Dr. Hellmann on Tumor Mutational Burden in NSCLC

Matthew D. Hellmann, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the role tumor mutational burden (TMB) plays in determining combination therapies for patients with non—small cell lung cancer (NSCLC).

At first, people were uncertain whether or not TMD was truly identifying predictive markers. Emerging data has clarified that it is a predictive marker. Randomized studies of patients treated with PD-1 monotherapy or chemotherapy showed that only those patients who received PD-1 therapy had improvement based on TMD.

When researchers first looked at TMD as a biomarker they focused on patients treated with PD-1 monotherapy. There was uncertainty about whether or not the same sort of correlation would be seen in patients who received combination immunotherapy. Investigators wondered whether the additional immunotherapy might broaden the immune response that occurred and consequently diminish the importance of TMD.

However, the opposite is true in patients with both NSCLC and small cell lung cancer. TMD may matter even more in patients treated with combination immunotherapy. It has been a successful biomarker, particularly in patients treated with combination immunotherapy.