Analysis of corticosteroid exposure on efficacy of tarlatamab in small cell lung cancer: A multicenter retrospective study.

Abstract

8088 Background: Tarlatamab, a delta-like ligand 3 (DLL3)-targeted bispecific T-cell engager, has shown meaningful activity in small cell lung cancer (SCLC). Immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common with T-cell–redirecting therapies and frequently require corticosteroids or cytokine-directed agents like tocilizumab. The impact of lymphodepleting corticosteroid exposure on tarlatamab efficacy remains unclear. Methods: We performed a retrospective analysis of patients with SCLC treated with tarlatamab from 2018–2025 across the University of Kansas and nine cancer centers included in the DLL3 PanTUMOR database. The primary endpoint was progression-free survival (PFS) stratified by cumulative dexamethasone dose. Other endpoints included overall response rate (ORR), characterization of CRS and ICANS, and overall survival (OS). A cost analysis of dexamethasone versus tocilizumab was also conducted. Results: Among 143 tarlatamab-treated patients, dexamethasone use for CRS or ICANS did not reduce PFS or ORR compared with patients not receiving corticosteroids. Tocilizumab did not reduce steroid needs. Median dexamethasone dose was higher in patients treated with tocilizumab. Severe CRS/ICANS was associated with significantly shorter OS. Cost analysis demonstrates the significant cost savings using dexamethasone compared to tocilizumab for treatment of immune-mediated toxicities. Conclusions: Corticosteroid exposure did not compromise tarlatamab efficacy, supporting optimized toxicity management without diminishing antitumor activity of DLL3-targeted T-cell–redirecting therapies. Endpoints Total Number of Evaluable Patients Outcomes Median PFS of tarlatamab with cumulative steroid dose Arm 1: No dexArm 2: 1-40 mg of dexArm 3: 41+ mg of dex Arm 1: 66Arm 2: 42Arm 3: 16 Arm 1: 2.53 moArm 2: 4.70 moArm 3: 3.68 moHR=1.0295% CI: 0.73-1.42 p=0.31 ORR of tarlatamab with cumulative steroid doseArm 1: No dexArm 2: 1-40 mg of dexArm 3: 41+ mg of dex Arm 1: 55Arm 2: 34Arm 3: 11 Arm 1: 29.1%Arm 2: 47.1% Arm 3: 36.4% Comparison of ORR with CRS (any grade) versus without CRS CRS: 58No CRS: 60 CRS: 34.5%No CRS: 33.3% Comparison of ORR with ICANS (any grade) versus without ICANS ICANS: 33No ICANS: 85 ICANS: 36.4%No ICANS: 32.9% Did the use of tocilizumab result in lower cumulative steroid use No tocilizumab: 42Tocilizumab: 28 Median dex dose without tocilizumab: 10 mgMedian dex dose with tocilizumab: 35 mg Median OS with grade 3+ CRS or ICANS versus with grade 0-2 CRS/ICANS Grade 0-2: 133Grade 3+: 10 Grade 0-2: 11.37 moGrade 3+: 4.19 moHR=0.3495% CI: 0.15-0.76p=0.006 Cost analysis for dex versus tocilizumabAverage wholesale price: tocilizumab $165,724, $3.13 dex10 mg CRS: 7237 doses of tocilizumab 37 doses of tocilizumab substituted with 37 dex 10 mg doses would have saved $173,962