Risk factors for CRS and ICANS with tarlatamab in small cell lung cancer and associated efficacy outcomes: Insights from clinical practice

BACKGROUND: Tarlatamab is the preferred second-line therapy for extensive stage small cell lung cancer (ES-SCLC). However, strict eligibility criteria from trials limit the understanding of safety and efficacy in broader patient populations. METHODS: Patients with ES-SCLC treated with tarlatamab after platinum-based chemotherapy at nine cancer centers were included. Predefined univariate subgroup analyses for cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) included age, performance status, disease burden (>3 metastatic tissue types involved), CNS disease, hepatic disease, and oxygen use among others. Efficacy endpoints were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 109 patients were analyzed across several high-risk features. Any grade CRS was significantly associated with high disease burden (p = 0.002), hepatic disease (p = 0.002), and baseline oxygen use (p = 0.034). Any grade ICANS was significantly associated with high disease burden (p = 0.022) and a history of treated or untreated CNS disease (p = 0.015). Within the subgroup of patients with CNS disease unstable brain metastasis was associated with higher any grade ICANS (p = 0.021). The ORR was 33.7%, PFS of 3.58 months, and median OS of 8.48 months. CNS-specific ORR was 33.3%, including four complete responses without radiation. CONCLUSION: High disease burden, hepatic disease, and baseline oxygen use may increase CRS risk with high disease burden and CNS disease driving ICANS risk. Tarlatamab demonstrated manageable toxicity with clinically relevant efficacy across high-risk patient populations supporting broad access to this therapy.