Landscape of tumor mutation burden and correlation to clinical outcomes in 1,744 solid cancers.

Authors

null

Jaeyun Jung

Samsung Medical Center, Seoul, South Korea

Jaeyun Jung , Sehhoon Park , Jeeyun Lee , Seung KIM

Organizations

Samsung Medical Center, Seoul, South Korea, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Research Funding

No funding received

Background: Tumor mutation burden (TMB) has proven clinical utility and efficacy related to immune checkpoint inhibitor (ICI) treatment in different tumor types. However, limited data were available to understand the landscape and matched clinical outcomes to a pan-cancer extent. Methods: Target sequencing results, using TruSight Oncology 500, from 1,744 solid cancer between 2019 and 2021 as a part of real-world clinical practice were collected. Matched clinical and histological outcomes, including PD-L1 expression (n= 798) and immunotherapy treatment (n= 400), were analyzed. Results: Among the 33 different cancer types, high TMB was observed in 257 patients (14.7%) with a significantly higher incidence observed in carcinoma of unknown origin (33.3%), bladder cancer (32.3%), and small bowel cancer (30.0%). TMB was positively correlated with the degree of mutation in homologous recombination genes (HRD, 0.76) and microsatellite instability (MSI, 0.51). The predictive value of high TMB to ICI treatment seemed to be enhanced when it was combined with PD-L1 expression, showing higher response rates in the PD-L1 high group (63.3%) than in the low group (22.2%). In the patients with high TMB, both longer overall survival (p = 0.015) and progression-free survival (p = 0.020) were observed compared to the patients with low TMB. Conclusions: We examined the landscape of TMB in a different type of cancer using clinical-level target sequencing outcomes. High TMB seems to be a promising predictive biomarker of ICI, showing a positive correlation with alteration in other DNA damage response and repair-related genes and additive value to PD-L1, which needs to be validated through further prospective trials.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics—Immunotherapy

Sub Track

Other IO-Related Topics

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 2667)

DOI

10.1200/JCO.2022.40.16_suppl.2667

Abstract #

2667

Poster Bd #

321

Abstract Disclosures