Investigators on the Rationale for Exploring Sex Bias Related to TMB as a Biomarker of PD-1 Inhibitors

CancerNetwork® spoke with Neelam and Sanju Sinha of the National Cancer Institute about their research into sex differences associated with using tumor mutational burden to predict response to PD-1 inhibition.

CancerNetwork® sat down with Neelam and Sanju Sinha, sibling investigators who work with computational biologist Eytan Ruppin, MD, PhD, at the National Cancer Institute, to discuss their abstract presented at the recent American Association for Cancer Research (AACR) Annual Meeting 2021 on tumor mutational burden (TMB) as a biomarker for PD-1 inhibition. They set out to determine if sex affected that strength of immune selection, biomarkers of outcome, TMB levels, and response to immunotherapy.


N. Sinha: Last year, the FDA had approved…tumor mutation burden [as a biomarker] for all patients with solid tumors who were treated with anti–PD-1, or pembrolizumab [Keytruda]. Also, from recent studies and prior knowledge, we were aware that the strength of immune selection, TMB levels, and the response to PD-1 immunotherapy is different between male and female patients. We hypothesized, or we asked this question, using the single threshold of tumor mutation burden [at 10 mutations per megabase, can we show] sex bias between the patients. So, from here, we started our study.

S. Sinha: We primarily asked whether there is any difference in survival between males and females between the 2 groups of low-TMB versus high-TMB. When these 2 groups are divided using the threshold, which Neelam just described at 10 mutation per megabase, we asked whether there is any difference between these 2 groups and whether this difference is dependent upon the sex of the patients.


Sinha N, Sinha S, Cheng K, et al. The recently approved high-TMB criteria may introduce a sex bias in response to PD1 inhibitors. Presented at: AACR Annual Meeting 2021; April 10-15, 2021; virtual. Abstract 29.