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Tumor Mutational Burden: A Key Player in Immune Checkpoint Inhibitor Therapy Outcomes

This article discusses a study on the relationship between tumor mutational burden and outcomes in patients with advanced cancers treated with immune checkpoint inhibitors.

In the realm of advanced cancer treatment, the role of tumor mutational burden (TMB) and immune checkpoint inhibitors is gaining significant attention. A recent study led by Dr. Charu Aggarwal, published in JAMA Network Open, sheds light on this crucial relationship.


Understanding Tumor Mutational Burden

Tumor Mutational Burden (TMB) is a measure of the number of mutations within a tumor. The study found that patients with advanced solid cancers and a high tumor mutational burden (TMB-H) had improved overall survival when treated with immune checkpoint inhibitor therapy compared to those with a low tumor mutational burden (TMB-L).


The Study Details

The study analyzed data from patients in the Tempus database, which includes 199 community sites and 101 academic sites. The patients had undergone next-generation sequencing (Tempus xT) between 2018 and 2022. The study focused on patients with advanced solid tumors across eight cancer types who were treated with FDA-approved immune checkpoint inhibitors in the first- or second-line setting. The primary outcome measure was the association of TMB-H (≥ 10 mut/mb) vs TMB-L with overall survival.


Key Findings

The total evaluable cohort consisted of 674 patients, with a mean age of 69.4 years. The most common cancers in the cohort were non-small cell lung cancer (NSCLC, 49.0%), bladder cancer (22.0%), and head and neck squamous cell carcinoma (14.8%). A total of 206 patients (30.6%) had TMB-H cancers.

The study found that median overall survival was significantly better in the TMB-H group vs the TMB-L group. This finding was consistent across different types of immune checkpoint inhibitors, including pembrolizumab and others, and in analysis adjusting for PD-L1 expression and microsatellite stability status.


Conclusion

The study concluded that in patients with advanced solid tumors treated with immune checkpoint inhibitors, TMB-H cancers were significantly associated with improved clinical outcomes compared to TMB-L cancers. This finding underscores the importance of considering tumor mutational burden in the treatment of advanced cancers with immune checkpoint inhibitors.


Repost From Original Article: The ASCO Post

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