Safety, Efficacy, and Central Nervous System Control in Patients with High Baseline Risk Factors Treated with Tarlatamab for SCLC or Extrapulmonary Small Cell Carcinoma

Introduction: SCLC remains the most aggressive lung cancer with a poor prognosis. Tarlatamab, a bispecific T-cell engager, is approved for use in extensive-stage SCLC after progression on a platinum-based chemotherapy on the basis of the DeLLphi-301 trial. Because of the restrictive inclusion criteria of this trial, substantial gaps remain in our understanding of treatment for many patients. Methods: We performed a retrospective chart review of patients who were treated with tarlatamab at the University of Kansas Cancer Center from May 2024 through December 2024 for SCLC (cohort 1) or extrapulmonary small cell carcinoma (EPSCC) (cohort 2). Patients were included if they received at least one dose of tarlatamab regardless of baseline characteristics. Results: A total of 21 patients were included in cohort 1, and three patients were included in cohort 2. In the SCLC cohort, 14 patients (66.6%) had central nervous system (CNS) involvement, five patients (23.8%) required baseline oxygen, and five patients (23.8%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or greater. There were 13 patients (61.9%) who developed cytokine release syndrome (CRS), with grade 3 or higher CRS noted in two patients (15.3%). There were 10 patients (47.6%) who developed immune effector cell-associated neurotoxicity syndrome (ICANS), with three patients (14.2%) developing grade 3 or higher ICANS. In the three patients with extrapulmonary small cell carcinoma, any-grade CRS occurred in two patients (66.7%), and grade 1 ICANS occurred in one patient (33.3%). Characteristics such as ECOG of 2 or higher, baseline oxygen use, and untreated CNS metastases are associated with high rates of CRS and ICANS. In 17 patients evaluable for best response in cohort 1, partial response was seen in six (35.2%) patients. No patients in cohort 2 had disease assessment performed at the time of data cutoff. Alternative CNS disease control using tarlatamab alone or with concurrent radiation provided clinical benefit to three patients. Conclusions: Baseline risk factors such as oxygen dependence, poor ECOG performance status, bulky disease, and untreated CNS involvement may increase CRS and ICANS rates after tarlatamab. However, subsequent doses exhibited a more favorable safety profile, supporting outpatient administration and reduced observation time. CNS management strategies, including concurrent radiation or monotherapy with tarlatamab, exhibited promising efficacy. These findings highlight the need for further research into CRS and ICANS risk stratification, optimal CNS management, and efficacy in extrapulmonary small cell carcinoma through larger studies.