Tumor microenvironment associated with increased pretreatment density of activated PD-1+ LAG-3+/− TIM-3− CD8+ T cells facilitates clinical response to axicabtagene ciloleucel (axi-cel) in patients (pts) with large B-cell lymphoma.

Authors

null

Jerome Galon

HalioDx, Marseille, France

Jerome Galon , Nathalie Scholler , Regis Perbost , Sarah Turcan , Corinne Danan , Frederick Lundry Locke , Sattva Swarup Neelapu , David Bernard Miklos , Caron A. Jacobson , Lazaros J. Lekakis , Yi Lin , Armin Ghobadi , Justin Chou , Zixing Wang , Allen Xue , John M. Rossi , Adrian Bot

Organizations

HalioDx, Marseille, France, Kite, a Gilead Company, Santa Monica, CA, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, MD Anderson Cancer Center, Houston, TX, Stanford University School of Medicine, Stanford, CA, Dana-Farber Cancer Institute, Boston, MA, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, Mayo Clinic, Rochester, MN, Washington University School of Medicine, St Louis, MO

Research Funding

Pharmaceutical/Biotech Company
Kite, a Gilead Company

Background: Axi-cel is a US and EU-approved autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy for pts with relapsed/refractory large B cell lymphoma after ≥ 2 prior therapies. In ZUMA-1 (NCT02348216), the objective response rate was 83% (58% complete response rate; Locke et al. Lancet Oncol. 2019). T cell-related biology (Immunosign 21; Immunoscore) measured pretreatment in the tumor microenvironment (TME) was associated with response to axi-cel (Rossi et al. AACR 2018. #LB-016; Rossi et al. AACR 2019. #CT153). This expanded analysis characterized the pretreatment TME immune contexture and examined associations between immune cell subsets and response. Methods: In ZUMA-1, pts received axi-cel at a target dose of 2.0 × 106 CAR T cells/kg. Archival pretreatment tumor biopsy samples were analyzed by multiplex immunohistochemistry (Brightplex). Two panels were developed and applied to assess T cell (CD3, CD8, FoxP3, PD-1, LAG-3, TIM-3) and myeloid cell (CD11b, CD14, CD15, LOX1, S100A9, CD68) subsets (n = 14 total). The association between T cell and myeloid cell subset density, prespecified immune scores (Immunosign 21; Immunoscore), and objective response was evaluated. T test values were based on Brightplex analysis. Results: Pretreatment tumor biopsy samples from 18 pts were analyzed (14 objective responders and 4 nonresponders). The pretreatment TME comprised all major myeloid and T cell subsets, with diverse distribution across samples analyzed. The median TME density of monocytes (CD11b+ CD15− CD14+; 1215 cells/mm2) and macrophages (CD68+; 530 cells/mm2) was greater than that of the total CD8+ T cell subset (312 cells/mm2). The pretreatment Immunosign 21 and Immunoscore scores associated positively with the density of all major T cell subsets and some myeloid subsets. The density of activated CD8+ T cells (PD-1+ LAG-3+/− TIM-3−) was most significantly associated with clinical response versus other T cell subsets. The density of nonactivated CD8+ T cells (PD-1− LAG-3− TIM-3−) and exhausted CD8+ T cells (PD-1+ LAG-3+ TIM-3+) were not significantly associated with response. Additional characterization of the immune contexture and correlative analysis of cell subsets will be presented. Conclusions: These results suggest that a TME associated with increased density of activated PD-1+ LAG-3+/− TIM-3− CD8+ T cells, measurable pretreatment, facilitates clinical response in pts post–axi-cel.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Cellular Immmunotherapy

Citation

J Clin Oncol 38: 2020 (suppl; abstr 3022)

DOI

10.1200/JCO.2020.38.15_suppl.3022

Abstract #

3022

Poster Bd #

86

Abstract Disclosures