16 juli 2020: Bron: Cancer Immunology june 19th. 2020

Wanneer kankerpatiënten behandeld worden met immuuntherapie met een anti-PD medicijn blijkt het meten tijdens de behandeling van de veranderingen in de verhouding van de neutrofielen tot de lymfocyten ratio (NLR) in het bloed een eenvoudige manier om de effectiviteit te meten. 
De NLR = Neutrofiel/lymfocyt-ratio en PLR = trombocyt/lymfocyt-ratio zijn als basismeting sowieso bij vele vormen van kanker voorspellende factoren voor de overall overleving.
Maar uit een recente studie blijkt het meten van de verhouding van de neutrofielen tot de lymfocyten ratio (NLR) op enkele momenten tijdens de behandeling sterke aanwijzingen te geven voor het verloop van de ziekte. 

Uit deze bron: "De NLR wordt berekend door het aantal neutrofielen door het aantal lymfocyten te delen en wordt voor meerdere vormen van kanker als een mogelijke overlevingsmarker beschouwd. Trombocyten spelen een rol bij de metastase van kanker en de PLR wordt ook steeds vaker als een prognostische biomarker onderzocht."

In een retrospectieve studie uitgevoerd met gegevens van drie Franse ziekenhuizen, werden patiënten die werden behandeld met nivolumab voor niet-kleincellige longkanker (NSCLC) of uitgezaaide nierkanker (mRCC) geëvalueerd op basis van de verhouding tussen neutrofielen en lymfocyten ratio (NLR) en het verband tussen NLR scores met de effectiviteit van de behandeling.

Aan het onderzoek namen 161 patiënten deel, 75 longkankerpatiënten en 86 nierkankerpatiënten met uitgezaaide tumoren deel (28% gunstig risico; 53% gemiddeld risico; en 11% slecht risico), met een mediane progressievrije ziekte (PFS) en overall oveleving (OS) van respectievelijk 4,6 maanden en 24,7 maanden. NLR-variaties werden onderzocht vanaf de start van de studie - vóór eerste toediening - tot en met elke keer dat nivolumab weer werd gegeven tot de datum van de eerste CT - scan. (tussen week 8 en 12).

Voor de groep van nierkankerpatiënten waren de mediane progressievrije ziekte (PFS) en mediane overall overleving (OS) 13,6 maanden versus 3,6 maanden (P = .003) en PFS niet bereikt versus OS van 19,6 maanden (P = .008) voor patiënten met respectievelijk een NLR-afname versus een NLR-toename.

In een multivariabele analyse bleef elke NLR-toename in week 6 onafhankelijk geassocieerd met een slechtere progressievrije ziektetijd - PFS (HR, 2,2; P = .01) en overall overleving - OS (HR, 1,7; P = .09).

NLR score was bij de start significant hoger bij patiënten met progressieve ziekte in vergelijking met patiënten met stabiele ziekte of gedeeltelijke en volledige respons (P = .048).

Conclusie van de onderzoekers: 

Elke toename van het NLR in week 6 ging gepaard met slechtere PFS- en OS-resultaten. NLR-variatie is een goedkope en dynamische marker die gemakkelijk kan worden verkregen om de werkzaamheid van anti-PD-1 te controleren. Dus het meten van de neutrofielen tot de lymfocyten ratio (NLR) tijdens de behandeling is een goedkope en eenvoudige manier om de werkzaamheid van immuuntherapie met anti-PD medicijnen vroegtijdig te herkennen. 

Het studierapport Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab is tegen betaling in te zien.

Hier het abstract van de studie plus referentielijst:

Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab

Abstract

Background

An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment.

Patients and methods

All pts with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC) who received anti-PD1 nivolumab monotherapy in second-line setting or later were included in this French multicentric retrospective study. NLR values were prospectively collected prior to each nivolumab administration. Clinical characteristics were recorded. Associations between baseline NLR, NLR variations and survival outcomes were determined using Kaplan–Meier’s method and multivariable Cox regression models.

Results

161 pts (86 mRCC and 75 mNSCLC) were included with a median follow-up of 18 months. On the whole cohort, any NLR increase at week 6 was significantly associated with worse outcomes compared to NLR decrease, with a median PFS of 11 months vs 3.7 months (< 0.0001), and a median OS of 28.5 months vs. 18 months (p = 0.013), respectively. In multivariate analysis, NLR increase was significantly associated with worse PFS (HR 2.2; p = 6.10−5) and OS (HR 2.1; p = 0.005). Consistent results were observed in each cohort when analyzed separately.

Conclusion

Any NLR increase at week 6 was associated with worse PFS and OS outcomes. NLR variation is an inexpensive and dynamic marker easily obtained to monitor anti-PD1 efficacy.

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Data availability

Not applicable.

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Funding

The investigators AS, YA had access to the raw data. All authors approved the final manuscript. The corresponding author had full access to all the data, and takes final responsibility for the manuscript submitted for publication.

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Contributions

AS, RE, SO and YAV were involved in the study design and concept. AS, YAV, EF, VF, DB, JT, PB, CT were involved in the identification and selection of patients. AS and RE were involved in the statistical analysis. LF was involved in the radiographic evaluation. All authors were involved in the review and editing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Y. A. Vano.

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Conflict of interest

YV, SO, CT and PB: consulting fees from BMS, MSD, Pfizer, Novartis, Ipsen, Roche, Astellas, Sanofi, Janssen. DB: funding to institution for clinical research, advisory role or travel accommodation: Bristol-Meyers Squibb, Pfizer, Roche, Ipsen, MSD, Astra-Zeneca. No potential conflicts of interest were disclosed by the other authors.

Ethics approval and consent to participate

The study was approved by the local institutional review board and was conducted with Good Clinical Practice Guidelines and the Declaration of Helsinki. All patients gave their oral consent. CNIL declaration No 2215794 v 0

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Simonaggio, A., Elaidi, R., Fournier, L. et al. Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab. Cancer Immunol Immunother (2020). https://doi.org/10.1007/s00262-020-02637-1


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