University of Oulu

Iivanainen S, Ahvonen J, Knuuttila A, et al. Elevated CRP levels indicate poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors. ESMO Open 2019;4:e000531. doi: 10.1136/esmoopen-2019-000531

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

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Author: Iivanainen, Sanna1; Ahvonen, Jarkko2; Knuuttila, Aija3;
Organizations: 1Department of Oncology and Radiotherapy, MRC Medical Reasearch Center, Oulu University Hospital, Oulu, Finland
2Department of Oncology, Tampere University Hospital, Tampere, Finland
3Department of Pulmonary Medicine, Heart and Lung Center and Cancer Center, Helsinki University Hospital, Helsinki, Finland
4Cancer Center, Kuopio University Hospital, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020042119538
Language: English
Published: BMJ, 2019
Publish Date: 2020-04-21
Description:

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) (>10 mg/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.

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Series: ESMO open
ISSN: 2059-7029
ISSN-E: 2059-7029
ISSN-L: 2059-7029
Volume: 4
Issue: 4
Article number: e000531
DOI: 10.1136/esmoopen-2019-000531
OADOI: https://oadoi.org/10.1136/esmoopen-2019-000531
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
CRP
Funding: This work was supported by Oulu University and Finnish Cancer Institute.
Copyright information: © Author (s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, any changes made are indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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