Association of Lung Immune Prognostic Index (LIPI) with Disease Control Rate and Progression-Free Survival in Patients with Soft-Tissue Sarcoma Treated with Immunotherapy in Early-Phase Trials.

Background: The efficacy of immunotherapies in soft-tissue sarcomas (STSs) is limited, and biomarkers of response are lacking. The lung immune prognostic index (LIPI) is a prognostic biomarker used with immunotherapy across cancer types. This study investigates the association of LIPI with the disease control rate (DCR) and progression-free survival (PFS) in patients with STS treated with immunotherapy versus other therapies in early-phase trials.

Methods: This post hoc analysis was conducted with patients with STS from Gustave Roussy and Centre Léon Bérard between January 2012 and June 2021. The LIPI was calculated based on a derived neutrophil-to-lymphocyte ratio > 3 and elevated lactate dehydrogenase. Patients were categorized based on treatment (immunotherapy or other) and LIPI (good, intermediate, or poor). DCR was defined as the sum of stable disease and complete and partial response.

Results: A total of 82 patients were enrolled in immunotherapy trials and 126 in the other therapy trials. In the immunotherapy group, DCR was higher in patients with good LIPI (76%; = 23/30) compared with the intermediate (50%; = 13/26) and poor LIPI groups (8%; = 1/12; < 0.001). The other-therapy group did not show significant differences in DCR by LIPI: DCR was 70% ( = 48/69), 70% ( = 21/30), and 60% ( = 6/10) in patients with good, intermediate, and poor LIPI, respectively ( = 0.86). In multivariate analyses, LIPI was independently associated with PFS in the immunotherapy group (hazard ratio = 5.97, = 0.0001) and not in the control group ( = 0.71).

Conclusions: LIPI is a significant independent prognostic marker for DCR in patients with STS treated with immunotherapy. In early-phase trials, LIPI could be used as a screening tool for stratification at inclusion. High neutrophil levels, which correlate with a poorer LIPI score, are likely associated with immunotherapy resistance. This relationship could explain the statistical impact of poor LIPI in the immunotherapy group.