Universität zu Köln

Brueckl, Natalie F., Wirtz, Ralph M., Reich, Fabian P. M., Veltrup, Elke, Zeitler, Gloria, Meyer, Christian, Wuerflein, Dieter, Ficker, Joachim H., Eidt, Sebastian and Brueckl, Wolfgang M. (2021). Predictive value of mRNA expression and dynamic changes from immune related biomarkers in liquid biopsies before and after start of pembrolizumab in stage IV non-small cell lung cancer (NSCLC). Transl. Lung Cancer Res., 10 (11). S. 4106 - 4123. SHATIN: AME PUBL CO. ISSN 2226-4477

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Abstract

Background: The aim of this study was to determine whether mRNA expressions and dynamic changes of immune-related genes before and after starting first-line treatment with the PD-1 inhibitor pembrolizumab in patients with NSCLC were of predictive value. Methods: CD3, CD8, PD-1, PD-L1 and CTLA-4 mRNA expression levels were measured from peripheral blood before and after three weeks of treatment with the PD-1 inhibitor. Univariate and multivariate analyses were performed retrospectively. Response, progression-free survival (PFS) and overall survival (OS) were determined. Results: In univariate analysis an increase of CD3 and CD8 mRNA expression after the first cycle of pembrolizumab were each associated with improved PFS and OS. In contrast, patients with no change or with a decrease in CD3 and CD8 mRNA expression showed significantly worse outcome. CD8 mRNA increase remained an independent predictive factor for PFS and OS in the multivariate analysis with p values of 0.011 and 0.006, respectively. Conclusions: An increase of CD8 mRNA expression predicts favorable outcome after first line monotherapy with pembrolizumab, while no change or decrease might serve as an indicator of poor outcome and might give cause for early treatment escalation for instance by addition of chemotherapy or additional ICI treatment, e.g., against CTLA-4.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brueckl, Natalie F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reich, Fabian P. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Veltrup, Elke UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeitler, Gloria UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wuerflein, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Ficker, Joachim H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eidt, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Brueckl, Wolfgang M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-584988
DOI:	10.21037/tlcr-21-587
Journal or Publication Title:	Transl. Lung Cancer Res.
Volume:	10
Number:	11
Page Range:	S. 4106 - 4123
Date:	2021
Publisher:	AME PUBL CO
Place of Publication:	SHATIN
ISSN:	2226-4477
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TO-LYMPHOCYTE RATIO; OPEN-LABEL; PERIPHERAL-BLOOD; PD-1 BLOCKADE; DOCETAXEL; NIVOLUMAB; ATEZOLIZUMAB; CHEMOTHERAPY; MULTICENTER; PHASE-3 Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58498