Tarlatamab-induced immune-related adverse events: Retrospective real-world pharmacovigilance study using FAERS database.

e24106 Background: Food and Drug Administration (FDA) approved Tarlatamab, a bispecific T-cell engager (TCE) demonstrating promising survival outcomes in patients with Extensive-stage small cell lung cancer (ES-SCLC). However, it is associated with significant adverse events (AEs), including cytokine release syndrome (CRS) in 50-60% of patients, and immune effector-associated neurotoxicity syndrome (ICANS) in 8%-28%, but with 0% mortality as observed in the landmark DeLLphi-301 trial. We aimed to review the real-world (RW) data on immune-related adverse events like CRS, ICANS, and non-ICANS neurotoxicity using the FDA Adverse Event Reporting System (FAERS) database. Methods: We queried FAERS using a search-by-product strategy using the terms “Tarlatamab” and “Tarlatamab Dlle” on 22nd January 2025 and retrieved 2 results showing 185 adverse events (AEs). Descriptive statistics were carried out, and disproportionality analysis was done by calculating the reportable odds ratio (ROR) with 95% confidence intervals (CI). ROR was considered significant when the lower limit of the 95% CI was > 1. Results: A total of 185 AEs were reported with Tarlatamab, with immune system disorders (n=73,39.4%) and Nervous system disorders (n=69,37.2%) representing the largest systems of AEs. CRS is the single most common AE reported (n=73,39.4%) followed by ICANS (n=48, 25.9%). 28% (n=21) of CRS patients were hospitalized and 25% (n=7) of them died. Similarly, 35.4% (n=17) required hospitalization for ICANS, and 23.5% (n=4) of them died. Overall CRS is associated with 8% mortality and ICANS is associated with 9% mortality. ROR with Tarlatamab for CRS was 1628.6 (1212.0, 2188.7), ICANS was 2321.5 (1689.9, 3194.8) and non-ICANS neurotoxicity was 3.29 (2.11, 5.11). (Table) Conclusions: Our study revealed CRS and ICANS as the most common AEs, associated with high mortality rates compared to the pivotal trial. (8% in thevs 0% in the clinical trial). This may reflect a broader selection of patients in real-world settings. Better patient selection and preemptive management strategies for high-risk patients must be explored. Baseline demographics and adverse events profile. Baseline characteristic feature Total events (n=185) CRS (n= 73) ICANS (48) Non-ICANS Neurotoxicity (n=22) Total number of adverse events 185(100%) 73 (39.4%) 48 (25.9%) 22 (11.8%) Age groups18-6465-85 15 (8.1%)18 (9.7%) 3 (4.1%)8 (10.9%) 3 (6.30%)7 (14.5%) 3 (13.6%)3 (13.6%) GenderMaleFemale 49 (26.4%)63 (34.0%) 20 (27.3%)24 (32.8%) 12 (25.0%)20 (41.6%) 3 (13.6%)14 (63.6%) OutcomesDiedHospitalized 22 (11.8%)48 (25.9%) 7 (9.5%)21 (28.7%) 4 (8.3%)17 (35.4%) 1 (4.6%)7 (31.8%) ROR (95% CI) - 1628.6 (1212.0, 2188.2) 2321.5 (1686.9,3194.8) 3.29 (2.11,5.11) CRS: Cytokine release syndrome; ICANS: Immune effector cell associated neurotoxicity syndrome; ROR: Reportable Odds ratio.