Neutrophil-lymphocyte ratio predicts response to immunotherapy in NSCLC

BY CHRISTINE KILGORE
MDedge News

SAN FRANCISCO – For patients with non–small cell lung cancer, the ratio of neutrophils to lymphocytes appears to be predictive of response to immune checkpoint inhibitors, a finding that could aid in treatment planning, investigators suggest.

Among 123 patients with non–small cell lung cancer (NSCLC) who received monotherapy with an immune checkpoint inhibitor, those with a low neutrophil-to-lymphocyte ratio (NLR) had markedly longer overall survival than did patients with high NLR, regardless of mutational status, reported Arpeet T. Shah, MD, and his colleagues from Stanford (Calif.) University and the Stanford Cancer Institute.

“Those patients with EGR, ALK alterations don’t do as well with immunotherapy. The question is can we figure out which patients do well?” Dr. Shah said in an interview at the ASCO (American Society of Clinical Oncology)– SITC (Society for Immunotherapy of Cancer): Clinical Immuno-Oncology Symposium.

Immune checkpoint inhibitors are used in the first-line setting for patients in NSCLC without alterations in either EGFR or ALK, and in the second line for patients with driver mutations in EGFR and/or ALK.

But as Dr. Shah (shown left) and his colleagues noted in a poster presentation, there is evidence to suggest that immune checkpoint inhibitors targeted against programmed death protein 1 (PD-1) and its ligand (PD-L1) are less effective in patients with these mutations (Clin Cancer Res. 2016 Sep 15;22[18]:4585-93).

They also noted that NLR has been found to be a predictive biomarker in two systematic reviews and meta-analyses (Thorac Cancer. 2018 Oct; 9[10]:1220-30 and Onco Targets Ther. 2018 Feb 23;11:955-65).

To evaluate clinical and molecular characteristics of patients with NSCLC who respond to single-agent checkpoint inhibitor therapy and assess the predictive role of NLR, the Stanford investigators took a retrospective look at 123 patients with NSCLC at their center who received immunotherapy with a checkpoint inhibitor during April 2015–June 2018.

They defined a low NLR at the start of therapy as less than 5.9, and a high ratio as 5.9 or greater. They used time on therapy (180 days or more than or less than 180 days) to identify responders vs. nonresponders.

They found that, among 23 responders for whom genomic testing results were available, 6 (22%) had alterations in EGFR, ALK, and/or ROS1, compared with 27 of 74 (36%) nonresponders.

In addition, they saw that 89% of responders had an associated radiographic response, compared with just 9% of nonresponders (P less than .001).

Median overall survival for patients with driver mutations was 4.2 months from the start of checkpoint inhibitor therapy, compared with 8.1 months for patients without mutations, but this trend was not statistically significant, probably because of the relatively small sample sizes.

When they looked at NLR as a predictive marker, however, they saw that, for patients both with and without driver mutations, high NLR was associated with worse outcomes.

The median overall survival for patients with alterations in EGFR, ALK or ROS1 with high NLR was 2 months, compared with 8.1 months for similar patients with low NLR.

For patients without mutations, median overall survival for those with high NLR was 4.3 months, compared with 12.1 months for those with low NLR (P = .033).

Dr. Shah said that the next step is to delineate why the six patients with driver mutations who had responses to checkpoint inhibitors did better than the majority of patients with mutations.

“We need to figure out which of these patients is going to do well, and that can definitely inform practice,” he said.

The study was internally supported. Dr. Shah reported having no conflicts of interest.