Evidence map›Paper›PMID 34584157›Full record

Observational studyScientific reports2021

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

S C Sasson, L E Wilkins, R A Watson, C Jolly, O Brain, P Klenerman, A Olsson-Brown, B P Fairfax

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Dostarlimab: A Review.Biomolecules · 2022
    Review
  7. Review
  8. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

S C Sasson *Nuffield Department of Medicine, The University of Oxford, Oxford, UK. sarah.sasson@ndm.ox.ac.uk.
L E Wilkins *The University of Oxford Medical School, Oxford, UK.
R A WatsonMRC Weatherall Institute of Molecular Medicine, The University of Oxford, Oxford, UK.
C JollyThe Clatterbridge Cancer Centre, Liverpool, UK.
O BrainNuffield Department of Medicine, The University of Oxford, Oxford, UK.
P KlenermanNuffield Department of Medicine, The University of Oxford, Oxford, UK.
A Olsson-BrownThe Clatterbridge Cancer Centre, Liverpool, UK.
B P FairfaxMRC Weatherall Institute of Molecular Medicine, The University of Oxford, Oxford, UK.
University of Oxford · GBClatterbridge Cancer Centre NHS Foundation Trust · GBMRC Weatherall Institute of Molecular Medicine · GB

Funding

Wellcome Trust 201488/Z/16/Z
6 · The paper itself

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.

Indexed as

AgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntineoplastic Agents, ImmunologicalDisease ProgressionDrug MonitoringFemaleHumansMaleMelanomaSkin NeoplasmsTreatment OutcomeAntibodies, Monoclonal, HumanizedAntibodies, NeutralizingAntineoplastic Agents, Immunologicalpembrolizumab

Identifiers

PMID34584157
PMCPMC8478874
OpenAlexW3202978616

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.