# Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer

## TL;DR

A new biomarker called ALI can predict better outcomes for lung cancer patients treated with immunotherapy, especially when chemotherapy is not needed.

## Contribution

ALI is shown to be a stronger predictor of treatment success than existing biomarkers in immunotherapy for advanced lung cancer.

## Key findings

- High ALI scores are linked to longer survival in immunotherapy-treated lung cancer patients.
- ALI is a better predictor than PD-L1, NLR, and other scores for immunotherapy outcomes.
- For PD-L1-high patients, ALI >18 suggests immunotherapy alone may be sufficient.

## Abstract

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).

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.

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.

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.

•ALI is prognostic and predictive for patients with advanced NSCLC treated with immunotherapy monotherapy, but not chemo-immunotherapy.•Its association with outcomes is stronger than that of other parameters (PD-L1 TPS, NLR, lung immune prognostic index, EPSILoN).•For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

ALI is prognostic and predictive for patients with advanced NSCLC treated with immunotherapy monotherapy, but not chemo-immunotherapy.

Its association with outcomes is stronger than that of other parameters (PD-L1 TPS, NLR, lung immune prognostic index, EPSILoN).

For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.