Practical Management of Adverse Events in Patients Receiving Tarlatamab, a DLL3-targeted Bispecific T-cell Engager Immunotherapy, for Previously Treated Small Cell Lung Cancer

Abstract Tarlatamab is a bispecific T-cell engager (BiTE ® ) immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer (SCLC), tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial showed that the most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; 53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and anemia (30%). CRS was mostly grade 1 or 2 in severity, occurred primarily after the first or second tarlatamab dose, and was managed with supportive care, which included administration of antipyretics (e.g., acetaminophen), intravenous hydration and/or glucocorticoids. Other TEAEs of interest included neutropenia (16%) and immune-effector cell-associated neurotoxicity syndrome and associated neurologic events (10%). Given that tarlatamab is the first T-cell engager approved for the treatment of SCLC, raising awareness regarding the monitoring and management of tarlatamab-associated adverse events is essential. Here, we describe the timing, occurrence, and duration of these AEs and review the management and risk mitigation strategies used by clinical investigators during the DeLLphi-301 trial.