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Alfred Zippelius



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    Lunch & Poster Display session (ID 58)

    • Event: ELCC 2019
    • Type: Poster Display session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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      161P - Tumor mutational burden assessed by a targeted NGS assay predicts clinical benefit from immune checkpoint inhibitors in non-small cell lung cancer (ID 556)

      12:30 - 13:00  |  Author(s): Alfred Zippelius

      • Abstract
      • Slides

      Background

      In non-small cell lung cancer (NSCLC) immune checkpoint inhibitors (ICIs) significantly improve progression-free survival (PFS) and objective response rate. Biomarkers capable of predicting response to ICIs are highly desired. Assessment of tumor mutational burden (TMB) by whole-exome sequencing has been associated with outcome in patients treated with ICIs. Recently, being more suited for clinical applications, targeted sequencing has also proven its ability to reliably assess TMB. Our study is the first to evaluate the predictive power of TMB measured through the Oncomine Tumor Mutational Load (TML - Thermo Fisher Scientific) assay in 64 NSCLC patients treated with ICIs.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      TMB was assessed retrospectively in patients with metastatic NSCLC exposed to ICIs. Clinical data (RECIST 1.1) were collected and patients were characterized as either having clinical benefit (CB = complete/partial response (CR/PR) or stable disease (SD)) or having no clinical benefit. TMB was assessed using the TML assay, covering 409 genes. Differences in TMB between responders and non-responders were examined using Mann-Whitney test.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      TMB assessed by the TML assay was significantly higher in patients with CB compared to patients with no CB (median TMB = 5.9 versus 8.4 mutations/Mb, Mann-Whitney p = 0.028). TMB predicts CB by receiver operating characteristic (ROC, AUC = 0.66). 67% of patients with high TMB (cutoff = 3rd tertile, TMB = 8.7) were responders (CB), compared to only 24% of patients with low TMB (cutoff = 1st tertile, TMB = 5). TMB-high patients were characterized by a significantly higher progression-free survival (PFS) compared to patients with low mutational load (log rank for trend, p = 0.024). Finally, the highest response rate was observed in PD-L1 positive samples with high tumor mutational load (73%), whereas the PD-L1 negative and TMB-low population consisted of only 11% responders.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Our results show that the TML panel is an effective tool for patient stratification for ICI treatment. Since we observed the highest response rate in PD-L1 positive patients with a high mutational load, we believe that a combinatorial use of biomarkers will maximize the precision of patient selection.

      b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study

      University Hospital Basel.

      213f68309caaa4ccc14d5f99789640ad Funding

      Bristol-Myers Squibb, Thermo Fisher Scientific.

      682889d0a1d3b50267a69346a750433d Disclosure

      P. Jermann: Bristol-Myers Squibb provides funding in the form of a research grant. Thermo Fisher Scientific provides next-generation sequencing reagents and access to analysis software and technical support. All other authors have declared no conflicts of interest.

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