Evidence map›Paper›PMID 34076364›Full record

ArticleCPT: pharmacometrics & systems pharmacology2021

Population pharmacokinetics of belantamab mafodotin, a BCMA-targeting agent in patients with relapsed/refractory multiple myeloma.

Chetan Rathi, Jon Collins, Herbert Struemper, Joanna Opalinska, Roxanne C Jewell, Geraldine Ferron-Brady

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

Article in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 27 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

6 authors at 1 institution in 1 country.

Chetan RathiGlaxoSmithKline, Collegeville, Pennsylvania, USA.
Jon CollinsGlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Herbert StruemperGlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Joanna OpalinskaGlaxoSmithKline, Collegeville, Pennsylvania, USA.
Roxanne C JewellGlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Geraldine Ferron-BradyGlaxoSmithKline, Collegeville, Pennsylvania, USA.
GlaxoSmithKline (United States) · US

Funding

GlaxoSmithKline 117159GlaxoSmithKline 205678
6 · The paper itself

Abstract

Belantamab mafodotin (belamaf) is an antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA). Nonlinear mixed-effects models were developed to characterize the population pharmacokinetics (PopPK) of ADC, total monoclonal antibody (mAb), and cysteine-maleimidocaproyl-MMAF (cys-mcMMAF) after 0.03-4.6 mg/kg dosing every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM; DREAMM-1, n = 73; DREAMM-2, n = 218). Sequential modeling methodology was used. Individual post hoc parameter estimates from the final ADC model were used to develop total mAb and cys-mcMMAF models. Formal covariate selection used a modified stepwise forward inclusion method with backward elimination. A linear, two-compartment PopPK model with a time-varying clearance (CL) described ADC PK. Initial ADC typical value for CL for a DREAMM-2 patient was 0.936 L/day with a half-life of 11.5 days, over time CL was reduced by 28% resulting in a half-life of 14.3 days. Time to 50% maximal CL change was ~ 50 days. Baseline soluble BCMA (sBCMA), immunoglobulin (IgG), albumin, and bodyweight impacted ADC CL. Cys-mcMMAF concentrations were described with a linear two-compartment model linked to ADC; input rate was governed by deconjugation/intracellular proteolytic degradation of ADC represented by an exponentially decreasing MMAF:mAb (drug antibody ratio [DAR]) after each dose. Time to 50% DAR reduction was 10.3 days. Baseline sBCMA and IgG impacted cys-mcMMAF central volume of distribution. In conclusion, ADC, total mAb, and cys-mcMMAF concentration-time profiles in RRMM were well-described by PopPK models, and exposure was most strongly impacted by disease-related characteristics.

Indexed as

Models, BiologicalAgedAntibodies, Monoclonal, HumanizedB-Cell Maturation AntigenDose-Response Relationship, DrugFemaleHumansLinear ModelsMaleMultiple MyelomaNonlinear DynamicsRandomized Controlled Trials as TopicTissue DistributionAntibodies, Monoclonal, HumanizedB-Cell Maturation Antigenbelantamab mafodotin

Identifiers

PMID34076364
PMCPMC8376139
OpenAlexW3164873993

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.