Safety Signals of CRS and ICANS With Tarlatamab in Relapsed Small Cell Lung Cancer: Insights From a Small Case Study.

Abstract

Background: Tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager, has shown activity in previously treated small cell lung cancer (SCLC); however, real-world data on cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain limited. We evaluated the efficacy and safety of tarlatamab and laboratory findings associated with CRS in patients previously treated for extensive-stage SCLC.

Materials and methods: We retrospectively analyzed 11 patients who received tarlatamab through an expanded access program between October 2024 and May 2026. Repeated laboratory measurements were analyzed using generalized estimating equations and mixed-effects models.

Results: The objective response and disease control rates were 54.5% and 72.7%, respectively. The mean and median tumor size changes from baseline were -9.1% and -25.0%, respectively. The median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI]: 1.9-not reached) and 10.1 months (95% CI: 4.5-not reached), respectively. CRS occurred in seven patients (63.6%), with 10 events, all occurring during the first cycle and limited to Grade 1 or 2. No CRS event required tocilizumab treatment, intensive care unit admission, dose reduction, or treatment discontinuation. One patient developed Grade 3 ICANS and recovered fully. CRS events were associated with higher neutrophil percentages, lower lymphocyte percentages, and higher neutrophil-to-lymphocyte ratios than no-CRS events.

Conclusion: Tarlatamab shows encouraging antitumor activity and manageable toxicity in heavily pretreated Korean patients with SCLC. The neutrophil-to-lymphocyte ratio may represent an exploratory, concurrent hematologic correlate of CRS.