Format

Send to

Choose Destination
JCO Precis Oncol. 2018;2018. doi: 10.1200/PO.17.00282. Epub 2018 May 11.

Megakaryocyte Potentiating Factor as a Predictive Biomarker for Therapies Against Malignant Mesothelioma.

Author information

1
National Cancer Institute, Bethesda, MD.
#
Contributed equally

Abstract

Purpose:

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.

Materials and Methods:

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.

Results:

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 (P < .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.

Conclusion:

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.

Conflict of interest statement

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Liang Cao No relationship to disclose Yunkai Yu No relationship to disclose Anish Thomas No relationship to disclose Jingli Zhang No relationship to disclose Masanori Onda No relationship to disclose Paul Meltzer Research Funding: Genzyme (Inst) Raffit Hassan Research Funding: Aduro Biotech (Inst), Morphotek (Inst), Bayer (Inst) Ira Pastan No relationship to disclose

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center