Tumor Mutational Burden (TMB) Dichotomization for Immunotherapy Outcome Prediction

Lead Investigator: Li-Xuan Qin, Memorial Sloan Kettering Cancer Center
Title of Proposal Research: Tumor Mutational Burden (TMB) Dichotomization for Immunotherapy Outcome Prediction
Vivli Data Request: 9354
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Immunotherapy is a cancer treatment that harness the body’s immune system to attack cancer cells. With a response rate of about 15 to 20% across multiple cancer types, it can be a miraculous treatment for some patients, yet may not work for everyone. Moreover, it can result in negative outcomes in terms of expense, treatment related toxicity, and missed opportunities for other potentially effective treatments.

Tumor Mutational Burden (TMB) is a measure of genetic mutations, or changes in the DNA, present in a cancerous tumor. TMB has garnered considerable attention in the ongoing development of immunotherapy as a potential marker for patient response. The concept behind using TMB as a biomarker (which is measurable indicator of a biological process, condition, or disease state) for immunotherapy lies in the idea that tumors with more mutations may produce more abnormal proteins, known as neoantigens, which can be targeted by the immune system. Several clinical studies have indicated that patients with tumors exhibiting higher TMB levels tend to respond positively to immunotherapy. However, determining the appropriate cutoff value for defining a “high TMB” (that is, TMB dichotomization) remains a challenge. Conflicting evidence in the literature on the choice of the TMB cutoff has led to confusion in clinical practice.

Our research aims to address the critical issue of TMB dichotomization by analyzing data from multiple immunotherapy studies to identify a cutoff value that consistently predicts patient response. Through the aggregation of data from diverse studies and the application of advanced statistical methods for evaluating study replicability, we seek to establish a cutoff value that is both accurate and robust, ultimately leading to improved treatment outcomes for the approximately 1 in 5 people worldwide who develop cancer in their lifetime.

Requested Studies:

Assessment of Tumor Mutational Burden and Outcomes in Patients With Diverse Advanced Cancers Treated With Immunotherapy
Data Contributor: Tempus Labs, Inc.
Study ID: T23.01
Sponsor ID: T23.01