3586 - Extrathoracic Disease Volume as a Risk Factor for Cytokine Release Syndrome in Patients with Small Cell Lung Cancer Treated with Tarlatamab
Presenter(s)
B. R. Perez1, D. Huang1, H. Kaur2, A. Esposito2, S. Sindhwani3, C. M. Bestvina3, E. E. Vokes3, M. Garassino3, N. Choudhury3, and A. Juloori1; 1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, 2University of Chicago Medical Center, Chicago, IL, 3Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
Purpose/Objective(s): Tarlatamab, a bispecific T-cell engager (BiTE) targeting DLL3, has demonstrated efficacy in small cell lung cancer (SCLC) but is associated with cytokine release syndrome (CRS) in roughly half of patients. We sought to determine whether pre-treatment disease volume and anatomic distribution are associated with CRS risk in tarlatamab-treated SCLC patients.
Materials/Methods: We performed a single-institution retrospective analysis of 24 patients with SCLC who initiated tarlatamab between July 2024 and May 2025. Pre-treatment disease volumes were contoured in Eclipse using diagnostic scans (PET or CT of the chest, abdomen, and pelvis +/- MRI brain) obtained within three months prior to tarlatamab initiation. Disease volumes were categorized as intrathoracic or extrathoracic. Fisher’s exact test was used to compare CRS rates by disease location. Univariable and multivariable Cox proportional hazards models were used to identify predictors of CRS.
Results: The cohort included 24 patients (54% female). Median prior lines of therapy was 2 (IQR 1-2). By disease location, 6 (25%) had intrathoracic disease only, 5 (21%) extrathoracic only, and 13 (54%) both. Median total disease volume was 75.3 cc (IQR 39.3-146.0), and median extrathoracic volume was 9.8 cc (IQR 2.2-50.3). Across all patients, 11 of 24 patients (45.8%) developed CRS at a median of 1 day after treatment initiation (IQR 0-15). All CRS events were grade 1 or 2, with no grade 3 or higher events. CRS rates differed significantly by disease location: 5/5 (100%) of patients with extrathoracic-only disease developed CRS compared to 5/13 (38%) with both and 1/6 (17%) with intrathoracic-only disease (p = 0.015). On univariable analysis, extrathoracic disease volume was significantly associated with CRS (HR 1.12 per 100 cc, 95% CI 1.02-1.24, p = 0.024). On multivariable analysis adjusting for prior lines of therapy and ECOG performance status, extrathoracic volume remained independently significant (adjusted HR 1.16 per 100 cc, 95% CI 1.04-1.29, p = 0.009).
Conclusion: In this retrospective cohort, greater extrathoracic disease volume was independently associated with increased CRS risk among tarlatamab-treated SCLC patients. Pre-treatment extrathoracic volume on staging imaging may identify patients who warrant enhanced monitoring, including inpatient observation during initial dosing and a lower threshold for tocilizumab administration. These findings could also suggest that cytoreductive radiation therapy targeting bulky extrathoracic disease prior to tarlatamab initiation could mitigate CRS risk.