Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma

Abstract Development of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembroliz...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	S. C. Sasson, L. E. Wilkins, R. A. Watson, C. Jolly, O. Brain, P. Klenerman, A. Olsson-Brown, B. P. Fairfax
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb9be8f3099e4082999b755983e9f62a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bb9be8f3099e4082999b755983e9f62a
record_format	dspace
spelling	oai:doaj.org-article:bb9be8f3099e4082999b755983e9f62a2021-12-02T17:17:38ZIdentification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma10.1038/s41598-021-98700-72045-2322https://doaj.org/article/bb9be8f3099e4082999b755983e9f62a2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98700-7https://doaj.org/toc/2045-2322Abstract Development of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembrolizumab has not been well-studied. Enzyme-linked immunosorbent assays were used to measure pembrolizumab drug level and ADAs in 41 patients with melanoma at baseline, Time-point 1 (3 weeks) and Time-point 2 (21 weeks). Assay results were related to patient demographics and clinical outcome data at 6 months. The median pembrolizumab drug level at 3 weeks was 237 ng/μL and did not correlate with age, sex or body surface area.17/41 patients had an ADA detected at any timepoint, with the highest prevalence at Timepoint 1 (median concentration = 17 ng/μL). The presence of an ADA did not correlate with clinical progression at 6 months. 3/41 (7%) of patients displayed a falling pembrolizumab drug level and rising ADA titre between Timepoint 1 and 2 suggestive of a neutralising ADA. Pembrolizumab drug levels and ADAs can be readily measured. The rates of total and treatment-emergent ADAs may be higher in “real-word” settings than those previously reported. Larger studies are needed to determine effect of neutralising ADAs on long-term clinical outcome.S. C. SassonL. E. WilkinsR. A. WatsonC. JollyO. BrainP. KlenermanA. Olsson-BrownB. P. FairfaxNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-6 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. C. Sasson L. E. Wilkins R. A. Watson C. Jolly O. Brain P. Klenerman A. Olsson-Brown B. P. Fairfax Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
description	Abstract Development of anti-drug antibodies (ADAs) can interfere with therapeutic monoclonal antibodies and may lead to drug neutralisation and clinical disease progression. Measurement of circulating drug levels and development of ADAs in the setting of anti-programmed cell death-1 agent pembrolizumab has not been well-studied. Enzyme-linked immunosorbent assays were used to measure pembrolizumab drug level and ADAs in 41 patients with melanoma at baseline, Time-point 1 (3 weeks) and Time-point 2 (21 weeks). Assay results were related to patient demographics and clinical outcome data at 6 months. The median pembrolizumab drug level at 3 weeks was 237 ng/μL and did not correlate with age, sex or body surface area.17/41 patients had an ADA detected at any timepoint, with the highest prevalence at Timepoint 1 (median concentration = 17 ng/μL). The presence of an ADA did not correlate with clinical progression at 6 months. 3/41 (7%) of patients displayed a falling pembrolizumab drug level and rising ADA titre between Timepoint 1 and 2 suggestive of a neutralising ADA. Pembrolizumab drug levels and ADAs can be readily measured. The rates of total and treatment-emergent ADAs may be higher in “real-word” settings than those previously reported. Larger studies are needed to determine effect of neutralising ADAs on long-term clinical outcome.
format	article
author	S. C. Sasson L. E. Wilkins R. A. Watson C. Jolly O. Brain P. Klenerman A. Olsson-Brown B. P. Fairfax
author_facet	S. C. Sasson L. E. Wilkins R. A. Watson C. Jolly O. Brain P. Klenerman A. Olsson-Brown B. P. Fairfax
author_sort	S. C. Sasson
title	Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
title_short	Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
title_full	Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
title_fullStr	Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
title_full_unstemmed	Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
title_sort	identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bb9be8f3099e4082999b755983e9f62a
work_keys_str_mv	AT scsasson identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT lewilkins identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT rawatson identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT cjolly identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT obrain identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT pklenerman identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT aolssonbrown identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma AT bpfairfax identificationofneutralisingpembrolizumabantidrugantibodiesinpatientswithmelanoma
_version_	1718381165951320064

Identification of neutralising pembrolizumab anti-drug antibodies in patients with melanoma

Ejemplares similares