Applicability of the lung immune prognostic index (LIPI) in patients with metastatic solid tumors when treated with immune checkpoint inhibitors (ICI) in early clinical trials
Authors: A. Varga, A. Bernard-Tessier, E. Auclin, L. Mezquita Pérez, C. Baldini, D. Planchard, A. Marabelle, A. Hollebecque, B. Besse, C. Massard
Journal: Annals of Oncology (2019)

Background: Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/ (leucocytes-neutrophils) and lactate dehydrogenase (LDH) and is correlated with outcomes of patients treated with Immune Checkpoint Inhibitors (ICI) by tumor type. It has been shown for melanoma patients, NSCLC, SCLC, HNSCC, or TNBC but not in an all tumor type population. Methods: dNLR and LDH were retrospectively collected from 360 patients with metastatic disease treated since September 2015 to November 2017 at Gustave Roussy, in the Drug Development Department. LIPI portrays 3 groups: good group (GG) if dNLR< 3 and normal LDH, intermediate group (IG) if dNLR> 3 or LDH> upper limit of normal (ULN), and poor group (PG) if dNLR>3 and LDH>ULN. ICI benefit was analyzed according to overall survival (OS) and progression free survival (PFS). Results: From the 360 patients treated with ICI in early clinical trials, 353 (98%) were ICI naïve, 214 (59%) were male, 209 (58%) had a performance status of 1 with a median age at ICI treatment of 60 (range, 25-88), 322 (89%) received either a PD-1 or PD-L1 inhibitor and 268 (74%) as combination therapy. The most frequent tumor types were: NSCLC (14%), colorectal (14%), bladder (13%), renal (8%), breast (7%), HNSCC (7%) and cervix (6%). The median follow-up duration was of 14.1 months (m) [95%CI 12.9-16.1]. LIPI stratified the population into good group with 160 patients (44%), intermediate group with 161 patients (44%) and poor group with 39 patients (11%). The median OS was 17.8m [95%CI 13.1-not reached (NR)] vs. 11.68m [95%CI 8.8-15.3] vs. 3.9m [95%CI 2.1-6.4] for good, intermediate and poor group while the median PFS was of 4.6m [95%CI 4.0-6.2] for GG vs. 2.8m [95%CI 2.5-3.6] for IG vs. 1.4m [95%CI 1.2-2.0] for PG (both p < 0.0001). Conclusions: Poor LIPI score, combining dNLR>3 and LDH>ULN is associated with a poorer outcome in patients treated with ICI. Calculating LIPI prior starting ICI therapy can be useful in identifying patients that will not benefit from such a treatment choice. Legal entity responsible for the study: Drug Development Department, Gustave Roussy. Funding: Has not received any funding. Disclosure: A. Varga: Courses, trainings: Astra Zeneca, MSD, Roche; Travel funds: Boehringer Ingelheim, Clovis Oncology. L. Mezquita Pérez: Consulting, advisory role: Roche Diagnostics; Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, Accommodations, Expenses: Chugai. C. Baldini: Research Grants: Roche, Amgen, Pfizer, Abbvie, BMS; Travel and accommodation expenses: Roche, Amgen, Pfizer; Paid expert testimony: Abbvie, BMS. D. Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. A. Marabelle: Research Grants: Merus, BMS, Boehringer Ingelheim, Transgene; Member of Committee/Board: GSK, AstraZeneca, Oncovir, Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Bayer, Novartis, BMS, Symphogen, Genmab, Amgen, Biothera, Nektar, Pfizer, Seattle Genetics, Flexus Bio, Roche/Genentech, OSE immunotherapeutics, Transgene, Gritstone, Merck (MSD), Cerenis, Innate pharma, Protagen, Partner Therapeutics, Servier; Teaching/Speaker activities: Roche/Genentech, BMS, Merck (MSD), Merck Serono, Astra Zeneca/Medimmune, Amgen, Sanofi; Consulting: Roche, Pierre Fabre, Onxeo, EISAI, Bayer, Genticel, Rigontec, Daichii Sankyo, Imaxio, Sanofi, BioNTech, Corvus, GLG, Deerfield, Guidepoint Global, Edimark, SYSTEM ANALYTICS, imCheck, Sotio, Bioncotech. A. Hollebecque: Consultant/Advisory role: Amgen, Spectrum Pharmaceuticals, Lilly Travel and accommodation expenses: Servier, Amgen, Lilly; Courses, trainings: Bayer. C. Massard: Consultant/Advisory fees: Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, Novartis, Pfizer, Roche, Sanofi, Orion; Principal/sub-Investigator of Clinical Trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Zeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech, Inc., Gilead Sciences, Inc, Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, Hoffmann La Roche Ag, Incyte Corporation, Innate Pharma, Iris Servier, Janssen, Kura Oncology, Kyowa Kirin Pharm, Lilly, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Rigontec Gmbh, Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Inc, Tioma Therapeutics, Inc., Xencor; Research Grants: Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-financial support (drug supplied): AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. B. Besse: Sponsored Research at Gustave Roussy Cancer Center: Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. All other authors have declared no conflicts of interest.