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Potential Predictive Markers and/or Therapeutic Targets in Merkel Cell Carcinoma

By: Vanessa A. Carter, BS
Posted: Friday, December 11, 2020

Immunotherapy for patients with Merkel cell carcinoma is not always effective since potential predictive biomarkers and molecular mechanisms related to the disease are not fully understood. At the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 306), Glenn Hanna, MD, of Dana-Farber Cancer Institute, Boston, and colleagues presented their insight on clinical and genomic factors that may be at play in patients’ response to immunotherapy. Their work was also published in the Journal for ImmunoTherapy of Cancer.

“Patients with shorter disease-free intervals after definitive treatment may be particularly suitable candidates for immunotherapy,” the researchers stated. “Our molecular findings point to ARID2 and NTRK1 as potential predictive markers and/or therapeutic targets, although this association needs to be confirmed in a larger sample.”

The data from a total of 45 patients with stage III disease at diagnosis and stage IV disease at the time of diagnosis of metastatic or recurrent disease were collected. The gathered information included patients’ electronic health record, provider notes, and the researchers’ institutional next-generation sequencing panel of actionable genomic alterations.

The median overall survival was 15.5 months, and 43% of participants experienced an objective response to immunotherapy. The response was correlated with single-nucleotide variants in the NTRK1 and ARID2 genes. Among the sequenced cohort, TP53 (59%) and RB1 (51%) were the most common single-nucleotide variants. Greater odds of response were associated with lower stage at diagnosis and shorter disease-free interval between completion of initial treatment and recurrence. None of the Merkel cell total mutational burden, copy-number alterations, ultraviolet mutational signatures, or polyomavirus status predicted any outcomes.

Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.



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