Evidence map›Paper›PMID 38877461›Full record

Observational studyBMC cancer2024

Monitoring immunE DysregulAtion foLLowing Immune checkpOint-inhibitioN (MEDALLION): protocol for an observational cancer immunotherapy cohort study.

Abigail Gault, Linda Hogarth, Kristian C Williams, Alastair Greystoke, Neil Rajan, Ally Speight, Christopher A Lamb, Alison Bridgewood, Lisa-Jayne Brown-Schofield, Fiona Rayner and 6 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
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

16 authors.

Abigail GaultTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Linda HogarthNorthern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Kristian C WilliamsTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Alastair GreystokeNorthern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Neil RajanTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Ally SpeightDepartment of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Christopher A LambTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Alison BridgewoodNorthern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Lisa-Jayne Brown-SchofieldNorthern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Fiona RaynerTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
John D IsaacsTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Jérémie NsengimanaPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Christopher J StewartTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Amy E AndersonTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Ruth PlummerTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK.
Arthur G PrattTranslational and Clinical Research Institute, The Medical School, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE4 2HH, UK. arthur.pratt@newcastle.ac.uk.

Funding

JGW Patterson Foundation 30015.088/9of19/PA/IXSVersus Arthritis 22072
6 · The paper itself

Abstract

backgroundCheckpoint inhibitors (CPIs) are widely used in cancer treatment, with transformative impacts on survival. They nonetheless carry a significant risk of toxicity in the form of immune-related adverse events (IrAEs), which may be sustained and life-altering. IrAEs may require high-dose and/or prolonged steroid use and represent a significant healthcare burden. They mimic immune-mediated inflammatory diseases (IMIDs) but understanding of their pathogenesis is limited. The MEDALLION project aims to determine targetable mechanisms of immune dysregulation in IrAE development, employing an immune monitoring approach to determine changes in circulating and tissue resident cells of CPI recipients who do/do not develop them and assessing the contribution of the microbiome in parallel.

methodsMEDALLION is a non-randomised longitudinal cohort study aiming to recruit 66 cancer patient recipients of anti-PD1/PD-L1, anti-CTLA-4 or combination therapy. Eligible participants include those with malignant melanoma in the adjuvant or metastatic setting, mesothelioma and non-small cell lung carcinoma (NSCLC) treated in the metastatic setting. Comprehensive clinical evaluation is carried out alongside blood, skin swab and stool sampling at the time of CPI initiation (baseline) and during subsequent routine hospital visits on 6 occasions over a 10-month follow-up period. It is conservatively anticipated that one third of enrolled patients will experience a "significant IrAE" (SirAE), defined according to pre-determined criteria specific to the affected tissue/organ system. Those developing such toxicity may optionally undergo a biopsy of affected tissue where appropriate, otherwise being managed according to standard of care. Peripheral blood mononuclear cells will be analysed using multi-parameter flow cytometry to investigate immune subsets, their activation status and cytokine profiles. Stool samples and skin swabs will undergo DNA extraction for 16 S ribosomal RNA (rRNA) sequencing and internal transcribed spacer (ITS) gene sequencing to determine bacterial and fungal microbiome diversity, respectively, including species associated with toxicity. Stored tissue biopsies will be available for in situ and single-cell transcriptomic evaluation. Analysis will focus on the identification of biological predictors and precursors of SirAEs. DISCUSSION: The pathogenesis of IrAEs will be assessed through the MEDALLION cohort, with the potential to develop tools for their prediction and/or strategies for targeted prevention or treatment.

trial registrationThe study was registered on 18/09/2023 in the ISRCTN registry (43,419,676).

Indexed as

Immune Checkpoint InhibitorsNeoplasmsCohort StudiesHumansImmunotherapyLongitudinal StudiesMelanomaMonitoring, ImmunologicImmune Checkpoint InhibitorsCancerCheckpoint inhibitorCohort studyImmune related adverse eventsImmunotherapyPathogenesis

Identifiers

PMID38877461
PMCPMC11179333

What OpenQuestion holds

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Registered trials

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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.