Journal Article

844 Immune cell profile changes in patients treated with tarlatamab for extensive-stage small cell lung cancer in real world practice

Mansfield, Aaron, Schwecke, Anna, Luce Ailsa, Parikh Kaushal, Taylor, Skyler J, Smith, Katherine ER, Karam Dhauna, Shao Zuoyi, Shanshal Mohamed, Silva Corraes Andre de Menezes, Ma, Audrey, Syeda, Mina, Al-Ajmi, Abdullah, Dimou Anastasios, Wu, Chen, Regan, Kevin, Potter, Ashley, Leventakos Konstantinos, Lin, Yi, Antonious, Hazim, Molina, Julian

2025

Overview

BackgroundIn May 2024, the FDA approved tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager, for patients with extensive-stage small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy and at least one other prior line of therapy. We aim to examine the cellular immune cell profile changes seen in patients receiving this therapy in standard-of-care (SOC) practice.MethodsPatients who received tarlatamab at Mayo Clinic Rochester consented to research blood. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Excel and PRISM.ResultsThirteen patients with a median age 64 years (range 41-80) who were treated and evaluable for clinical response were included, 53% were women. All had a history of tobacco use.Nine (69%) patients had progressive disease (PD) after a median of 2 cycles, whereas 4 patients had partial response (PR) or stable disease (SD) after at least 2 cycles and remain on therapy (no-PD). Compared to the no-PD group, those whose disease PD early had higher levels of exhausted CD8 T cells at baseline (PD1+TIGIT+CD57+, PD vs no-PD, cells/µL: 17.4±5.6, 7.6±2.6, p=0.006). Interestingly, a CD8 TIGIT+PD1negCD57neg population was also identified which was higher at baseline (PD vs no-PD, cells/µL: 21.5±16.9, 12.2±5.33, p=0.039) and decreased significantly for the PD group from baseline to day 7 (21.5±16.9 to 9.30±10, p=0.039; figure 1A). This population was found to have a different functional profile than the exhausted phenotype in other solid tumors and its role in small cell lung cancer has not been defined. At day 7, compared to the no-PD group, the PD group also had a high level of B-cells (PD vs no-PD, cells/µL: 10.3±15, 4.07±1.83, p=0.027), classical monocytes (PD vs no-PD, cells/µL: 365±279, 226±121, p=0.035), and immunosuppressive monocytes (CD14+HLA-DRneg monocytes, cells/µL: 119±93, 33±42, p=0.05). In addition, the no-PD group had a statistically significant decrease from baseline to day 7 in intermediate monocytes (32.5±7.9 to 17±2.6, p=0.049; figure 1B).ConclusionsIn this study investigating the SOC outcomes of tarlatamab, early PD was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at SITC meeting.Abstract 844 Figure 1ACD8 T cell phenotype associated with clinical response[Image Omitted. See PDF.]Abstract 844 Figure 1BMonocyte phenotype associated with clinical response[Image Omitted. See PDF.]

• Publisher: BMJ Publishing Group LTD
• Subject: Genotype & phenotype / Lung cancer