Evidence map›Paper›PMID 31012549›Full record

ArticlePediatric blood & cancer2019

Preclinical activity of the antibody-drug conjugate denintuzumab mafodotin (SGN-CD19A) against pediatric acute lymphoblastic leukemia xenografts.

Luke Jones, Hannah McCalmont, Kathryn Evans, Chelsea Mayoh, Raushan T Kurmasheva, Catherine A Billups, Peter J Houghton, Malcolm A Smith, Richard B Lock

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric blood & cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.3field-weighted citation impact, top 8% 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, 28 citations in OpenAlex.

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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

9 authors at 4 institutions in 2 countries.

Luke JonesChildren's Cancer Institute, School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.
Hannah McCalmontChildren's Cancer Institute, School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.
Kathryn EvansChildren's Cancer Institute, School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.
Chelsea MayohChildren's Cancer Institute, School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.
Raushan T KurmashevaGreehey Children's Cancer Research Institute, University of Texas Health Science Center San Antonio, San Antonio, Texas.ORCID 0000-0003-3212-2363
Catherine A BillupsSt. Jude Children's Research Hospital, Memphis, Tennessee.
Peter J HoughtonGreehey Children's Cancer Research Institute, University of Texas Health Science Center San Antonio, San Antonio, Texas.
Malcolm A SmithCancer Therapy Evaluation Program, NCI, Bethesda, Maryland.
Richard B LockChildren's Cancer Institute, School of Women's and Children's Health, UNSW Sydney, Sydney, New South Wales, Australia.
UNSW Sydney · AUThe University of Texas Health Science Center at San Antonio · USCenter for Cancer Research · USSt. Jude Children's Research Hospital · US

Funding

Pediatric Preclinical Testing Consortium - LeukemiaU01CA199000 · NCI · UNIVERSITY OF NEW SOUTH WALES · PI Richard B Lock · 2015 to 2026
$4.8M
Pediatric Preclinical Testing Consortium: Research Programs Non-CNS (U01)U01CA199297 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI HOUGHTON, PETER J · 2015 to 2021
$3.5M
A Testing Program to Identify Novel Agents for Treatment of Pediatric and AYA High-Risk Sarcoma, Kidney and Liver CancerU01CA263981 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Raushan Kurmasheva · 2021 to 2026
$3.2M
ANTINEOPLASTIC ALKYLGLYCEROLIPIDSR01CA042216 · NCI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI PIANTADOSI, CLAUDE · 1988 to 1990
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NCI NIH HHS N01 CM042216NCI NIH HHS NOI-CM-42216NCI NIH HHS NOI-CM-91001-03,NCI NIH HHS U01 CA199000NCI NIH HHS U01-CA199000NCI NIH HHS U01 CA199297NCI NIH HHS U01 CA263981
6 · The paper itself

Abstract

backgroundDenintuzumab mafodotin (SGN-CD19A) is a CD19-targeting antibody-drug conjugate, comprising a monoclonal antibody conjugated to the potent cytotoxin monomethyl auristatin F. Since denintuzumab mafodotin has previously shown activity against B-cell malignancies in early-stage clinical trials, it was of interest to test it against the Pediatric Preclinical Testing Program preclinical models of CD19 PROCEDURES: Denintuzumab mafodotin was evaluated against eight B-cell lineage ALL patient-derived xenografts (PDXs), representing B-cell precursor ALL, Ph-like ALL, and mixed-lineage leukemia rearranged infant ALL. Denintuzumab mafodotin was administered weekly for 3 weeks at 3 mg/kg. It was also tested in combination with an induction-type chemotherapy regimen of vincristine, dexamethasone, and l-asparaginase (VXL) against three PDXs. The relationship between cell surface and gene expression of CD19 and drug activity was also assessed.

resultsDenintuzumab mafodotin significantly delayed the progression of seven of eight PDXs tested and achieved objective responses in five of eight. There was no apparent subtype specificity of denintuzumab mafodotin activity. No correlations were observed between CD19 mRNA or cell surface expression and denintuzumab mafodotin activity, perhaps due to small sample size, and denintuzumab mafodotin treatment did not select for reduced CD19 expression. Combining denintuzumab mafodotin with VXL achieved therapeutic enhancement compared to either treatment alone.

conclusionsDenintuzumab mafodotin showed single-agent activity against selected B-lineage ALL PDXs, although leukemia growth was evident in most models at 28 days from treatment initiation. This level of activity for denintuzumab mafodotin is consistent with that observed in adults with ALL.

Indexed as

AdolescentAnimalsAntibodies, Monoclonal, HumanizedAntigens, CD19ChildChild, PreschoolDrug Evaluation, PreclinicalFemaleHumansImmunoconjugatesInfantInfant, NewbornMaleMice, Inbred NODMice, SCIDOligopeptidesAntibodies, Monoclonal, HumanizedAntigens, CD19Immunoconjugatesmonomethylauristatin FOligopeptidesCD19leukemiapatient-derived xenograftpediatric oncology

Identifiers

PMID31012549
PMCPMC6588422
OpenAlexW2942141310

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.