• Sonali Mitra, Hee-Jin Jang, Allen Kuncheria, Sung Wook Kang, Jong Min Choi, Ji Seon Shim, Claire Lee, Priyanka Ranchod, Peter Jindra, Maheshwari Ramineni, Meera Patel, R Taylor Ripley, Shawn S Groth, Shanda H Blackmon, Bryan M Burt, and Hyun-Sung Lee.
• Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex.
• J. Thorac. Cardiovasc. Surg. 2024 Oct 10.

BackgroundImmune 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.MethodsWe 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.ResultsSeventy-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.ConclusionsSMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

6 keywords...

hide…