Dr. Weber on Biomarker Data From CheckMate-238 for Melanoma

Jeffrey S. Weber, MD, PhD
Published: Wednesday, Nov 06, 2019



Jeffrey S. Weber, MD, PhD, deputy director and co-director of the Melanoma Program, NYU Langone’s Perlmutter Cancer Center, 2016 Giant of Cancer Care® in Melanoma, discusses biomarker research in the CheckMate-238 trial looking at patients with resected stage III/IV melanoma.

For the first time, researchers collected biomarker data from a significant portion of patients from the CheckMate-238 trial. Researchers looked at 3 tumor-related biomarkers: tumor mutational burden (TMB) by whole-exome sequencing, interferon-gamma–induced genes by shotgun sequencing, and CD8+ T-cell infiltrate by histochemistry, explains Weber.

Additionally, for the first time there was a peripheral blood marker consisting of monocytic myeloid-derived suppressor cells (MDSC) in the peripheral blood by flow cytometry, according to Weber. The tumor markers are above the median for peripheral blood suppressive marker, showing a clear association with outcome for the nivolumab (Opdivo) and ipilimumab (Yervoy) arms, says Weber. The most potent biomarkers with the best hazard ratios were the interferon-gamma–induced genes and TMB.

In combinations of typically independent biomarkers, elevation in TMB above the median, elevation of the interferon-gamma–induced genes above the median, or depression of MDSC resulted in a better hazard ratio for outcome, Weber concludes.
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Jeffrey S. Weber, MD, PhD, deputy director and co-director of the Melanoma Program, NYU Langone’s Perlmutter Cancer Center, 2016 Giant of Cancer Care® in Melanoma, discusses biomarker research in the CheckMate-238 trial looking at patients with resected stage III/IV melanoma.

For the first time, researchers collected biomarker data from a significant portion of patients from the CheckMate-238 trial. Researchers looked at 3 tumor-related biomarkers: tumor mutational burden (TMB) by whole-exome sequencing, interferon-gamma–induced genes by shotgun sequencing, and CD8+ T-cell infiltrate by histochemistry, explains Weber.

Additionally, for the first time there was a peripheral blood marker consisting of monocytic myeloid-derived suppressor cells (MDSC) in the peripheral blood by flow cytometry, according to Weber. The tumor markers are above the median for peripheral blood suppressive marker, showing a clear association with outcome for the nivolumab (Opdivo) and ipilimumab (Yervoy) arms, says Weber. The most potent biomarkers with the best hazard ratios were the interferon-gamma–induced genes and TMB.

In combinations of typically independent biomarkers, elevation in TMB above the median, elevation of the interferon-gamma–induced genes above the median, or depression of MDSC resulted in a better hazard ratio for outcome, Weber concludes.



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