Artículo
Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden
Autor/es | Morrison, Carl
Pabla, Sarabjot Conroy, Jeffrey M. Nesline, Mary K. Glenn, Sean T. Dressman, Devin Cruz Merino, Luis de la Ernstoff, Marc S. |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2018 |
Fecha de depósito | 2024-03-11 |
Publicado en |
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Resumen | 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 ... 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. |
Cita | Morrison, C., Pabla, S., Conroy, J.M., Nesline, M.K., Glenn, S.T., Dressman, D.,...,Ernstoff, M.S. (2018). Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden. Journal of Immunotherapy of Cancer, 6 (1), 32. https://doi.org/10.1186/s40425-018-0344-8. |
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