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

Cancer. 2025 Feb 1;131(3):e35738. doi: 10.1002/cncr.35738.

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.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific* / administration & dosage
  • Antibodies, Bispecific* / adverse effects
  • Antibodies, Bispecific* / therapeutic use
  • Cytokine Release Syndrome / chemically induced
  • Humans
  • Immunotherapy* / adverse effects
  • Immunotherapy* / methods
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Membrane Proteins* / antagonists & inhibitors
  • Membrane Proteins* / immunology
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology

Substances

  • Antibodies, Bispecific
  • Membrane Proteins