Axicabtagene ciloleucel versus tisagenlecleucel in relapsed or refractory diffuse large B-cell lymphoma

Abstract

Abstract Introduction Chimeric antigen receptor (CAR) T-cell therapies have revolutionized the treatment of relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), with axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) both being approved for use. Axi-cel was approved for second-line setting based on studies showing improved outcomes compared to high-dose salvage chemoimmunotherapy followed by autologous hematopoietic stem cell transplantation (HSCT). In contrast, tisa-cel did not demonstrate superiority over traditional salvage therapies in the second-line setting. Although both therapies are currently used in clinical practice, real-world comparative data on the safety of axi-cel versus tisa-cel remain limited. This retrospective study aims to compare the one-year outcomes of axi-cel and tisa-cel in patients with R/R DLBCL, offering practical insights into their outcomes outside of clinical trial settings. Methods A retrospective cohort study was conducted using TriNetX, a global federated health research network that provides access to electronic medical records from approximately 132 million patients, primarily in the United States. Adult patients (≥18 years) diagnosed with R/R DLBCL between January 1, 2022, and January 1, 2024, were identified using ICD-10-CM codes. Patients were categorized into two cohorts: those who received axi-cel and those who received tisa-cel. Propensity score matching (1:1) using nearest neighbor matching with a 0.1 pooled standard deviation caliper was performed for demographics, comorbidities, prior stem cell transplantation, and medications. Study outcomes included 1-year rates of all-cause mortality, all-cause hospitalization, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), anemia, neutropenia, thrombocytopenia, heart failure exacerbation, and acute myocardial infarction. Statistical analyses were conducted on the TriNetX platform, with significance set at P<0.05 (two-sided). TriNetX calculates hazard ratios (HRs) and cumulative incidences (CIs) using R survival package version 3.2-3 with the proportional hazard assumption tested using Schoenfeld residuals. This study does not require Institutional Review Board review or informed consent due to the use of de-identified data. Results Our study identified 1,250 patients with R/R DLBCL, including 1,083 patients who received axi-cel and 167 who received tisa-cel. After propensity score matching (PSM), 160 patients were in the axi-cel group (mean age 61.7 ± 11.8 years; 38.8% female; 73.1% White, 8.1% African American) and 160 patients were in the tisa-cel group (mean age 62.3 ± 16.0 years of age; 39.4% female; 75.0% White, 7.5% African American). Axi-cel group had 45% lower risk of all-cause mortality compared to tisa-cel group (HR: 0.55; 95% CI: 0.34–0.87). However, axi-cel group was associated with higher risks of all-cause hospitalization (HR: 1.33; 95% CI: 1.04–1.70), CRS (HR: 2.19; 95% CI: 1.43–3.36), and ICANS (HR: 2.69; 95% CI: 1.42–5.11) compared to tisa-cell group. No significant differences were observed in anemia (HR: 1.18; 95% CI: 0.82–1.72), neutropenia (HR: 1.30; 95% CI: 0.96–1.77), and thrombocytopenia (HR: 0.96; 95% CI: 0.65–1.43) between these two treatment groups. Additionally, there were no significant differences in terms of septic shock (HR: 0.79; 95% CI: 0.42–1.47), pneumonia (HR: 0.64; 95% CI: 0.34–1.21), and heart failure exacerbation (HR: 1.16; 95% CI: 0.76–1.76) between axi-cel group and tisa-cell group. Conclusion This large and multicenter cohort study provides real-world valuable insights into the one-year comparative outcomes of axi-cel and tisa-cel in patients with R/R DLBCL. Our study suggested axi-cel was associated with lower mortality rate, despites its higher rates of all-cause hospitalization, CRS, and ICANS compared to tisa-cell. These findings highlight the importance of close monitoring and supportive care during the first year following CAR-T therapy to optimize patient outcomes. An important limitation of our study is the lack of data on the number of prior lines of therapy, which may have differed between treatment groups and could have influenced clinical outcomes. Future prospective studies with comprehensive clinical data and inclusion of lisocabtagene maraleucel (liso-cel) would be valuable to provide a more complete comparison across currently available CAR T-cell therapies.