical practice.
Zuber et al. (Wed,) studied this question.