Poor Baseline LIPI Associated With Worse Outcomes for ICI Treatment in Patients With NSCLC

Combining derived neutrophils ratio (dNLR) greater than 3 and lactate dehydrogenase (LDH) levels greater than the upper limit of normal (ULN) was correlated with worse outcomes for immune checkpoint inhibitor (ICI) treatment in patients with non—small-cell lung cancer (NSCLC), but not with chemotherapy, according to a study in JAMA Oncology.

While immunotherapy has gained worldwide approval as treatment for advanced NSCLC, response rates with single ICIs range from 14% to 20%, according to the authors of the study. When the cohort is stratified by specific biomarkers, particularly positive PD-L1 expression, the response rate reaches up to 30%. However, the benefit is not seen for the entire group, making the identification of biomarkers for patients likely to respond to ICI a critical step in selecting patients.

The inflammation process has been offered as a mechanism of immunoresistance in patients with cancer. According to the authors, numerous routine blood parameters have been investigated as potential inflammatory biomarkers in patients with cancer, such as LDH level, which is associated with poor outcomes in several cancer types. The authors continued: “Novel potential biomarkers such as the neutrophil to lymphocyte ratio (NLR) and dNLR have been investigated to measure inflammatory status in various cancer, including NSCLC.”

The authors conducted a multicentric retrospective study of 466 patients with advanced NSCLC receiving treatment with PD-1/PD-L1 inhibitors. Patients from Gustave Roussy treated with PD-1/PD-L1 inhibitors between November 2012 and July 2016 were included in the test set (n = 161). Patients from 8 European academic centers treated with PD-1/PD-L1 inhibitors between November 2012 and January 2017 were included in the validation set (n = 305). A control cohort of 162 patients treated with chemotherapy was also included.

Complete blood cell counts, LDH, and albumin levels were measured before ICI treatment. A Lung Immune Prognostic Index (LIPI) was developed on the basis of dNLR greater than 3 and LDH greater than ULN, determining 3 groups: good, 0 factors; intermediate, 1 factor; poor, 2 factors.

Among the 129 patients with PD-L1 data, 74% (96) had PD-L1 of at least 1% by immunohistochemical analysis, and 26% (33) had negative results. In the test set, median progression-free survival (PFS) was 3 months, and overall survival (OS) was 10 months. A dNLR greater than 3 and LDH greater than ULN were independently associated with OS (HR, 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95% CI, 1.32-4.76, respectively).

Median PFS was 2 months for poor LIPI, 3.7 months for intermediate LIPI, and 6.3 months for good LIPI. Median OS for poor, intermediate, and good LIPI was 3 months, 10 months, and 34 months, respectively. Disease control rate (DCR) was also associated with dNLR greater than 3 and LDH greater than ULN. Results were reproducible in the ICI validation cohort for OS, PFS, and DCR, but were nonsignificant in the chemotherapy cohort.

“Poor baseline LIPI, combining dNLR greater than 3 and LDH greater than ULN, was correlated with poor outcomes with immunotherapy, but not chemotherapy, raising the hypothesis that LIPI might not be useful for identifying patients unlikely to benefit from treatment,” concluded the authors.