Abstract 1057P
Background
HPD has been described in ≃14-26% of pretreated NSCLC pts upon single-agent (SA) ICI and has not been reported upon PCT-ICI. So far, no predictive biomarkers are available for HPD early detection.
Methods
NSCLC pts treated with 1st line SA-ICI or PCT-ICI were assessed for HPD and circulating neutrophils. HPD required 3 radiological scans and was defined as delta tumor growth rate (TGR) [TGR upon ICI – TGR prior ICI) >50% and/or TGR ratio (TGR upon ICI/ TGR prior ICI) ≥2. Circulating low density neutrophils (LDNs) were assessed by flow cytometry on peripheral blood mononuclear cells (PMBCs). LDNs were defined as CD66b+CD15+ cells among CD11b+ PBMCs and immature subtypes as % of CD10- LDNs. The association between LDNs and outcome and the LDNs predictive role were assessed by non parametric and penalized model-based tests. The LDNs’ sensitivity to cisplatin induced cell death were tested in-vitro.
Results
141 NSCLC pts were included: 75 treated with SA-ICI and 66 with PCT-ICI. In the SA-ICI cohort, PD and HPD occurred in 31 (41%) and 6 (8%) pts. CD10- LDNs were significantly higher (p=0.011) in HPD [median (Me): 43.55, interquartile range (IQR): 46.5] vs PD [Me: 9.44, IQR: 15.44]. CD10- LDNs were associated with HPD [odds ratio (OR): 2.88, 90% CI: 1.61; 5.16] showing a good HPD prediction capability [cross-validated ROC AUC: 0.77, 90% CI: 0.51;1.00]. A 29.5% cut-off value was identified by Youden index to discriminate HPD from others. In the PCT-ICI cohort, 10 pts had CD10- LDNs >29.5% being at high HPD risk, however none of them experienced it. In 5 of these 10 HPD high-risk pts with available dynamic LDNs evaluation upon PCT-ICI, a 52.2% decrease in median CD10- LDNs occurred, while in 6 pts with HPD upon SA-ICI, only a 2.8% decrease was observed, suggesting that PCT prevents HPD by reducing immature CD10- LDNs. In vitro experiments also showed that cisplatin increased necrotic cell death preferentially among immature CD10- LDNs vs mature CD10+ LDNs.
Conclusions
Baseline % of immature CD10- LDNs is a simple cost-effective HPD predictor upon 1st line SA-ICI and could select NSCLC pts to be addressed to PCT-ICI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
International Association for the Study of Lung Cancer (IASLC) Young Investigator Award.
Disclosure
R. Ferrara: Financial Interests, Personal, Advisory Board, In June 2019: MSD; Financial Interests, Institutional, Invited Speaker: MSD, Pfizer, AstraZeneca, Roche, Sanofi, Novartis, BMS, Ipsen, Daiichi Sankyo Company. G. Lo Russo: Financial Interests, Personal, Other: BMS, MSD, Italfarmaco, Novartis, Roche, AstraZeneca, Sanofi, Pfizer. C. Proto: Financial Interests, Personal, Advisory Board: MSD, Roche, AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: MSD, Roche, BMS, AstraZeneca; Financial Interests, Institutional, Principal Investigator: Janssen, Pfizer, Lilly, Spectrum, Roche, MSD, BMS, AstraZeneca. A. Prelaj: Financial Interests, Personal, Other: BMS, Roche, AstraZeneca. F.G.M. De Braud: Financial Interests, Personal, Advisory Board: Ignyta, BMS, Daiichi Sankyo, Pfizer, Octimet Oncology, Incyte, Teofarma, Pierre Fabre, Roche, EMD Serono, Sanofi, NMS Nerviamo Medical Science; Financial Interests, Personal, Speaker’s Bureau: BMS, Roche, Ignyta, Bayer, Accmed Dephaforum, Nadirex, Merck, Biotechspert, Prime Oncology, Pfizer, Servier, Celgene, Tesaro, Loxo Oncology, Sanofi, Healthcare Research and Pharmacoepidemiology; Financial Interests, Institutional, Principal Investigator: Novartis, Janssen, Roche, BMS, Celgene, Incyte, NMS, Merck KGAA, Kymab, Pfizer, Tesaro. M.C. Garassino: Financial Interests, Personal, Other: AstraZeneca, BMS, MSD, International GmbH, Boehringer, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda. All other authors have declared no conflicts of interest.