Optimizing Tarlatamab Delivery in Small Cell and Neuroendocrine Lung Cancer: Real-World Insights into Step-Up Dosing...

Tarlatamab, a DLL3-targeted bispecific T-cell engager, has emerged as a second-line therapy for extensive-stage small cell lung cancer (ES-SCLC) following progression on platinum-based chemoimmunotherapy. While clinical trials have demonstrated promising efficacy, real-world data on safety remain limited.

This retrospective study included 40 patients with SCLC or high-grade neuroendocrine carcinoma treated with tarlatamab at Moffitt Cancer Center between May 2024 and February 2025. Clinical, laboratory, and treatment-related variables including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reviewed. Predictive models for these toxicities were developed using Firth logistic regression based on data from 30 patients who did not receive prophylactic tocilizumab.

The median age was 66.5 years; 55% were male, and 87.5% had an ECOG performance status of 0 to 1. Among patients who did not receive prophylactic tocilizumab (N = 30), 53.3% developed CRS and 23.3% developed ICANS after Cycle 1 Day 1, with 10% experiencing grade ≥ 3 severity for each. Three patients discontinued treatment due to severe CRS/ICANS, with 2 deaths and 1 transition to hospice. Among those who received prophylactic tocilizumab (N = 10), 1 patient developed grade 2 CRS and none developed ICANS. Elevated LDH and liver metastasis were independent predictors of CRS; LDH was also predictive of grade ≥ 2 CRS. Diabetes and cardiovascular disease were independently associated with ICANS.

Tarlatamab is associated with higher CRS and ICANS rates in real-world settings than observed in trials. Prophylactic tocilizumab may mitigate these toxicities in high-risk patients and should be considered for incorporation into treatment protocols.