dc.creator | Morrison, Carl | es |
dc.creator | Pabla, Sarabjot | es |
dc.creator | Conroy, Jeffrey M. | es |
dc.creator | Nesline, Mary K. | es |
dc.creator | Glenn, Sean T. | es |
dc.creator | Dressman, Devin | es |
dc.creator | Cruz Merino, Luis de la | es |
dc.creator | Ernstoff, Marc S. | es |
dc.date.accessioned | 2024-03-11T19:01:28Z | |
dc.date.available | 2024-03-11T19:01:28Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | 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. | |
dc.identifier.issn | 2051-1426 | es |
dc.identifier.uri | https://hdl.handle.net/11441/156114 | |
dc.description.abstract | 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. | es |
dc.format | application/pdf | es |
dc.format.extent | 12 p. | es |
dc.language.iso | eng | es |
dc.publisher | BMC | es |
dc.relation.ispartof | Journal of Immunotherapy of Cancer, 6 (1), 32. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Pembrolizumab | es |
dc.subject | Nivolumab | es |
dc.subject | Ipilimumab | es |
dc.subject | Algorithmic analysis | es |
dc.subject | Inflamed | es |
dc.subject | Borderline | es |
dc.subject | Immune Desert | es |
dc.title | Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden | es |
dc.type | info:eu-repo/semantics/article | es |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://jitc.bmj.com/content/6/1/32 | es |
dc.identifier.doi | 10.1186/s40425-018-0344-8 | es |
dc.contributor.group | Universidad de Sevilla. CTS151: Bioquímica médica. | es |
dc.journaltitle | Journal of Immunotherapy of Cancer | es |
dc.publication.volumen | 6 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 32 | es |