Targeted gene panels miscalculate tumor mutational burden in 10–15% of patients, directly resulting in incorrect pembrolizumab eligibility determination

IRVING, Texas, May 11, 2026 /PRNewswire/ — Caris Life Sciences^® (NASDAQ: CAI), a leading, patient-centric, next-generation AI TechBio company and precision medicine pioneer, has published a study in Cancer Immunology, Immunotherapy demonstrating that measuring tumor mutational burden (TMB) using ultra-deep Whole Exome Sequencing (WES) provides superior prediction of pembrolizumab immunotherapy benefit compared to estimates of TMB from targeted gene panels. TMB is a pan-tumor biomarker used to determine patients’ eligibility for pembrolizumab. These findings highlight the importance of testing all cancer patients with ultra-deep WES, the only truly comprehensive genomic profile for therapy selection.

The study used Caris’ large-scale, real-world clinico-genomic database, containing 26,756 patients treated with pembrolizumab who were evaluable for this study. WES provides a true measurement of TMB by interrogating every protein-coding gene mutation that may create a neoantigen, in comparison to targeted panels that only estimate TMB with incomplete gene coverage.

Key findings include:

• The analysis compared WES-measured TMB with commercially available targeted panel estimates of TMB and found discordance in 10-15% of cases, with error rates correlating to panel size.
• In discordant cases, WES TMB more accurately predicted overall survival in pembrolizumab-treated patients than panel-based estimates.
• In a subset of ‘TMB reliant’ patients (n = 3,981), for example, patients with tumor types that lack disease-specific immune checkpoint inhibitor indications, the median overall survival in discordant cases was about five months longer for WES TMB-High and panel TMB-Low compared to WES TMB-Low and panel TMB-High cases treated with pembrolizumab.

“These findings underscore the critical importance of using Whole Exome Sequencing to guide immunotherapy decisions,” said Milan Radovich, PhD, Senior Vice President, Chief Scientific Officer at Caris. “Whole Exome Sequencing is the gold-standard for determination of tumor mutational burden, ensuring that patients who stand to benefit from pembrolizumab are correctly identified and that those unlikely to respond are not exposed to unnecessary treatment.”

The study concludes that WES-based TMB measurements are a superior predictor of pembrolizumab benefit than panel-based TMB estimates and more reliably identify both patients who may benefit from therapy and those unlikely to respond, particularly in tumor types where TMB is the primary biomarker guiding access to immune checkpoint inhibitors.

Caris received FDA approval in November 2024 for MI Cancer Seek. This tissue-based assay is the first and only simultaneous WES and Whole Transcriptome Sequencing (WTS)-based assay with FDA-approved companion diagnostic (CDx) indications for molecular profiling of solid tumors and includes quantitative reporting of TMB.

About Caris Life Sciences
Caris Life Sciences^® (Caris) is a leading, patient-centric, next-generation AI TechBio company and precision medicine pioneer actively developing and commercializing innovative solutions to transform healthcare. Through comprehensive molecular profiling (Whole Genome, Whole Exome and Whole Transcriptome Sequencing), advanced AI and machine learning, Caris has created the large-scale, multimodal clinico-genomic database and computing capability needed to analyze and further unravel the molecular complexity of disease. This convergence of next-generation sequencing, AI and machine learning technologies and high-performance computing provides a differentiated platform for developing the latest generation of advanced precision medicine diagnostic solutions for early detection, diagnosis, monitoring, therapy selection and drug development.  

Caris was founded with a vision to realize the potential of precision medicine to improve the human condition. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Cambridge (MA), Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S. and other international markets.  

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