On June 3, 2019 NantWorks, LLC reported that its affiliate companies, NantHealth, Inc., (NASDAQ: NH), a leading next-generation, evidence-based, personalized healthcare company, and NantOmics, LLC, the leader in molecular analyses , will present data on the association between increased TMB and increased PD-L1 expression with the presence of SDH/FH mutations in a variety of tumors, using 3,461 paired tumor/normal whole exome sequences from the NantHealth clinical cases database to look into the potential therapeutic role for inhibition of PD-1/PD-L1 pathway in these tumors during the cancer prevention, hereditary genetics and epidemiology session at the ASCO (Free ASCO Whitepaper) 2019 Annual Meeting, an event bringing together more than 32,000 global oncology professionals from May 31-June 4, 2019 at McCormick Place in Chicago, Illinois (Press release, NantHealth, JUN 3, 2019, View Source [SID1234536828]). NantHealth and NantOmics conducted this study with researchers from Virginia Commonwealth University’s Massey Cancer Center. NantWorks will be exhibiting at booth #24080 during the event.
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"We believe the data from our retrospective analysis may impact the use of immunotherapy for SDH/FH deficient tumors," said Sandeep "Bobby" Reddy, MD, Chief Medical Officer, NantHealth. "Our analysis provides actionable insight and evidence-based support to further our mission of optimizing patient outcomes and enabling value-based care, specifically in the oncology realm."
Presentation Details
Tumor mutation burden and PD-L1 expression in SDH/FH mutated solid tumors, Abstract #1524
WHO:NantHealth, Inc. and NantOmics, LLC
WHAT: Cancer Prevention, Hereditary Genetics and Epidemiology Session
WHEN:June 3, 1:15-4:15 PM CDT
WHERE: Hall A, McCormick Place
Presentation Summary
Succinate Dehydrogenases and Fumarate Hydratase (SDH/FH) deficient tumors are characterized by succinate/fumarate accumulation and resultant pseudohypoxia that drives malignant transformation. It has been recently shown that HIF-1a stabilization due to hypoxia can lead to upregulation of PD-1 ligand. This study explored tumor mutation burden (TMB), gene expression of PD-L1 and expression of other immune checkpoint-associated genes in a diverse cohort of human tumors harboring SDH A, B, C, D and FH mutations. Retrospective analysis was performed on 3,461 paired tumor/normal whole exome sequences (WES; ~150x coverage) from the NantHealth clinical cases database. 42 clinical cases with potentially pathogenic variants (pPV) in SDHx and FH were identified. Variant pathogenicity was assessed by multiple factors including driver gene status, variant class (e.g. Missense), PhastCons conservation score and population allele frequency. The study found an association between increased TMB and increased PD-L1 expression with the presence of SDH/FH mutations in a variety of tumors. These key parameters imply that a higher TMB may drive the evolutionary pressure to select clones with a PD-L1 high phenotype. This observation supports a potential therapeutic role for inhibition of PD-1/PD-L1 pathway in these tumors.