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)

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.