184P Association of tumor-associated neutrophils (TAN) with immunotherapy outcomes in patients in advanced non-small cell lung cancer

Abstract

BackgroundNeutrophils are emerging as a potential biomarker related to the patient’s immune context, generally related to worse outcomes. The tumor-associated neutrophils (TAN) on the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) remains unknown. We aimed to determine TAN association with ICI outcomes in advanced NSCLC.MethodsMulticenter retrospective study of patients (pts) with advanced NSCLC treated with PD(L)-1 inhibitors between Feb.2014 and Sep.2021. Clinical and biological data were collected from medical reports. Stromal TAN density was analyzed by morphology on hematoxylin/eosin slides: quantitatively (0-100%) and semi-quantitatively (0, 1+, 2+, 3+); high TAN density was defined as >2+ based on our previous work (Mezquita et al, WCLC 2019). We also assessed by morphology other immune cells on the TME, including tumor-infiltrating lymphocytes. The primary endpoint was progression-free survival (PFS) and overall survival (OS).ResultsA total of 170 pts have been enrolled to date; 71% were male, 92% smokers with median age of 64 years and 71% had performance status ≤1; 76% had non-squamous histology with PD-L1 ≥1% in 79% (unknown in 60 cases). Median number of previous lines was 1 (0-11). The presence of TAN was observed in 26% of cases (N=44), with high-TAN in 4% (N=6). TAN was more likely detected in ≥65 years-old pts (64% vs. 37%; p=0.002) and PD-L1 negative tumors (63% vs. 24%; <0.0001). No differences on TAN were observed according to smoking or histology. The median PFS was 2.9 months (mo.) (95% CI 2.3-4.3). The presence of TAN was significantly associated with a poor PFS: 1.41 mo. (0.69-not reached) for high-TAN vs. 2.99 mo. (2.2-4.4) for low-TAN (p=0.007). The correlation with other immune cells on the TME and the multivariate analysis on the TME will be presented in the meeting. OS data was not mature yet.ConclusionsWe report preliminary data of a potential detrimental impact of the presence of TAN on ICI outcomes (PFS) in patients with advanced NSCLC, suggesting that TAN could play a role as an immune-resistant mechanism. This cohort is still ongoing and updated data will be reported in the meeting.Legal entity responsible for the studyLaura Mezquita.FundingHas not received any funding.DisclosureT. Gorría Puga: Financial Interests, Personal, Other, expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, expenses: Hibor. E. Auclin: Financial Interests, Personal, Other, travel expenses: Mundipharma; Financial Interests, Personal, Other, lectures and educational activities: Sanofi Genzymes. D. Planchard: Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research; travel and accommodation expenses: AstraZeneca; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research: Boehringer; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research: Ingelheim; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria: Celgene; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; roles in clinical trials research: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research: Eli Lilly; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research: Merck; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research; travel and accommodation expenses: Novartis; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research; travel and accommodation expenses: Pfizer; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; travel and accommodation expenses: prIME Oncology; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria: Peer CME; Financial Interests, Personal, Other, Consulting, advisory roles or lectures; honoraria; roles in clinical trials research; travel and accommodation expenses: Roche; Financial Interests, Personal, Other, roles in clinical trials research: Medimmune; Financial Interests, Personal, Other, roles in clinical trials research: Sanofi-Aventis; Financial Interests, Personal, Other, roles in clinical trials research: Taiho Pharma; Financial Interests, Personal, Other, roles in clinical trials research: Novocure. J. Adam: Financial Interests, Personal, Other, Advisory board roles: AstraZeneca; Financial Interests, Personal, Other, Advisory board roles: Bayer; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Other, honoraria: Bristol Myers Squibb. B. Besse: Financial Interests, Personal, Other, Sponsored research sponsorship: Gustave Roussy Cancer Center; Financial Interests, Personal, Other, Sponsored research sponsorship: AbbVie; Financial Interests, Personal, Other, Sponsored research sponsorship: Amgen; Financial Interests, Personal, Other, Sponsored research sponsorship: AstraZeneca; Financial Interests, Personal, Other, Sponsored research sponsorship: Biogen; Financial Interests, Personal, Other, Sponsored research sponsorship: Blueprint Medicines; Financial Interests, Personal, Other, Sponsored research sponsorship: Bristol Myers Squibb; Financial Interests, Personal, Other, Sponsored research sponsorship: Celgene; Financial Interests, Personal, Other, Sponsored research sponsorship: Eli Lilly; Financial Interests, Personal, Other, Sponsored research sponsorship: GSK; Financial Interests, Personal, Other, Sponsored research sponsorship: Ignyta; Financial Interests, Personal, Other, Sponsored research sponsorship: IPSEN; Financial Interests, Personal, Other, Sponsored research sponsorship: Merck; Financial Interests, Personal, Other, Sponsored research sponsorship: MSD; Financial Interests, Personal, Other, Sponsored research sponsorship: Nektar; Financial Interests, Personal, Other, Sponsored research sponsorship: Onxeo; Financial Interests, Personal, Other, Sponsored research sponsorship: Pfizer; Financial Interests, Personal, Other, Sponsored research sponsorship: Pharma mar; Financial Interests, Personal, Other, Sponsored research sponsorship: Sanofi; Financial Interests, Personal, Other, Sponsored research sponsorship: Spectrum Pharmaceuticals; Financial Interests, Personal, Other, Sponsored research sponsorship: Takeda; Financial Interests, Personal, Other, Sponsored research sponsorship: Tiziana Pharma. L. Mezquita: Financial Interests, Personal, Other, Sponsored Research: Amgen; Financial Interests, Personal, Other, Sponsored Research; Travel, Accommodations, Expenses; Lectures and educational activities: Bristol-Myers Squibb; Financial Interests, Personal, Other, Sponsored Research: Boehringer; Financial Interests, Personal, Other, Sponsored Research: Ingelheim; Financial Interests, Personal, Other, Sponsored Research: Stilla; Financial Interests, Personal, Other, Sponsored Research: Inivata; Financial Interests, Personal, Other, Consulting, advisory role: Roche Diagnostics; Financial Interests, Personal, Other, Consulting, advisory role; Lectures and educational activities: Takeda; Financial Interests, Personal, Other, Consulting, advisory role; Lectures and educational activities; Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Other, Lectures and educational activities: Tecnofarma; Financial Interests, Personal, Other, Mentorship program with key opinion leaders: AstraZeneca. All other authors have declared no conflicts of interest. BackgroundNeutrophils are emerging as a potential biomarker related to the patient’s immune context, generally related to worse outcomes. The tumor-associated neutrophils (TAN) on the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) remains unknown. We aimed to determine TAN association with ICI outcomes in advanced NSCLC. Neutrophils are emerging as a potential biomarker related to the patient’s immune context, generally related to worse outcomes. The tumor-associated neutrophils (TAN) on the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) remains unknown. We aimed to determine TAN association with ICI outcomes in advanced NSCLC. MethodsMulticenter retrospective study of patients (pts) with advanced NSCLC treated with PD(L)-1 inhibitors between Feb.2014 and Sep.2021. Clinical and biological data were collected from medical reports. Stromal TAN density was analyzed by morphology on hematoxylin/eosin slides: quantitatively (0-100%) and semi-quantitatively (0, 1+, 2+, 3+); high TAN density was defined as >2+ based on our previous work (Mezquita et al, WCLC 2019). We also assessed by morphology other immune cells on the TME, including tumor-infiltrating lymphocytes. The primary endpoint was progression-free survival (PFS) and overall survival (OS). Multicenter retrospective study of patients (pts) with advanced NSCLC treated with PD(L)-1 inhibitors between Feb.2014 and Sep.2021. Clinical and biological data were collected from medical reports. Stromal TAN density was analyzed by morphology on hematoxylin/eosin slides: quantitatively (0-100%) and semi-quantitatively (0, 1+, 2+, 3+); high TAN density was defined as >2+ based on our previous work (Mezquita et al, WCLC 2019). We also assessed by morphology other immune cells on the TME, including tumor-infiltrating lymphocytes. The primary endpoint was progression-free survival (PFS) and overall survival (OS). ResultsA total of 170 pts have been enrolled to date; 71% were male, 92% smokers with median age of 64 years and 71% had performance status ≤1; 76% had non-squamous histology with PD-L1 ≥1% in 79% (unknown in 60 cases). Median number of previous lines was 1 (0-11). The presence of TAN was observed in 26% of cases (N=44), with high-TAN in 4% (N=6). TAN was more likely detected in ≥65 years-old pts (64% vs. 37%; p=0.002) and PD-L1 negative tumors (63% vs. 24%; <0.0001). No differences on TAN were observed according to smoking or histology. The median PFS was 2.9 months (mo.) (95% CI 2.3-4.3). The presence of TAN was significantly associated with a poor PFS: 1.41 mo. (0.69-not reached) for high-TAN vs. 2.99 mo. (2.2-4.4) for low-TAN (p=0.007). The correlation with other immune cells on the TME and the multivariate analysis on the TME will be presented in the meeting. OS data was not mature yet. A total of 170 pts have been enrolled to date; 71% were male, 92% smokers with median age of 64 years and 71% had performance status ≤1; 76% had non-squamous histology with PD-L1 ≥1% in 79% (unknown in 60 cases). Median number of previous lines was 1 (0-11). The presence of TAN was observed in 26% of cases (N=44), with high-TAN in 4% (N=6). TAN was more likely detected in ≥65 years-old pts (64% vs. 37%; p=0.002) and PD-L1 negative tumors (63% vs. 24%; <0.0001). No differences on TAN were observed according to smoking or histology. The median PFS was 2.9 months (mo.) (95% CI 2.3-4.3). The presence of TAN was significantly associated with a poor PFS: 1.41 mo. (0.69-not reached) for high-TAN vs. 2.99 mo. (2.2-4.4) for low-TAN (p=0.007). The correlation with other immune cells on the TME and the multivariate analysis on the TME will be presented in the meeting. OS data was not mature yet. ConclusionsWe report preliminary data of a potential detrimental impact of the presence of TAN on ICI outcomes (PFS) in patients with advanced NSCLC, suggesting that TAN could play a role as an immune-resistant mechanism. This cohort is still ongoing and updated data will be reported in the meeting. We report preliminary data of a potential detrimental impact of the presence of TAN on ICI outcomes (PFS) in patients with advanced NSCLC, suggesting that TAN could play a role as an immune-resistant mechanism. This cohort is still ongoing and updated data will be reported in the meeting.