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. 2018 Jan 22;6(1):5.
doi: 10.1186/s40425-018-0315-0.

Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma

Aly-Khan A Lalani  1 , Wanling Xie  2 , Dylan J Martini  1   3 , John A Steinharter  1 , Craig K Norton  1 , Katherine M Krajewski  4 , Audrey Duquette  1 , Dominick Bossé  1 , Joaquim Bellmunt  1 , Eliezer M Van Allen  1   5 , Bradley A McGregor  1 , Chad J Creighton  6 , Lauren C Harshman  1 , Toni K Choueiri  7
Affiliations

Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma

Aly-Khan A Lalani et al. J Immunother Cancer. .

Abstract

Background: An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB.

Methods: We examined NLR at baseline and 6 (±2) weeks later in 142 patients treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA). Landmark analysis at 6 weeks was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Cox and logistic regression models allowed for adjustment of line of therapy, number of IMDC risk factors, histology and baseline NLR.

Results: Median follow up was 16.6 months (range: 0.7-67.8). Median duration on therapy was 5.1 months (<1-61.4). IMDC risk groups were: 18% favorable, 60% intermediate, 23% poor-risk. Forty-four percent were on first-line ICB and 56% on 2nd line or more. Median NLR was 3.9 (1.3-42.4) at baseline and 4.1 (1.1-96.4) at week 6. Patients with a higher baseline NLR showed a trend toward lower ORR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was a significantly stronger predictor of all three outcomes than baseline NLR. Relative NLR change by ≥25% from baseline to 6 weeks after ICB therapy was associated with reduced ORR and an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.004), whereas a decrease in NLR by ≥25% was associated with improved outcomes.

Conclusions: Early decline and NLR at 6 weeks are associated with significantly improved outcomes in mRCC patients treated with ICB. The prognostic value of the readily-available NLR warrants larger, prospective validation.

Keywords: Immunotherapy; Neutrophil-to-lymphocyte ratio; PD-1/pd-L1 PD-L1; Prognostic biomarker; Renal cell carcinoma.

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Conflict of interest statement

Authors information

Not applicable.

Ethics approval and consent to participate

The study was approved by the local institutional review boards and was conducted in accordance with Good Clinical Practice Guidelines and the Declaration of Helskinki.

Consent for publication

Informed consent for publication has been obtained and the consent forms are held by the authors.

Competing interests

AAL: honoraria/consulting from Novartis; conference travel expenses from Pfizer.

WX: honoraria/consulting from Bayer.

JB: honoraria/consulting from Astellas, Genentech, Merck, Novartis, Pfizer, Pierre Fabre; institutional research funding/support from Millenium, Sanofi, MSD Oncology, Pfizer.

EMVA: honoraria/consulting from Genome Medical, Novartis, Roche, Syapse, Takeda, Third Rock Ventures; institutional research funding/support from Bristol-Myers Squibb, Novartis.

BAM: honoraria/consulting from Astellas, Seattle Genetics, Bayer, Astra-Zeneca, Genentech and Exelixis.

LCH: honoraria/consulting from Genentech, Pfizer, Dendreon, NCCN, Medivation/Astellas, KEW, Corvus, Merck; institutional research funding/support from Bayer, Medivation/Astellas, Pfizer, Dendreon, Sotio, Genentech, Merck, BMS, Jannsen.

TKC: honoraria/consulting from Alligent, AstraZeneca, Bayer, Bristol-Myers Squibb, Cerulean Pharma, Eisai, Exelixis, Foundation Medicine, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, Prometheus, Roche/Genentech; institutional research funding/support from Pfizer, Exelixis, Bristol-Myers Squibb, Novartis, Peloton, AstraZeneca, Agensys, TRACON.

The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Neutrophil-to-lymphocyte ratio (NLR) at start of anti-PD-1/PD-L1 therapy by a IMDC risk groups and b Histology (clear cell RCC, ccRCC; non-clear cell RCC, nccRCC)
Fig. 2
Fig. 2
Estimated a 6-month and 1-year PFS rate, and b 1- and 2-year OS rate from Cox regression based on continuous neutrophil-to-lymphocyte ratio (NLR) at week 6 (±2 weeks). NLR was modeled on the natural logarithmic scale and transformed back to the original scale for graphic presentation. PFS and OS were calculated from 6 weeks of therapy
Fig. 3
Fig. 3
Neutrophil-to-lymphocyte ratio (NLR) at week 6 (a) and percent (%) change of NLR at week 6 (b) according to response to therapy (complete/partial response, CR/PR; stable disease, SD; progressive disease, PD)
Fig. 4
Fig. 4
PFS and OS according to change of neutrophil-to-lymphocyte ratio (NLR) at 6 weeks, separately by baseline NLR status (Low vs High, dichotomized at the median)
Fig. 5
Fig. 5
Computed tomography (CT) scans at baseline, 6-week, and subsequent assessment for two separate mRCC patients treated with PD-1/PD-L1 ICB. The first patient (upper panels) had stable disease (SD) on 6-week scan with a 34% decrease in NLR from baseline and subsequently displayed partial response (PR) on next assessment. The second patient (lower panels) had SD on 6-week scan with a 113% increase in NLR from baseline and subsequently displayed progressive disease (PD) on next assessment. Arrows (white) show change in selected area of disease burden
See this image and copyright information in PMC

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