BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.
- Mountzios, G.
- Samantas, E.
- Senghas, K.
- Zervas, E.
- Krisam, J.
- Samitas, K.
- Bozorgmehr, F.
- Kuon, J.
- Agelaki, S.
- Baka, S.
- Athanasiadis, I.
- Gaissmaier, L.
- Elshiaty, M.
- Daniello, L.
- Christopoulou, A.
- Pentheroudakis, G.
- Lianos, E.
- Linardou, H.
- Kriegsmann, K.
- Kosmidis, P.
- El Shafie, R.
- Kriegsmann, M.
- Psyrri, A.
- Andreadis, C.
- Fountzilas, E.
- Heussel, C. P.
- Herth, F. J.
- Winter, H.
- Emmanouilides, C.
- Oikonomopoulos, G.
- Meister, M.
- Muley, T.
- Bischoff, H.
- Saridaki, Z.
- Razis, E.
- Perdikouri, E. I.
- Stenzinger, A.
- Boukovinas, I.
- Reck, M.
- Syrigos, K.
- Thomas, M.
- Christopoulos, P.
Keywords
- Pd-l1
- advanced lung cancer inflammation index
- immunotherapy
- neutrophil-to-lymphocyte ratio
- non-small-cell lung cancer
- Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Takeda, Pfizer, Amgen, and Merck
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