Bespoke circulating tumor DNA as a biomarker for treatment response in a refractory Merkel cell carcinoma patient

Merkelcell.org Summary

This case report showed that a personalized and tumor-informed (‘bespoke’) test for cell-free circulating tumor DNA (ctDNA) could predict MCC treatment response in an MCC patient treated with Talimogene laherparepvec (T-VEC) and hypofractionated radiation (HRT).

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with climbing incidence and a dismal 5-year survival rate ≤18%.1 While immune checkpoint inhibitors (ICIs) have become standard of care for advanced MCC,2 there is no effective alternative for patients ineligible or resistant to immunotherapy. Thus, there is a clinical demand for sensitive biomarker(s) to gauge the response to ICIs and beyond.

Talimogene laherparepvec (T-VEC) is a modified oncolytic herpes simplex virus expressing granulocyte-macrophage colony-stimulating factor promoting a local and systemic antitumor immune response.3 As hypofractionated radiation (HRT) is more immunogenic than conventional radiation,4 there is a strong rationale to combine T-VEC and HRT, especially in MCCs progressed on ICIs.

Cell-free circulating tumor DNA (ctDNA) has emerged as an important tool for monitoring molecular residual disease (MRD), owing to its minimal invasiveness and high concordance between genetic alternations detected in tumor and ctDNA.5 Recent studies show that ctDNA is sensitive and effective in postoperative management, early detection of relapse, and prediction of treatment response in several human cancers.6, 7, 8, 9 In this pilot observation, we first demonstrate that a personalized and tumor-informed (bespoke) ctDNA assay is predictive of MCC treatment response. Moreover, combinatorial T-VEC and HRT is an effective alternative for an MCC patient progressed on pembrolizumab.