Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden.

Autor: Morrison C; Center for Personalized Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA. Carl.Morrison@RoswellPark.org.; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA. Carl.Morrison@RoswellPark.org.; Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA. Carl.Morrison@RoswellPark.org.; OmniSeq Inc., Buffalo, NY, 14203, USA. Carl.Morrison@RoswellPark.org., Pabla S; OmniSeq Inc., Buffalo, NY, 14203, USA., Conroy JM; Center for Personalized Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.; OmniSeq Inc., Buffalo, NY, 14203, USA., Nesline MK; OmniSeq Inc., Buffalo, NY, 14203, USA., Glenn ST; Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.; OmniSeq Inc., Buffalo, NY, 14203, USA., Dressman D; OmniSeq Inc., Buffalo, NY, 14203, USA., Papanicolau-Sengos A; OmniSeq Inc., Buffalo, NY, 14203, USA., Burgher B; OmniSeq Inc., Buffalo, NY, 14203, USA., Andreas J; OmniSeq Inc., Buffalo, NY, 14203, USA., Giamo V; OmniSeq Inc., Buffalo, NY, 14203, USA., Qin M; OmniSeq Inc., Buffalo, NY, 14203, USA., Wang Y; OmniSeq Inc., Buffalo, NY, 14203, USA., Lenzo FL; OmniSeq Inc., Buffalo, NY, 14203, USA., Omilian A; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA., Bshara W; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA., Zibelman M; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA., Ghatalia P; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA., Dragnev K; Department of Hematology and Oncology, Dartmouth Hitchcock, Lebanon, NH, 03756, USA., Shirai K; Department of Hematology and Oncology, Dartmouth Hitchcock, Lebanon, NH, 03756, USA., Madden KG; Department of Hematology and Oncology, Dartmouth Hitchcock, Lebanon, NH, 03756, USA., Tafe LJ; Department of Hematology and Oncology, Dartmouth Hitchcock, Lebanon, NH, 03756, USA.; Department of Pathology, Dartmouth Hitchcock, Lebanon, NH, 03756, USA., Shah N; Department of Pathology, Community Hospital, Munster, IN, 46321, USA., Kasuganti D; Department of Pathology, Community Hospital, Munster, IN, 46321, USA., de la Cruz-Merino L; Department of Clinical Oncology Development, Hospital Universitario Virgen Macarena, 41009, Sevilla, Spain., Araujo I; Department of Clinical Oncology Development, Hospital Universitario Virgen Macarena, 41009, Sevilla, Spain., Saenger Y; Department of Medicine, Columbia University, New York, NY, 10032, USA., Bogardus M; Department of Medicine, Columbia University, New York, NY, 10032, USA., Villalona-Calero M; Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA., Diaz Z; Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA., Day R; Department of Biomedical Informatics and Biostatistics, University of Pittsburgh, Pittsburgh, PA, 15213, USA., Eisenberg M; Laboratory Corporation of America Holdings, Burlington, NC, 27215, USA., Anderson SM; Laboratory Corporation of America Holdings, Burlington, NC, 27215, USA., Puzanov I; Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA., Galluzzi L; Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, 10065, USA.; Sandra and Edward Meyer Cancer Center, New York, NY, 10065, USA.; Université Paris Descartes/Paris V, 75006, Paris, France., Gardner M; OmniSeq Inc., Buffalo, NY, 14203, USA., Ernstoff MS; Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263, USA.
Jazyk: angličtina
Zdroj: Journal for immunotherapy of cancer [J Immunother Cancer] 2018 May 09; Vol. 6 (1), pp. 32. Date of Electronic Publication: 2018 May 09.
DOI: 10.1186/s40425-018-0344-8
Abstrakt: 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.
Databáze: MEDLINE
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