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The Lung Immune Prognostic Index May Indicate Response to Immune Checkpoint Inhibitors in Patients with MSI-H or dMMR Tumours

Immune checkpoint inhibitor treatment is used for tumours with microsatellite instability high or mismatch repair deficiency but not all of these patients respond
09 Dec 2020
Cancer Immunology and Immunotherapy

The lung immune prognostic index (LIPI) may be useful in identifying patients having tumours with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) who are likely to have no or poor response following treatment with an immune checkpoint inhibitor (ICI), including those at risk of fast progression. These  findings were presented at the ESMO Immuno-Oncology Virtual Congress 2020, held from 9 to 12 December 2020.

In a poster presentation, lead author Edouard Auclin of the Hôpital Européen Georges-Pompidou in Paris, France explained that MSI-H/dMMR is considered the first predictive marker for the efficacy of ICIs with tissue/site-agnostic approval. Nevertheless, according to the authors, approximately 39% of cases are refractory to ICI treatment and, to date, no additional biomarkers have been determined to identify these at-risk patients.

The investigators conducted this multicentre retrospective study to evaluate the prognostic value of the LIPI performed prior to ICI treatment in patients with MSI-H/dMMR to identify patients who may be poor responders or at risk of fast progression.

The study enrolled patients with metastatic MSI-H/dMMR tumours receiving ICIs from April 2014 to May 2019. The LIPI was calculated based on the derived neutrophil to lymphocyte ratio (dNLR) consisting of neutrophils and/or leucocytes-neutrophils >3 plus lactate dehydrogenase (LDH) greater than the upper limit of normality (ULN), as reported in the literature. The patients were categorised into one of three LIPI groups: good (0 factors), intermediate (1 factor), and poor (2 factors).

Overall survival (OS), including patients with fast progression, defined as overall survival (OS) < 3 months served as the primary endpoint while the secondary endpoint was progression-free survival (PFS).

Patients in the LIPI poor category had the poorest survival

The study identified 151 patients treated with ICIs; 59% of patients were female with a median age of 64 years. Sixty-eight percent of patients had ECOG performance status (PS) >1; 68% also had sporadic dMMR status. An ICI was administered as first or second line treatment in 59% of patients. The most frequent tumour types were gastrointestinal in 66% and gynaecological in 22% of patients.

The LIPI group classification was good in 67 (47%) patients, intermediate in 62 (43%), and poor in 14 (10%) patients.

With median follow-up of 32 months, the 24-month OS rates according to the good, intermediate, and poor risk LIPI groups were 71.1%, 54.2%, and 14.3%, respectively (p < 0.0001).

Upon analysis that adjusted for tumour site, metastatic sites, and PS, the LIPI classification of poor remained independently associated with OS (hazard ratio [HR] 3.2; 95% confidence interval [CI] 1.3-7.9, p = 0.03).

Among patients in the poor LIPI group, 16% to 35.7% of patients were fast progressors compared to 7.5% of patients with good LIPI status (p = 0.02).

The odds ratio (OR) for a fast progression event in the poor group was 6.9 [95% CI 1.7-28.6; p = 0.01].

In the patients overall, median PFS was 10.5 months (95% CI 7.1-35.1). Median PFS according to good, intermediate, and poor LIPI groups was 20.9 months (95% CI 8.4-not reached [NR]), 9.9 months (95% CI 2.8-NR), and just 2.3 months (95% CI 1.8-NR), respectively (p < 0.0001).

The-Lung-Immune-Prognostic-Index-May-Indicate-Response-to-Immune-Checkpoint-Inhibitors-in-Patients-with-MSI-H-or-dMMR-Tumours

Kaplan Meier curve for overall survival (Panel A) and progression-free survival (Panel B) according to LIPI score. Log Rank p < 0.0001 for both endpoints.

© Edouard Auclin.

Conclusions

According to the authors, the LIPI can identify patients with MSI-H and /or dMMR tumours that do not benefit from ICI treatment, particularly the fast progressors.

They recommend that the LIPI be included as stratification factor in future trials.

No external funding was reported for this study.

Reference

2P – Auclin E, Vuagnat P, Smolenschi C, et al. Lung immune prognostic index (LIPI) can identify the fast-progressor to immune checkpoints inhibitors (ICI) in microsatellite instability (MSI) or mismatch repair deficient (dMMR) tumours. ESMO Immuno-Oncology Virtual Congress 2020 (9-12 December).

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