RT Journal Article
T1 Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden.
A1 Morrison, Carl
A1 Pabla, Sarabjot
A1 Conroy, Jeffrey M
A1 Nesline, Mary K
A1 Glenn, Sean T
A1 Dressman, Devin
A1 Papanicolau-Sengos, Antonios
A1 Burgher, Blake
A1 Andreas, Jonathan
A1 Giamo, Vincent
A1 Qin, Moachun
A1 Wang, Yirong
A1 Lenzo, Felicia L
A1 Omilian, Angela
A1 Bshara, Wiam
A1 Zibelman, Matthew
A1 Ghatalia, Pooja
A1 Dragnev, Konstantin
A1 Shirai, Keisuke
A1 Madden, Katherine G
A1 Tafe, Laura J
A1 Shah, Neel
A1 Kasuganti, Deepa
A1 de la Cruz-Merino, Luis
A1 Araujo, Isabel
A1 Saenger, Yvonne
A1 Bogardus, Margaret
A1 Villalona-Calero, Miguel
A1 Diaz, Zuanel
A1 Day, Roger
A1 Eisenberg, Marcia
A1 Anderson, Steven M
A1 Puzanov, Igor
A1 Galluzzi, Lorenzo
A1 Gardner, Mark
A1 Ernstoff, Marc S
K1 Algorithmic analysis
K1 Borderline
K1 Immune Desert
K1 Inflamed
K1 Ipilimumab
K1 Nivolumab
K1 Pembrolizumab
AB Immune checkpoint inhibitors (ICIs) have changed the clinical management of melanoma. However, not all patients respond, and current biomarkers including PD-L1 and mutational burden show incomplete predictive performance. The clinical validity and utility of complex biomarkers have not been studied in melanoma. Cutaneous metastatic melanoma patients at eight institutions were evaluated for PD-L1 expression, CD8+ T-cell infiltration pattern, mutational burden, and 394 immune transcript expression. PD-L1 IHC and mutational burden were assessed for association with overall survival (OS) in 94 patients treated prior to ICI approval by the FDA (historical-controls), and in 137 patients treated with ICIs. Unsupervised analysis revealed distinct immune-clusters with separate response rates. This comprehensive immune profiling data were then integrated to generate a continuous Response Score (RS) based upon response criteria (RECIST v.1.1). RS was developed using a single institution training cohort (n = 48) and subsequently tested in a separate eight institution validation cohort (n = 29) to mimic a real-world clinical scenario. PD-L1 positivity ≥1% correlated with response and OS in ICI-treated patients, but demonstrated limited predictive performance. High mutational burden was associated with response in ICI-treated patients, but not with OS. Comprehensive immune profiling using RS demonstrated higher sensitivity (72.2%) compared to PD-L1 IHC (34.25%) and tumor mutational burden (32.5%), but with similar specificity. In this study, the response score derived from comprehensive immune profiling in a limited melanoma cohort showed improved predictive performance as compared to PD-L1 IHC and tumor mutational burden.
YR 2018
FD 2018-05-09
LK http://hdl.handle.net/10668/12439
UL http://hdl.handle.net/10668/12439
LA en
DS RISalud
RD Apr 6, 2025