Elevated CRP levels indicate poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors

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http://hdl.handle.net/10138/306819

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Iivanainen , S , Ahvonen , J , Knuuttila , A , Tiainen , S & Koivunen , J P 2019 , ' Elevated CRP levels indicate poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors ' , ESMO open , vol. 4 , no. 4 , 000531 . https://doi.org/10.1136/esmoopen-2019-000531

Title: Elevated CRP levels indicate poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors
Author: Iivanainen, Sanna; Ahvonen, Jarkko; Knuuttila, Aija; Tiainen, Satu; Koivunen, Jussi Pekka
Contributor: University of Helsinki, HUS Comprehensive Cancer Center
Date: 2019-07
Number of pages: 7
Belongs to series: ESMO open
ISSN: 2059-7029
URI: http://hdl.handle.net/10138/306819
Abstract: Background Anti-PD-(L)1 agents are standard of care treatments in various cancers but predictive factors for therapy selection are limited. We hypothesised that markers of systemic inflammation would predict adverse outcomes in multiple cancers treated with anti-PD-(L)1 agents. Material and methods Discovery cohort consisted of patients who were treated with anti-programmed cell death protein-1 (PD-1) agents for advanced melanoma (MEL), non-small cell lung cancer (NSCLC) or renal and bladder cancers (GU) at Oulu University Hospital and had pretreatment C reactive protein (CRP), or neutrophil/lymphocyte values available. As a validation cohort, we collected patients treated with anti-PD-1 agents from three other hospitals in Finland. Results In the discovery cohort (n=56, MEL n=23, GU n=17, NSCLC n=16), elevated CRP over the upper limit of normal (ULN) (>10mg/mL) indicated poor progression-free (PFS; p=0.005) and overall survival (OS; p=0.000004) in the whole population and in MEL subgroup. Elevated neutrophil-to-lymphocyte ratio (>2.65) also indicated inferior PFS (p=0.02) and OS (p=0.009). In the validation cohort (n=107,MEL n=44, NSCLC n=42, GU n=17, other n=4), CRP over ULN also was a strong indicator for poor PFS (p=0.0000008), and OS (p=0.000006) in the whole population, and in MEL and NSCLC also. Conclusions Systemic inflammation suggested by elevated CRP is a very strong indicator for adverse prognosis on patients treated with anti-PD-(L)1 agents and has a potential negative predictive value for treatment with anti-PD-(L)1 agents. Prospective trials should investigate whether patients with elevated CRP gain any significant benefit from anti-PD-1 therapy.
Subject: PD-1
CRP
prognostic
predictive
survival
MUTATIONAL LANDSCAPE
CLINICAL-RESPONSE
NIVOLUMAB
PEMBROLIZUMAB
INFLAMMATION
IPILIMUMAB
DOCETAXEL
MELANOMA
ANTIBODY
THERAPY
3122 Cancers
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