Language

English

Publication Date

4-1-2025

Journal

The Journal of Thoracic and Cardiovascular Surgery

DOI

10.1016/j.jtcvs.2024.10.005

PMID

39395787

PMCID

PMC11949723

PubMedCentral® Posted Date

4-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Background: Immune checkpoint therapy (ICT) has significantly impacted the treatment of malignant pleural mesothelioma (MPM). Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT.

Methods: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of mesothelin and PD-L1. Both univariable and multivariable Cox regression analyses were used to determine independent prognosticators for overall survival (OS). A prospective ICT clinical trial and our historical cohort were included for validation.

Results: Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, and the remaining 38% received combination ICT. Higher pre-ICT SMRP levels were observed in epithelioid MPM compared to nonepithelioid MPM. Serum PD-L1 levels did not differ significantly between the different histologic groups. Univariable analysis identified durable clinical benefit, development of immune-related adverse events, and SMRP levels as significantly associated with OS. Multivariable analysis confirmed SMRP as an independent prognostic factor, with lower levels (≤1.35 nmol/L) correlating with improved OS. The association of high SMRP with worse prognosis was validated in the prospective ICT clinical trial cohort and not in our historical cohort treated without ICT.

Conclusions: SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.

Keywords

Humans, Male, Female, Mesothelin, Pleural Neoplasms, Middle Aged, Aged, Retrospective Studies, Mesothelioma, Malignant, GPI-Linked Proteins, Biomarkers, Tumor, Immune Checkpoint Inhibitors, B7-H1 Antigen, Treatment Outcome, Immunotherapy, Lung Neoplasms, Mesothelioma, Predictive Value of Tests, mesothelioma, liquid biomarker, SMRP, soluble PD-L1, prognostic biomarker, checkpoint immunotherapy

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.