Post Market Analysis of Toxicities Reported with Chimeric Antigen Receptor (CAR) T-Cell Therapies and Bispecific T-Cell Engager (BiTE) for Diffuse Large B-Cell Lymphoma (DLBCL) Using the FDA Adverse Event Reporting System (FAERS)

CAR-T and BiTE therapies have improved outcomes in relapsed/refractory (r/r) DLBCL. However, they are associated with unique and potentially severe adverse events (AE) that impact morbidity and mortality. The aim of this study is to compare toxicities and outcomes in patients with r/r DLBCL receiving CAR-T and BiTE therapies through AE reported to FAERS. The FAERS database was queried for AE that occurred with lisocabtagene maraleucel (liso-cel), tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel) (CAR-T), or Epcoritamab and Glofitamab (BiTE) therapies, between January 2022-June 2024. The likelihood of AEs or outcomes (progression, hospitalization, death) occurring with a specific treatment or treatment group (CAR-T vs BiTE) was compared with the reporting odds ratio (ROR) and 95% confidence intervals (CI). CIs that included 1 were considered statistically significant. There were 4,819 cases, of which 2,982 (61.9%) and 1,837 (38.1%) received CAR-T and BiTEs, respectively. BiTEs had higher odds of sepsis (ROR 3.04 [95% CI 2.36, 3.90]), neutropenia (ROR 2.30 [95% CI 2.01, 2.62]), septic shock (ROR 1.99 [95% CI 1.35, 2.94]), and hospitalization (ROR 2.04 [95% CI 1.82, 2.23]. CAR-T had higher reported odds of disease progression (ROR 4.34 [95% CI 3.34, 5.66]), immune effector cell neurotoxicity syndrome (ICANS) (ROR 4.27 [95% CI 3.31, 5.52]), and death (ROR 1.64 [95% CI 1.44, 1.84]). Intergroup comparisons had notable heterogeneity. Axi-cel and Liso-cel had a higher odd of death compared to Tisa-cel (ROR 2.06 [95% CI 1.45, 2.93] and 2.04 [95% CI 1.72, 2.38] respectively). Axi-cel had higher odds of ICANS compared to Tisa-cel (ROR 2.56 [95% CI 2.38, 2.77] or Liso-cel (ROR 1.70 [95% CI 1.39,2.08]. Tisa-cel had higher odds of CRS compared to Axi-cel: ROR 2.38 [95% CI 2.22, 2.56] and Liso-cel (ROR 2.11 [95% CI 1.06, 4.19]). Tisa-cel had less frequent reports of disease progression (ROR 0.27 [95% CI 0.13, 0.56] and 0.20 [95% CI 0.18, 0.21]), pyrexia (ROR 0.28 [95% CI 0.12, 0.65] and 0.36 [95% CI 0.31, 0.43]), and cytopenia (ROR 0.43 [95% CI 0.25,0.74] and 0.29 [95% CI 0.25,0.35]) compared to Axi-cel or Liso-cel. Epcoritamab had increased reports of sepsis (ROR 4.33 [95% CI 2.38, 7.90]), ICANS (ROR 1.93 [95% CI 1.03, 3.62]), infection (ROR 1.74), CRS (ROR 1.42), and hospitalization (ROR 1.46 [95% CI 1.24, 1.73]), while Glofitamab had increased reports of anemia (3.95), disease progression (ROR 3.56 [95% CI 2.53, 5.01]), neutropenia (ROR 1.26), and death (ROR 1.64 [95% CI 1.32, 2.04]). This analysis suggests that CAR-T has a higher reported odds of ICANS, neurotoxicity, and death, whereas BiTEs had a higher reported odds of both infections and hospitalization in patients with r/r DLBCL, with significant intergroup differences. While FAERS has limitations that restrict conclusions of causality, this data informs on specific treatment toxicities that may impact patients and inform treatment decisions.