Mitra Sonali, Jang Hee-Jin, Kuncheria Allen, Kang Sung Wook, Choi Jong Min, Shim Ji Seon, Lee Claire, Ranchod Priyanka, Jindra Peter, Ramineni Maheshwari, Patel Meera, Ripley R Taylor, Groth Shawn S, Blackmon Shanda H, Burt Bryan M, Lee Hyun-Sung
Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex.
Immune Evaluation Laboratory, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex.
J Thorac Cardiovasc Surg. 2025 Apr;169(4):1082-1095.e4. doi: 10.1016/j.jtcvs.2024.10.005. Epub 2024 Oct 10.
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.
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.
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.
SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.
免疫检查点疗法（ICT）对恶性胸膜间皮瘤（MPM）的治疗产生了重大影响。尽管联合疗法取得了一些令人鼓舞的结果，但近一半的MPM患者并未从中受益，这凸显了对可靠预测生物标志物的迫切需求。本研究评估了接受ICT的MPM患者血清可溶性间皮素相关肽（SMRP）和PD-L1水平的预后价值。
我们对125例接受ICT治疗的MPM患者进行了回顾性分析，测量了ICT治疗前血清SMRP和PD-L1水平。我们还研究了这些血清水平与间皮素和PD-L1肿瘤mRNA表达的相关性。采用单变量和多变量Cox回归分析来确定总生存期（OS）的独立预后因素。纳入一项前瞻性ICT临床试验和我们的历史队列进行验证。
77例患者（62%）接受了抗PD-(L)1单药治疗，其余38%接受了联合ICT治疗。与非上皮样MPM相比，上皮样MPM患者ICT治疗前SMRP水平更高。不同组织学组之间血清PD-L1水平无显著差异。单变量分析确定持久的临床获益、免疫相关不良事件的发生以及SMRP水平与OS显著相关。多变量分析证实SMRP是一个独立的预后因素，较低水平（≤1.35 nmol/L）与OS改善相关。高SMRP与较差预后的关联在前瞻性ICT临床试验队列中得到验证，而在未接受ICT治疗的历史队列中未得到验证。
SMRP是预测接受ICT治疗的MPM患者生存的一种有前景的血清生物标志物，值得进行前瞻性研究。
