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Morrison C , Pabla S , Conroy JM , Nesline MK , Glenn ST , Dressman D , Papanicolau-Sengos A , Burgher B , Andreas J , Giamo V , Qin M , Wang Y , Lenzo FL , Omilian A , Bshara W , Zibelman M , Ghatalia P , Dragnev K , Shirai K , Madden KG , Tafe LJ , Shah N , Kasuganti D , de la Cruz-Merino L , Araujo I , Saenger Y , Bogardus M , Villalona-Calero M , Diaz Z , Day R , Eisenberg M , Anderson SM , Puzanov I , Galluzzi L , Gardner M , Ernstoff MS
Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden
J Immunother Cancer. 2018 May 9;6(1) :32
PMID: 29743104    PMCID: PMC5944039   
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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
2051-1426 Morrison, Carl ORCID: http://orcid.org/0000-0002-3441-8363 Pabla, Sarabjot Conroy, Jeffrey M Nesline, Mary K Glenn, Sean T Dressman, Devin Papanicolau-Sengos, Antonios Burgher, Blake Andreas, Jonathan Giamo, Vincent Qin, Moachun Wang, Yirong Lenzo, Felicia L Omilian, Angela Bshara, Wiam Zibelman, Matthew Ghatalia, Pooja Dragnev, Konstantin Shirai, Keisuke Madden, Katherine G Tafe, Laura J Shah, Neel Kasuganti, Deepa de la Cruz-Merino, Luis Araujo, Isabel Saenger, Yvonne Bogardus, Margaret Villalona-Calero, Miguel Diaz, Zuanel Day, Roger Eisenberg, Marcia Anderson, Steven M Puzanov, Igor Galluzzi, Lorenzo Gardner, Mark Ernstoff, Marc S Journal Article England J Immunother Cancer. 2018 May 9;6(1):32. doi: 10.1186/s40425-018-0344-8.