Tumour-infiltrating lymphocyte density is associated with favourable outcome in patients with advanced non–small cell lung cancer treated with immunotherapy

Ithar Gataa, Laura Mezquita, Caroline Rossoni, Edouard Auclin, Myriam Kossai, Frank Aboubakar, Sylvestre Le Moulec, Julie Massé, Morgane Masson, Nina Radosevic-Robin, Pierre Alemany, Mathieu Rouanne, Virginia Bluthgen, Lizza Hendriks, Caroline Caramella, Anas Gazzah, David Planchard, Jean Pierre Pignon, Benjamin Besse, Julien Adam

    Research output: Contribution to journalArticlepeer-review

    57 Citations (Scopus)

    Abstract

    Background: The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. Methods: This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). Results: Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28–0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25–0.64). Median PFS was 13.0 months (95% CI: 5.0–not reached) with high-TIL versus 2.2 months (95% CI: 1.7–3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2–not reached) versus 8.4 months (95% CI: 5.0–11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P <.0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9–6.7) and 11.7 months (95% CI: 9.3–13.0), respectively, with no association with TILs. Conclusions: High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy.

    Original languageEnglish
    Pages (from-to)221-229
    Number of pages9
    JournalEuropean Journal of Cancer
    Volume145
    DOIs
    Publication statusPublished - 1 Mar 2021

    Keywords

    • Biomarkers
    • Immune checkpoint inhibitor
    • Immunotherapy
    • Lung cancer
    • NSCLC
    • Nivolumab
    • Non–small cell lung cancer
    • Prognostic
    • TIL
    • Tumor-infiltrating lymphocytes

    Cite this