Cao Liang, Yu Yunkai, Thomas Anish, Zhang Jingli, Onda Masanori, Meltzer Paul, Hassan Raffit, Pastan Ira
National Cancer Institute, Bethesda, MD.
JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.17.00282. Epub 2018 May 11.
Effective biomarkers for malignant mesothelioma (MM) are needed for clinical management and the development of mesothelin-targeted therapies. We evaluated serum megakaryocyte potentiating factor (MPF) as a biomarker predictive of treatment outcome in patients with MM and for developing mesothelin-targeted therapies.
Serial serum samples from patients with MM in two clinical trials of an antimesothelin immunotoxin were tested with our clinically validated MPF assay. Correlative studies were performed to determine the test effectiveness in treatment monitoring and outcome prediction. MPF was further evaluated for an association with response to an antimesothelin therapy and for disease monitoring.
There was a significant reduction of serum MPF in patients with elevated baseline and radiologic response, with an average change from -52% to -78% after one to six cycles. Using a -50% change as the cutoff, patients with MM with positive MPF response had significantly improved progression-free survival ( < .001), with the median extended from 1.9 to 11.3 months. These patients with MPF response further exhibited improved overall survival (P = .004), with the median extended from 8.8 to 22.3 months. In patients with refractory MM, there was an association between elevated pretreatment serum MPF and radiologic response to an antimesothelin therapy (P = .033). Furthermore, in these response patients, serum MPF was monitored between 32.2 and 63.8 months and was found to reflect treatment response and disease progression.
At a cutoff of -50% change after receiving systemic therapies, a reduction in MPF was associated with improved clinical outcome, both progression-free survival and overall survival. An elevated baseline serum MPF was associated with a response to an antimesothelin therapy in patients with refractory MM; however, this finding needs to be confirmed in another study.
恶性间皮瘤（MM）的有效生物标志物对于临床管理和间皮素靶向治疗的开发至关重要。我们评估了血清巨核细胞增强因子（MPF）作为预测MM患者治疗结果以及开发间皮素靶向治疗的生物标志物。
在一项抗间皮素免疫毒素的两项临床试验中，对MM患者的系列血清样本进行了我们经过临床验证的MPF检测。进行相关性研究以确定该检测在治疗监测和结果预测中的有效性。进一步评估MPF与抗间皮素治疗反应的相关性以及疾病监测情况。
基线升高且有放射学反应的患者血清MPF显著降低，在一至六个周期后平均变化从-52%至-78%。以-50%的变化作为临界值，MPF反应呈阳性的MM患者无进展生存期显著改善（P<0.001），中位数从1.9个月延长至11.3个月。这些有MPF反应的患者总生存期也有所改善（P = 0.004），中位数从8.8个月延长至22.3个月。在难治性MM患者中，治疗前血清MPF升高与抗间皮素治疗的放射学反应之间存在关联（P = 0.033）。此外，在这些有反应的患者中，血清MPF在32.2至63.8个月期间进行监测，发现其反映了治疗反应和疾病进展。
在接受全身治疗后变化临界值为-50%时，MPF降低与无进展生存期和总生存期等临床结果改善相关。难治性MM患者基线血清MPF升高与抗间皮素治疗反应相关；然而，这一发现需要在另一项研究中得到证实。
