Evidence map›Paper›PMID 39240498›Full record

ArticleClinical pharmacokinetics2024

Investigating the Influence of Covariates on Axicabtagene Ciloleucel (axi-cel) Kinetics in Patients with Non-Hodgkin's Lymphoma.

Magali Chartier, Simone Filosto, Thomas Peyret, Manoj Chiney, Francesca Milletti, Justin Budka, Andre Ndi, Jinghui Dong, Saran Vardhanabhuti, Daqin Mao and 3 more

3 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

NCT02348216 phase1 / phase2completednot on this map

A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma

TypeinterventionalSponsorKite, A Gilead CompanyRan2015 to 2023Enrolled307ConditionsRefractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed Diffuse Large B-Cell Lymphoma, Transformed Follicular Lymphoma (TFL), Primary Mediastinal B-cell Lymphoma (PMBCL)ArmsAxicabtagene Ciloleucel, Fludarabine, Cyclophosphamide, Levetiracetam, Tocilizumab
NCT03105336 phase2completednot on this map

A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)

TypeinterventionalSponsorKite, A Gilead CompanyRan2017 to 2024Enrolled159ConditionsFollicular Lymphoma, Marginal Zone Lymphoma, Indolent Non-Hodgkin LymphomaArmsAxicabtagene ciloleucel, Cyclophosphamide, Fludarabine
NCT03391466 phase3completednot on this map

A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)

TypeinterventionalSponsorKite, A Gilead CompanyRan2018 to 2024Enrolled359ConditionsRelapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)ArmsAxicabtagene Ciloleucel, Platinum-containing Salvage Chemotherapy, Cyclophosphamide, Fludarabine
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. 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

13 authors.

Magali Chartier *Certara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA. magali.chartier@certara.com.ORCID 0000-0001-7659-8764
Simone Filosto *Kite, A Gilead Company, Santa Monica, CA, USA.
Thomas PeyretCertara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.
Manoj ChineyGilead Sciences, Parsipanny, NJ, USA.
Francesca MillettiKite, A Gilead Company, Santa Monica, CA, USA.
Justin BudkaKite, A Gilead Company, Santa Monica, CA, USA.
Andre NdiCertara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.
Jinghui DongKite, A Gilead Company, Santa Monica, CA, USA.
Saran VardhanabhutiKite, A Gilead Company, Santa Monica, CA, USA.
Daqin MaoKite, A Gilead Company, Santa Monica, CA, USA.
Stephen DuffullCertara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.
Michael DoddsCertara North America, Certara Canada, 2000 Peel Street, Suite 570 Montréal, Québec H3A 2W5, Radnor, PA, USA.
Rhine ShenKite, A Gilead Company, Santa Monica, CA, USA. rshen@kitepharma.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveAxicabtagene ciloleucel (axi-cel, Yescarta) is an autologous, anti-CD19, chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed and refractory non-Hodgkin's lymphoma. Substantial inter-individual variability in cellular kinetics has been observed with CAR-T therapies and factors impacting CAR-T cellular kinetics remain poorly understood. This work reports a population cellular kinetic model of axi-cel in relapsed and patients with refractory non-Hodgkin's lymphoma and investigated the impact of covariates on early and late kinetic phases of CAR-T exposure.

methodsA population cellular kinetic model (NONMEM

resultsAxi-cel cellular kinetics were well described by a piecewise model of cellular growth kinetics characterized by an exponential growth phase followed by a triphasic decline phase including a long-term persistence phase. The final cellular kinetic model retained in vitro doubling time during CAR-T cell manufacturing and total number of T cells infused as covariates impacting the duration of the growth phase, which, however, did not substantially influence maximum concentration, area under the concentration-time curve over the first 28 days, or long-term persistence. A statistically significant relationship was observed between maximum concentration and the probability to receive tocilizumab and/or corticosteroids.

conclusionsNo covariates considered in this study were found to significantly and substantially predict the exposure profile of axi-cel. Tocilizumab and steroid use were related to maximum concentration, but they were used reactively to treat toxicities that are associated with a higher maximum concentration. Further CAR-T kinetic analyses should consider additional factors to explain the observed variability in cellular kinetics or help establish a dose-exposure relationship. CLINICAL

trial registrationNCT02348216 (ZUMA-1), NCT03105336 (ZUMA-5), and NCT03391466 (ZUMA-7).

Indexed as

Antigens, CD19Biological ProductsImmunotherapy, AdoptiveLymphoma, Non-HodgkinAdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedModels, BiologicalReceptors, Chimeric AntigenYoung AdultAntigens, CD19axicabtagene ciloleucelBiological ProductsReceptors, Chimeric Antigen

Identifiers

PMID39240498

What OpenQuestion holds

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Registered trials

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.