Study: Host Immune Classifier Test Predicts ICI Response in Advanced NSCLC

Patients treated with immune checkpoint inhibitors had significantly different survival rates based on the test, regardless of PD ligand 1 classification.

A blood-based proteomic test can help identify patients with non-small cell lung cancer (NSCLC) who are unlikely to benefit from immune checkpoint inhibitor (ICI) therapy, according to a new study.

The report builds on earlier research suggesting that the test, known as a host immune classifier (HIC), can be a helpful tool in choosing treatment regimens. The study was published in the Journal for ImmunoTherapy of Cancer.

ICIs have been an important treatment option for patients with NSCLC, but the therapy does not work for all patients. Current recommendations state that ICI monotherapy is a good fit for patients with tumor PD ligand 1 (PD-L1) expression greater than 50%, while ICI combined with chemotherapy is indicated for patients with all PD-L1 expression levels.

Yet, corresponding author Wallace Akerley, MD, of the University of Utah, and colleagues, wrote that those guidelines are far from predictive of outcomes. Only about 30% of patients with PD-L1 ≥50% achieve 5-year survival, and some patients have succeeded with first-line ICI monotherapy despite not meeting eligibility criteria under current guidelines.

“Considering the inconsistent correlation between PD-L1 expression and ICI efficacy, the significant adverse events profile of ICI, and their cost to the patient and the health care system, finding additional indicators of patient benefit from ICI combinations or monotherapy is a focus for both physicians and patients,” Akerley and colleagues wrote.

The HIC test is a measure of systemic inflammatory state, classifying patients into 2 groups: HIC-Hot and HIC-Cold. Previous research has shown the test to be a useful predictive tool in patients receiving targeted therapy and chemotherapy-based regimens, but only one previous study has looked at HIC as a biomarker for ICI therapy.

In order to bolster the evidence regarding HIC’s utility, Akerley and colleagues used the observational INSIGHT study, which included 35 treatment sites in the United States, and included HIC testing for all patients. The study enrolled more than 3500 patients, but Akerley and colleagues focused on patients with advanced stage (IIIB and IV) NSCLC. Of those, 877 patients received first-line therapies while in the study, and 284 of those patients received regimens including ICIs.

The data showed patients in the HIC-Hot classification had significantly longer overall survival than patients categorized as HIC-Cold, regardless of treatment. However, the differences were stark among patients treated with ICIs. Among patients treated with any ICI regimen, median overall survival (OS) was just 5 months among HIC-Cold patients, but median OS was not met in the HIC-Hot group. In patients receiving ICI monotherapy, HIC-Cold patients had an OS of 2.8 months, compared with 16.8 months in the HIC-Hot group. For those given ICI with chemotherapy, HIC-Cold patients had an OS of 6.4 months, and the median OS was unreached in the HIC-Hot Group.

Akerley and colleagues said these data suggest patients who are HIC-Cold are not good candidates for ICI monotherapy, even if their PD-L1 expression levels indicate the therapy.

“While PD-L1 is viewed as the standard biomarker for PD-1-based immunotherapy for lung cancer, these data add to the body of evidence that checkpoint pathways represent a network that involves many other elements besides the PD-1/PD-L1 complex,” they wrote.

They concluded that physicians should consider using HIC testing alongside PD-L1 testing when deciding which treatment path to take.


Rich P, Mitchell RB, Schaefer E, et al. Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer. J Immunother Cancer. Published online October 27, 2021. doi:10.1136/jitc-2021-002989

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