Site of analysis matters - Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation
Metrics: PDF 90 views | Full Text 1149 views | ?
Melanie Demes1,2, Ursula Pession2,3, Jan Jeroch1, Falko Schulze1,2, Katrin Eichler2,4, Daniel Martin2,5, Peter Wild1,2 and Oliver Waidmann2,6,7
1 Dr. Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
2 Universitäres Centrum für Tumorerkrankungen (UCT), Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
3 Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
4 Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
5 Klinik für Strahlentherapie und Onkologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
6 Medizinische Klinik 1, Schwerpunkte Gastroenterologie und Hepatologie, Universitätsklinikum Frankfurt, Frankfurt 60590, Germany
7 Centrum für Hämatologie und Onkologie, Frankfurt 60389, Germany
Keywords: anal cancer; microsatellite instability; immunotherapy; high-throughput nucleotide sequencing; nivolumab
Received: September 11, 2021 Accepted: September 05, 2022 Published: September 14, 2022
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 anal cancer. 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. Namely, 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. Therefore, we conclude 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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.