Soluble Mesothelin-Related Peptide as a Prognosticator in Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy. Soluble Mesothelin-Related Peptide as a Prognosticator in Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy

Objective: Immune checkpoint therapy (ICT) has significantly impacted malignant pleural mesothelioma (MPM) treatment. 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. Results: Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, while the remaining 38% were given combination ICT. Higher pre-ICT SMRP levels were notably observed in epithelioid versus non-epithelioid MPM. Serum PD-L1 levels did not show significant differences between the groups. Univariable analysis identified durable clinical benefits, 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 (median survival: 23 months vs. 13 months). This finding was further validated in the prospective ICT clinical trial cohort. Conclusions: SMRP emerges as a promising serum biomarker for predicting survival in MPM patients treated with ICT, warranting further prospective investigation. Overall design: Methods: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1 using the MESOMARK and Luminex assays, respectively. We also examined the correlation of these serum levels with tumor mRNA expressions of MSLN 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.

研究背景与目的：免疫检查点治疗（immune checkpoint therapy, ICT）对恶性胸膜间皮瘤（malignant pleural mesothelioma, MPM）的临床治疗具有重要影响。尽管联合治疗方案已取得部分可喜成果，但仍有近半数MPM患者无法从中获益，这凸显了开发可靠预测性生物标志物的迫切需求。本研究旨在评估血清可溶性间皮素相关肽（serum soluble mesothelin-related peptide, SMRP）与PD-L1水平在接受ICT治疗的MPM患者中的预后价值。
研究结果：本研究共纳入125例MPM患者，其中77例（62%）接受抗PD-(L)1单药治疗，剩余38%接受联合ICT治疗。相较于非上皮样MPM，上皮样MPM患者的ICT治疗前血清SMRP水平显著升高；而血清PD-L1水平在两组间未表现出显著差异。单因素分析显示，持续临床获益、免疫相关不良事件的发生以及SMRP水平均与总生存期（overall survival, OS）显著相关。多因素分析证实，SMRP是独立的预后因素：当SMRP水平≤1.35 nmol/L时，患者的总生存期更优（中位生存期：23个月 vs 13个月）。这一结论在一项前瞻性ICT临床试验队列中得到了进一步验证。
研究结论：SMRP有望成为预测接受ICT治疗的MPM患者生存结局的潜在血清生物标志物，有待开展进一步的前瞻性研究加以验证。
整体研究设计与方法：我们对125例接受ICT治疗的MPM患者开展回顾性分析，分别采用MESOMARK检测与Luminex检测技术，测定患者接受ICT治疗前的血清SMRP与PD-L1水平。同时分析了上述血清水平与肿瘤MSLN及PD-L1的mRNA表达水平的相关性。采用单因素及多因素Cox回归分析，明确与总生存期相关的独立预后因素。本研究通过一项前瞻性ICT临床试验队列及本中心的历史队列对研究结果进行验证。