| Autor: |
Amin H. Nassar, Elio Adib, Sarah Abou Alaiwi, Talal El Zarif, Stefan Groha, Elie W. Akl, Pier Vitale Nuzzo, Tarek H. Mouhieddine, Tomin Perea-Chamblee, Kodi Taraszka, Habib El-Khoury, Muhieddine Labban, Christopher Fong, Kanika S. Arora, Chris Labaki, Wenxin Xu, Guru Sonpavde, Robert I. Haddad, Kent W. Mouw, Marios Giannakis, F. Stephen Hodi, Noah Zaitlen, Adam J. Schoenfeld, Nikolaus Schultz, Michael F. Berger, Laura E. MacConaill, Guruprasad Ananda, David J. Kwiatkowski, Toni K. Choueiri, Deborah Schrag, Jian Carrot-Zhang, Alexander Gusev |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Cancer Cell. 40:1161-1172.e5 |
| ISSN: |
1535-6108 |
| DOI: |
10.1016/j.ccell.2022.08.022 |
| Popis: |
The immune checkpoint inhibitor (ICI) pembrolizumab is US FDA approved for treatment of solid tumors with high tumor mutational burden (TMB-high; ≥10 variants/Mb). However, the extent to which TMB-high generalizes as an accurate biomarker in diverse patient populations is largely unknown. Using two clinical cohorts, we investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing in solid tumors. TMB estimates from tumor-only panels substantially overclassified individuals into the clinically important TMB-high group due to germline contamination, and this bias was particularly pronounced in patients with Asian/African ancestry. Among patients with non-small cell lung cancer treated with ICIs, those misclassified as TMB-high from tumor-only panels did not associate with improved outcomes. TMB-high was significantly associated with improved outcomes only in European ancestries and merits validation in non-European ancestry populations. Ancestry-aware tumor-only TMB calibration and ancestry-diverse biomarker studies are critical to ensure that existing disparities are not exacerbated in precision medicine. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
