Early NLR Changes Predict mRCC Immunotherapy Outcomes

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Rises and decreases in neutrophil-to-lymphocyte ratio at 6 weeks after treatment with anti-PD-1/PD-L1 immune checkpoint blockade is associated with progression-free and overall survival.
Rises and decreases in neutrophil-to-lymphocyte ratio at 6 weeks after treatment with anti-PD-1/PD-L1 immune checkpoint blockade is associated with progression-free and overall survival.

Changes in neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma (mRCC) independently predicts outcomes, investigators reported at the European Society for Medical Oncology 2017 Congress in Madrid.

In a study of 142 patients with mRCC who received anti-PD-1/PD-L1 immune checkpoint blockade (ICB), Aly-Khan A. Lalani, MD, and colleagues at the Dana-Farber Cancer Institute in Boston found that higher 6-week NLR was independently associated with reduced objective response rate (ORR, partial or complete response) and shorter progression-free survival (PFS) and overall survival (OS).

The study, which was presented by Dr Lalani, showed that compared with patients who had no change in NLR from baseline to 6 weeks, those who experienced a 25% or greater relative decrease in NLR during that period had a 52% increased likelihood of responding to treatment, a 45% decreased risk of radiographic or clinical progression, and 67% decreased risk of death, in adjusted analyses. Patients who experienced a 25% or greater increase in NLR from baseline to 6 weeks had a 55% decreased likelihood of responding to treatment, 2.6 times increased risk of radiographic or clinical progression, and 1.57 times increased risk of death.

“The results of analyses at 6-weeks on ICB therapy are informative for both patients and physicians given that this time point typically coincides with the first set of re-staging scans after initiation of treatment,” Dr Lalani, a Genitourinary Oncology Fellow at Dana-Farber's Lank Center for Genitourinary Oncology, told Renal & Urology News. “For example, if a patient presents at 6-weeks on ICB therapy with stable or slightly progressive disease on imaging and a simultaneous decline in NLR, this may be reassuring to continue treatment assuming it is otherwise clinically suitable. Taken together, our data suggest that NLR appears to be a readily available, prognostic marker in mRCC patients treated with conventional ICB, and warrants larger, prospective validation.”

The study, whose senior author was Toni K. Choueiri, MD, Director of the Lank Center for Genitourinary Oncology, demonstrated that NLR at 6 weeks was a significantly stronger predictor of ORR, PFS, and OS than baseline NLR.

Previous studies have demonstrated that an elevated NLR is associated with a poor prognosis among patients with various types of solid tumors. The prognostic value of NLR in the current era of ICB has been evaluated in small subsets of patients, such as those with lung, melanoma, and bladder malignancies, but its utility in the context of contemporary immunotherapy for mRCC has not been well defined, Dr Lalani said.

Of the 142 patients, 53.5% received monotherapy and 46.5% received combination therapy. Based on IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) criteria, 18.3%, 59.9%, and 21.8% of patients had favorable, intermediate, and poor risk disease at the start of treatment.

Reference

Lalani AK, Xie W, Martini DJ, et al. Change in neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. Data presented at the European Society for Medical Oncology 2017 Congress in Madrid, Spain, September 8-12. Poster 888P.

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