immune report card

You can DO BETTER than Immunohistochemistry (IHC)


The positive and negative predictive value of PD-L1 IHC is too low

  • The DAKO pharmDx 22C3 IHC assay identifies 25% of all patients eligible for treatment as responders, of which only ~42% of treated patients respond (10% of eligible population)1
  • Using a threshold of 5% as PD-L1 IHC positive, 15% of PD-L1-positive and 14% PD-L1 negative advanced non-small-cell lung cancer patients respond to Nivolumab2

IHC does not have sufficiently dynamic range

  • In order to compare expression levels relative to a reference population,,measurement of multiple messenger RNAs is more robust than IHC3
  • PD-L1 is part of a complex pathway, requiring measurement of co-stimulated molecules for a complete assessment of the underlying biology

IHC may use too much sample to scale across multiple immunotherapy markers

  • As additional assays are required, IHC will require more tissue, which may require additional biopsies
  • IHC costs are linear as incremental markers are added. By contrast, incremental costs for adding content to next generation sequencing are nominal

IHC is not reproducible across antibodies and scoring pathologists

  • Discordance between PD-L1 clinical expression levels across PD-L1 IHC assays: 37% of cases showed discordance between PD-L1 clinical expression levels4
  • CTLA4 does not currently have a companion diagnostic IHC assay5

To learn more about Immune Report Card visit the IRC page or call (800) 781-1259

1. Garon, Edward B., et al. “Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer.” New England Journal of Medicine 372.21(2015): 2018-028. Web.
2. Gettinger, Scott, and Roy S. Herbst. “B7-H1/PD-1 Blockade Therapy in Non-Small Cell Lung Cancer.” The Cancer Journal 20.4 (2014): 281-89. Web.
3. Paluch, Benjamin E., et al. “Robust detection of immune transcripts in FFPE samples using targeted RNA sequencing.” Oncotarget (2016): n. pag. Web.
4. Hirsch, Fred R., et. al.”PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project.”
Journal of Thoracic Oncology 12.2 (2017): 208-22. Web.
5. Warren, Sarah E., et al. “Next Generation Diagnostics for Immuno-Oncology.” Targeted Oncology July 07, 2016. Web.