• Media type: E-Article
  • Title: Complete Metabolic Response to Combined Immune Checkpoint Inhibition after Progression of Metastatic Colorectal Cancer on Pembrolizumab: A Case Report
  • Contributor: Krekeler, Carolin; Wethmar, Klaus; Mikesch, Jan-Henrik; Kerkhoff, Andrea; Menck, Kerstin; Lenz, Georg; Schildhaus, Hans-Ulrich; Wessolly, Michael; Hoffmann, Matthias W.; Pascher, Andreas; Asmus, Inga; Wardelmann, Eva; Bleckmann, Annalen
  • Published: MDPI AG, 2023
  • Published in: International Journal of Molecular Sciences, 24 (2023) 15, Seite 12056
  • Language: English
  • DOI: 10.3390/ijms241512056
  • ISSN: 1422-0067
  • Keywords: Inorganic Chemistry ; Organic Chemistry ; Physical and Theoretical Chemistry ; Computer Science Applications ; Spectroscopy ; Molecular Biology ; General Medicine ; Catalysis
  • Origination:
  • Footnote:
  • Description: DNA mismatch repair deficient (dMMR) and microsatellite instable (MSI) metastatic colorectal cancer (mCRC) can be successfully treated with FDA- and EMA-approved immune checkpoint inhibitors (ICI) pembrolizumab and nivolumab (as single agents targeting the anti-programmed cell death protein-1 (PD-1)) or combinations of a PD-1 inhibitor with ipilimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-targeting antibody. The best treatment strategy beyond progression on single-agent ICI therapy remains unclear. Here, we present the case of a 63-year-old male with Lynch-syndrome-associated, microsatellite instability-high (MSI-H) mCRC who achieved a rapid normalization of his tumor markers and a complete metabolic remission (CMR), currently lasting for ten months, on sequential ICI treatment with the combination of nivolumab and ipilimumab followed by nivolumab maintenance therapy after progression on single-agent anti-PD-1 ICI therapy. The therapy was well-tolerated, and no immune-related adverse events occurred. To the best of our knowledge, this is the first case of a sustained metabolic complete remission in an MSI-H mCRC patient initially progressing on single-agent anti-PD-1 therapy. Thus, dMMR mCRC patients might benefit from sequential immune checkpoint regimens even with long-term responses. However, further sophistication of clinical algorithms for treatment beyond progression on single-agent ICI therapy in MSI-mCRC is urgently needed.
  • Access State: Open Access