IRVING, Texas, May 11, 2026
Caris Life Sciences announced the publication of a new study in Cancer Immunology, Immunotherapy demonstrating that Whole Exome Sequencing (WES)-based tumor mutational burden (TMB) measurement provides significantly more accurate prediction of pembrolizumab immunotherapy benefit compared with TMB estimates generated from targeted gene panels. The large-scale real-world analysis showed that targeted gene panels incorrectly calculate TMB in approximately 10–15% of cancer patients, directly affecting eligibility decisions for pembrolizumab treatment. The findings reinforce growing clinical evidence supporting the use of ultra-deep WES as the most comprehensive genomic profiling method for precision oncology therapy selection. Caris stated that the study further validates the clinical value of its FDA-approved MI Cancer Seek assay, the first and only FDA-approved simultaneous Whole Exome Sequencing and Whole Transcriptome Sequencing-based companion diagnostic platform for molecular profiling of solid tumors.
Large Real-World Study Demonstrates Superiority of Whole Exome Sequencing
The study leveraged Caris Life Sciences’ large-scale clinico-genomic database containing 26,756 pembrolizumab-treated patients, making it one of the largest real-world immunotherapy biomarker analyses conducted to date. Researchers compared TMB scores measured directly through ultra-deep Whole Exome Sequencing with TMB estimates derived from commercially available targeted gene panels. Unlike targeted panels that analyze only selected portions of the genome, WES evaluates every protein-coding mutation capable of generating neoantigens associated with immune checkpoint inhibitor response. According to the study, discordance between WES-based TMB and panel-estimated TMB occurred in roughly 10–15% of cases, with higher error rates associated with smaller panel sizes.
Importantly, WES-based TMB demonstrated stronger correlation with overall survival outcomes among patients receiving pembrolizumab treatment. In discordant cases, patients classified as WES TMB-High but panel TMB-Low experienced significantly improved survival outcomes compared with patients categorized oppositely by targeted panels. Among a subset of “TMB-reliant” cancers lacking disease-specific immune checkpoint inhibitor indications, median overall survival was approximately five months longer in patients identified as TMB-High by WES compared with panel-based estimates.
Findings Could Influence Precision Oncology Testing Standards
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The publication adds significant weight to ongoing industry discussions regarding the optimal methodology for measuring tumor mutational burden in clinical oncology. TMB is widely used as a pan-tumor biomarker for determining eligibility for immune checkpoint inhibitors such as pembrolizumab, making accurate assessment critical for treatment decision-making. Caris executives emphasized that inaccurate TMB classification may expose patients either to ineffective immunotherapy or deny potentially beneficial treatment opportunities.
According to the company, Whole Exome Sequencing represents the current gold standard because it captures the full genomic landscape associated with neoantigen generation rather than relying on statistical estimations from limited gene subsets. The study also raises broader concerns regarding the reliability of smaller targeted sequencing panels increasingly used across commercial oncology diagnostics due to lower cost and faster turnaround times. Researchers concluded that WES-based TMB assessment more effectively identifies both responders and non-responders to pembrolizumab, particularly in tumor types where TMB serves as the primary biomarker guiding immunotherapy access.
Caris Expands AI-Driven Precision Oncology Platform
The findings further strengthen Caris Life Sciences’ position within the rapidly evolving AI-driven precision medicine and molecular diagnostics sector. The company continues expanding its integrated platform combining Whole Genome Sequencing, Whole Exome Sequencing, Whole Transcriptome Sequencing, artificial intelligence, and machine learning to support therapy selection, biomarker discovery, and drug development. In November 2024, Caris received FDA approval for MI Cancer Seek, a tissue-based assay capable of simultaneously performing WES and Whole Transcriptome Sequencing while providing quantitative TMB reporting with companion diagnostic indications for solid tumors.
Company leadership stated that the newly published data demonstrates the growing need for more comprehensive molecular profiling technologies as oncology increasingly shifts toward biomarker-guided treatment selection. Industry analysts believe studies like this may accelerate adoption of broader sequencing approaches in immuno-oncology as clinicians seek more reliable predictive biomarkers for checkpoint inhibitor therapies. With precision oncology becoming increasingly dependent on genomic interpretation and AI-supported analytics, Caris continues positioning itself at the intersection of next-generation sequencing and computational medicine.
Source: Caris Life Sciences press release
