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

Oncotarget. 2022 Sep 14:13:1034-1042. doi: 10.18632/oncotarget.28274. eCollection 2022.

Abstract

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.

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

Publication types

  • Case Reports

MeSH terms

  • Anus Neoplasms* / drug therapy
  • Anus Neoplasms* / genetics
  • Carboplatin
  • HIV Infections*
  • Humans
  • Microsatellite Instability
  • MutL Protein Homolog 1 / genetics
  • Mutation
  • Nivolumab / therapeutic use
  • Paclitaxel
  • Papillomavirus Infections*
  • Programmed Cell Death 1 Receptor

Substances

  • MLH1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • Carboplatin
  • MutL Protein Homolog 1
  • Paclitaxel

Supplementary concepts

  • Anal Canal Carcinoma