Home Prostate / Prostate Cancer High Tumor Mutation Burden Predicts Response to Immune Checkpoint Blockade for Some...

High Tumor Mutation Burden Predicts Response to Immune Checkpoint Blockade for Some Cancer Types

58
0

A study investigating the predictive capabilities of high tumor mutation burden (TMB) found it was predictive of clinical responses to immune checkpoint inhibitors for a subset of cancer types, according to data published in Annals of Oncology.1

Even though TMB status was able to successfully predict the response to immune checkpoint blockade (ICB) in some cancers—such as lung cancers, bladder cancers, and melanoma—it was unsuccessful in predicting response in cancers such as breast cancers, prostate cancers, and brain cancers.

“This study represents the most comprehensive analysis to date of TMB as a biomarker for response to immune checkpoint blockade,” lead author Daniel J. McGrail, PhD, postdoctoral fellow in Systems Biology, said in a press release.2 “Our results do not support applying high TMB status as a universal biomarker for immunotherapy response, suggesting that additional tumor type–specific studies are needed to clarify how best to apply TMB status in cancer types where it does not appear to be associated with outcomes.”

When focusing on cancer types where CD8 T-cell levels positively correlated with neoantigen load, including lung cancers, bladder cancers, and melanoma, these data found that high TMB tumors exhibited a 39.8% overall response rate (ORR) to ICB (95% CI, 34.9-44.8). The almost 40% ORR was significantly higher than that of low TMB tumors (odds ration [OR], 4.1; 95% CI, 2.9-5.8; P <2 × 10-16).

For the cancer types with no observable relationship between CD8 T-cell levels and neoantigen load, including breast cancers, prostate cancers, and brain cancers, high TMB tumors achieved an ORR of 15.3% (95% CI, 9.2%-23.4%; P = .95), which was significantly lower relative to TMB-low tumors (OR, 0.46; 95% CI, 0.24-0.88; P = .02).

The research team noted that bulk ORRs were not significantly different between the 2 tumor categories (P = .10), and equivalent data were produced by analyzing overall survival and treating TMB as a continuous variable.

“While TMB-H demonstrates promise as a predictive biomarker for patient selection for ICB treatment, our analysis fails to support the hypothesis that a single TMB threshold can identify patients in a pan-cancer fashion who may benefit from ICB,” wrote the investigators.

Data from The Cancer Genome Atlas focusing on over 10,000 tumors across 31 cancer types was used to identify the correlation between CD8 T cells and predicted neoantigen load. The primary measures for the association of TMB with ICB treatment outcomes were ORR and overall survival.

The research team wrote that the retrospective design of the study limited the data to various DNA sequencing approaches. More, the variations among the immune checkpoint inhibitors and clinical outcomes reported across different patient cohorts played a role in limiting the data.

“Current evidence fails to support the use of TMB-H as a biomarker for ICB treatment in all tumor types, including the FDA-approved threshold of 10 [mutations per megabase],” wrote the investigators. “Future studies should focus both on improving cancer type–specific assessment of TMB from targeted sequencing and cancer type–specific activity of ICB in TMB-H tumors before broad clinical implementation.”

References:

1. McGrail DJ, Pilie PG, Rashid NU, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types. Ann Oncol. Published online March 15, 2021. doi:10.1016/j.annonc.2021.02.006

2. Study finds high tumor mutation burden predicts immunotherapy response in some, but not all, cancers. News release. University of Texas MD Anderson Cancer Center. Published March 15, 2021. Accessed March 30, 2021. https://www.mdanderson.org/newsroom/tumor-mutation-burden-predicts-immunotherapy-response-some-not-all-cancers.h00-159459267.html

https://www.cancernetwork.com/view/high-tumor-mutation-burden-predicts-response-to-immune-checkpoint-blockade-for-some-cancer-types

This site uses Akismet to reduce spam. Learn how your comment data is processed.