Characterizing the Genome in Merkel Cell Carcinoma
Posted: Tuesday, September 17, 2019
Researchers from the Moffitt Cancer Center and Research Institute in Tampa, Florida, have developed a comprehensive genomic landscape for Merkel cell carcinoma and were able to provide clinicogenomic associations with immunotherapy response. Todd C. Knepper, PharmD, and colleagues published their work in Clinical Cancer Research.
“Recently, the treatment paradigm for advanced Merkel cell carcinoma has shifted dramatically, with immune checkpoint inhibitors demonstrating remarkable efficacy in this disease,” said Dr. Knepper in a Moffitt press release. “Clinical data have demonstrated their ability to improve patient response rates and survival.”
To generate their data, researchers performed comprehensive molecular profiling on 317 patients with Merkel cell carcinoma. They looked at oncogenic mutations, tumor mutational burden (TMB), mutational signatures, and the Merkel cell polyomavirus. Retrospective analysis was performed on 57 patients to assess clinical and molecular correlates to immune checkpoint inhibitor response and disease survival.
Two distinct populations were identified from the sample: one with a high TMB and one with a low TMB. About 94% of patients with a high TMB had an ultraviolet signature mutation in their tumor DNA, and none of these patients were found to have the Merkel cell polyomavirus. In contrast, patients with a low TMB did not have ultraviolet signature mutations, and 63% of these patients had evidence of Merkel cell polyomavirus in their tumors.
Further analysis led to the discovery that immunotherapies were effective in patients with a high and a low TMB, as 50% of patients with a high TMB and 41% of patients with a low TMB responded to therapy. When immunotherapy was given as a first-line treatment, patients had a 75% response rate, compared with 39% in the second-line setting and 18% in the third-line setting. In addition, patients expressing the PD-1 biomarker seemed to have a better response to immunotherapy than those who did not express PD-1.
Disclosure: The study authors’ disclosure information can be found at clincancerres.aacrjournals.org.
