Reference Medicine collaborates to publish work in Merkel Cell Carcinoma in journal, Cancers
Oct 20, 2023
Reference Medicine contributes to meaningful research into the relationship of biomarker expression and the response to immune checkpoint inhibitors in MCC.
As published in Cancers 2023, 15(20), 5084
An Updated Review of the Biomarkers of Response to Immune Checkpoint Inhibitors in Merkel Cell Carcinoma: Merkel Cell Carcinoma and Immunotherapy
by Adnan Fojnica 1,2, Kenana Ljuca3, Saghir Akhtar4, Zoran Gatalica5,6 and Semir Vranic4,
- 1Institute of Virology, TUM School of Medicine, Technical University of Munich, 81675 Munich, Germany
- 2Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8036 Graz, Austria
- 3Health Center of Sarajevo Canton, 71000 Sarajevo, Bosnia and Herzegovina
- 4Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha 2713, Qatar
- 5Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73019, USA
- 6Reference Medicine, Phoenix, AZ 85040, USA
Simple Summary
Merkel cell carcinoma (MCC) is a rare and highly aggressive type of skin neuroendocrine cancer that frequently recurs and metastasizes within a relatively short period. Despite rapid growth and characteristic skin color, MCC often goes undiagnosed in its early stage. Therefore, therapy is often initiated at the advanced stage, and selecting appropriate therapeutic interventions is critical. The emergence of novel immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), presents a promising treatment option for advanced MCC. Several biomarkers, such as PD-L1 expression, tumor mutational burden (TMB), and microsatellite instability (MSI), showed significant potential as predictive biomarkers for treatment with ICI. Despite their predictive value, each has demonstrated limited value in MCC over recent years.
Abstract
Merkel cell carcinoma (MCC) is primarily a disease of the elderly Caucasian, with most cases occurring in individuals over 50. Immune checkpoint inhibitors (ICI) treatment has shown promising results in MCC patients. Although ~34% of MCC patients are expected to exhibit at least one of the predictive biomarkers (PD-L1, high tumor mutational burden/TMB-H/, and microsatellite instability), their clinical significance in MCC is not fully understood. PD-L1 expression has been variably described in MCC, but its predictive value has not been established yet. Our literature survey indicates conflicting results regarding the predictive value of TMB in ICI therapy for MCC. Avelumab therapy has shown promising results in Merkel cell polyomavirus (MCPyV)-negative MCC patients with TMB-H, while pembrolizumab therapy has shown better response in patients with low TMB. A study evaluating neoadjuvant nivolumab therapy found no significant difference in treatment response between the tumor etiologies and TMB levels. In addition to ICI therapy, other treatments that induce apoptosis, such as milademetan, have demonstrated positive responses in MCPyV-positive MCC, with few somatic mutations and wild-type TP53. This review summarizes current knowledge and discusses emerging and potentially predictive biomarkers for MCC therapy with ICI.
