Flare Reaction following Tarlatamab Treatment in a Patient with Extensive-Stage Small Cell Lung Cancer: Case Report.

Introduction: Tarlatamab is a bispecific T-cell engager (BiTE) targeting DLL3 and shows promising efficacy in relapsed small cell lung cancer (SCLC). Although flare reactions are recognized with immune checkpoint inhibitors, reports in patients receiving tarlatamab remain limited. Case Presentation: We describe the case of a 74-year-old woman with extensive-stage SCLC who developed acute radiological worsening within 4 days after initiating third-line tarlatamab therapy, followed by rapid improvement by day 8. Chest computed tomography performed 1 week prior to treatment and on day 1 revealed no significant changes in the right hilar mass size (56.5 mm vs. 54.0 mm) or the right lower lobe infiltrating shadow (82.5 mm vs. 82.0 mm). On day 4, the right hilar mass and lower lobe lesion increased to 68.0 mm and 74.1 mm, respectively, along with surrounding ground-glass opacity and pleural effusion. By day 8, these lesions had decreased to 56.3 mm and 73.8 mm, respectively, and were further reduced by day 15 to 54.1 mm and 73.3 mm, respectively, with complete resolution of pleural effusion. Cytokine release syndrome (grade 1-2) was noted with tarlatamab administration on days 1, 8, and 15. Based on the temporal association, imaging findings, and clinical course, the event was considered flare reaction rather than natural tumor progression. Conclusion: Our findings suggest that flare reaction occurs within days of initiating tarlatamab, possibly attributable to acute immune activation, as reported in BiTE therapies. Awareness of this possibility may help avoid premature discontinuation of effective treatment.