e20126 Background: Tarlatamab, a delta-like ligand 3 (DLL3)-directed bispecific T-cell engager, has revolutionized the treatment of small cell lung cancer (SCLC) since FDA approval in 2024. However, data are limited regarding the safety of tarlatamab with recent or concurrent CNS radiation therapy (RT) for brain metastases and how recent CNS RT may impact risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We describe CNS RT exposure relative to tarlatamab initiation and characterize associated toxicities. Methods: We conducted a retrospective chart review of patients with platinum-refractory SCLC and high-grade neuroendocrine carcinomas treated with tarlatamab between June 1, 2024, and June 1, 2025, at the University of Chicago Medical Center. Clinical data including demographics, performance status, disease characteristics, CNS RT history, and ICANS/CRS events were collected. Results: Twenty-four patients received tarlatamab during the study period (median age 64 years; 46% male; 75% White and 21% Black, median 2 lines of prior therapy range 1-4). Seven patients had brain metastases prior to tarlatamab initiation (four treated and three untreated with CNS RT). Overall, 13 of 24 patients (54%) developed CRS (n=5 grade 2 events), and 5 of 24 patients (21%) developed ICANS (n=1 grade 2 event). 3 of 7 patients (43%) with brain metastases developed CRS (n=1 grade 2 event) and 2 of 7 patients (29%) developed ICANS (n=1 grade 2). Eleven patients (46%) underwent CNS RT within 6 months of tarlatamab initiation (interval range: −6.0 to +5.5 months), including 4 patients who received CNS RT prior to tarlatamab initiation. Among patients who received CNS RT prior to tarlatamab, CRS occurred in 1 of 4 patients (25%) and ICANS in 2 of 4 patients (50%). No cases of radionecrosis were observed in patients treated with CNS RT during tarlatamab therapy. Conclusions: In this retrospective cohort, neither the presence of brain metastases nor treatment with CNS RT within six months of tarlatamab initiation was associated with clearly increased rates of CRS or ICANS. These real-world findings support the cautious use of tarlatamab in patients requiring CNS RT, with close monitoring. Larger studies are needed to further define the impact of RT timing on immune-related toxicities. Subgroup of patients receiving CNS RT within 6 months of tarlatamab treatment with CRS/ICANS events. Patient No. Duration of Tarlatamab Therapy (months) RT–Tarlatamab Interval (months) CRS Grade ICANS Grade 1 6.0 +2.1 months 1 none 2 4.0 +5.5 months 2 none 3 1.0 −2.0 months none none 4 5.7 −1.9 months 1 none 5 10.8 −4.0 months none 1 6 10.5 +0.7 months 2 none 7 1.9 +1.4 months none none 8* 9.5 +4.2 months 2 none 9 6.0 +0.5 months 1 none 10** 4.6 −6.0 months none 2 11 13.1 +2.5 months 2 none Majority of patients with SCLC. *Atypical carcinoid of the lung, transformed to SCLC. **Neuroendocrine tumor of the lung. </jats:table
Kaur et al. (Thu,) studied this question.