Oncotarget | Site of analysis matters – Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation

News, Oncotarget

September 29, 2022
Research Article

“This case report represents an HIV infected patient with anal cancer, MSI high status, a high mutation frequency regarding tumor mutational burden (TMB), and an ongoing response to Nivolumab.”

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BUFFALO, NY- September 29, 2022 – A new research paper was published in Oncotarget’s Volume 13 on September 14, 2022, entitled, “Site of analysis matters – Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation.”

Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease, which cannot be treated with chemoradiotherapy or salvage surgery, systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy, programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging, including in patients with anal cancer. 

“Altogether, there is little data on PD-1 treatment in HIV infected patients.”

In a new study, researchers Melanie Demes, Ursula Pession, Jan Jeroch, Falko Schulze, Katrin Eichler, Daniel Martin, Peter Wild, and Oliver Waidmann from Universitätsklinikum Frankfurt and Centrum für Hämatologie und Onkologie reported a case of an HIV infected patient with anal cancer, microsatellite instability (MSI) high status, a high mutation frequency regarding tumor mutational burden (TMB) and an ongoing response to Nivolumab. 

“We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment.”

Thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. The researchers concluded that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor.

“According to our results, we propose to assess mutational status in tissue from metastasis rather than from the primary site when additional molecular analyses are performed for treatment decisions.”

DOI: https://doi.org/10.18632/oncotarget.28274

Correspondence to: Oliver Waidmann – Emails: oliver.waidmann@kgu.de 

Keywords: anal cancer, microsatellite instability, immunotherapy, high-throughput nucleotide sequencing, nivolumab

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