Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer

Abstract

Tarlatamab is a bispecific T-cell engager 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, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%). Cytokine release syndrome 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 the administration of antipyretics (e.g., acetaminophen), intravenous hydration, and/or glucocorticoids. Other treatment-emergent adverse effects 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 small cell lung cancer, raising awareness with regard to the monitoring and management of tarlatamab-associated adverse events is essential. Here, the authors describe the timing, occurrence, and duration of these adverse events and review the management and risk-mitigation strategies used by clinical investigators during the DeLLphi-301 trial.

Keywords: DeLLphi‐301; adverse event management; safety profile; tarlatamab.

FIGURE 1

Time of adverse event onset from the first tarlatamab dose. Violin box plot showing the time to onset of some of the most common treatment‐emergent adverse events from the first dose of tarlatamab in the DeLLphi‐301 trial. The median time to onset and the interquartile range are indicated within each plot, with the breadth of the violin box plot indicating the patient distribution at any particular time point and the height proportional to the incidence rate of each event. The x‐axis has a variable scale. CRS indicates cytokine release syndrome; ICANS, immune effector cell‐associated neurotoxicity syndrome and associated neurologic events.

FIGURE 2

The incidence of CRS and ICANS by cycle and grade. The incidence of CRS and ICANS according to severity and treatment cycle are shown for patients in the 10‐mg tarlatamab dose cohort. During the first cycle, CRS was reported by 54 of 133 patients (41%) after the first tarlatamab dose (days 1–7), by 39 of 133 patients (29%) after the day‐8 dose (days 8–14), and by 10 of 133 patients (8%) after the day‐15 dose (days 15–28). CRS events were identified on the basis of a narrow search for preferred terms in MedDRA version 26.1 and were graded according to the American Society for Transplantation and Cellular Therapy 2019 consensus criteria. During the first cycle, ICANS was reported in one of 133 patients (<1%) after the first tarlatamab dose (days 1–7), in three of 133 patients (2%) after the day‐8 dose (days 8–14), and in three of 133 patients (2%) after the day‐15 dose (days 15–28). ICANS data include associated neurologic events identified on the basis of a broad search for 61 preferred terms in MedDRA. CRS indicates cytokine release syndrome; ICANS, immune effector cell‐associated neurotoxicity syndrome and associated neurologic events; MedDRA, Medical Dictionary for Regulatory Activities.

FIGURE 3

Common and adverse events of interest in the DeLLphi‐301 trial. ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; CRS, cytokine release syndrome; ICANS, immune effector cell‐associated neurotoxicity syndrome and associated neurologic events; IQR, interquartile range; IV, intravenous; LFTs, liver function tests.