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.

Related Videos
An expert from Weill Cornell Medicine highlights key clinical data indicating the benefits of radium-223 in the treatment of patients with metastatic castration-resistant prostate cancer.
The risk of radionuclide exposure to the public reflects one reason urologists need to collaborate with radiation oncologists when administering radiopharmaceuticals to patients with prostate cancer.
Switching out beta emitters for alpha emitters, including radium-223, is one way to improve radiopharmaceutical treatment of prostate cancer, according to an expert from Weill Cornell Medicine.
Data demonstrate the feasibility of automated glomerular filtration rate prediction to decide between partial nephrectomy and radical nephrectomy in kidney cancer, according to an expert from the Cleveland Clinic.
Early phase trials investigating cellular therapies, bispecific antibodies, and antibody-drug conjugates for refractory kidney cancer may uncover strategies to overcome resistance mechanisms.
Increasing cancer antigen presentation as well as working with tumor cells in and delivering novel cells to the microenvironment may help in overcoming mechanisms of immune checkpoint inhibitor resistance in refractory renal cell carcinoma.
Lenvatinib plus pembrolizumab appears to be the best option for patients with refractory metastatic renal cell carcinoma who are progressing on immunotherapy combinations or are lenvatinib naïve.
Ipilimumab monotherapy does not appear effective in driving complete responses in refractory renal cell carcinoma despite yielding some progression-free survival intervals, according to an expert from the University of Texas Southwestern Medical Center.
An expert from the University of Texas Southwestern Medical Center discusses several phase 3 clinical trials supporting the use of various single-agent and combination immunotherapy regimens for advanced kidney cancer.
Shilpa Gupta, MD, shares the current standard of care for muscle-invasive bladder cancer and highlights other options that may be suitable for some patients.
Related Content