Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study.


Journal

Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R

Informations de publication

Date de publication:
19 09 2020
Historique:
received: 06 05 2020
revised: 22 05 2020
accepted: 09 06 2020
pubmed: 6 9 2020
medline: 21 10 2020
entrez: 5 9 2020
Statut: ppublish

Résumé

Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas. We did a seamless design study at 14 cancer centres in the USA. We enrolled adult patients (aged ≥18 years) with relapsed or refractory large B-cell lymphomas. Eligible histological subgroups included diffuse large B-cell lymphoma, high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), diffuse large B-cell lymphoma transformed from any indolent lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B. Patients were assigned to one of three target dose levels of liso-cel as they were sequentially tested in the trial (50 × 10 Between Jan 11, 2016, and July 5, 2019, 344 patients underwent leukapheresis for manufacture of CAR Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies. Juno Therapeutics, a Bristol-Myers Squibb Company.

Sections du résumé

BACKGROUND
Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product. We aimed to assess the activity and safety of liso-cel in patients with relapsed or refractory large B-cell lymphomas.
METHODS
We did a seamless design study at 14 cancer centres in the USA. We enrolled adult patients (aged ≥18 years) with relapsed or refractory large B-cell lymphomas. Eligible histological subgroups included diffuse large B-cell lymphoma, high-grade B-cell lymphoma with rearrangements of MYC and either BCL2, BCL6, or both (double-hit or triple-hit lymphoma), diffuse large B-cell lymphoma transformed from any indolent lymphoma, primary mediastinal B-cell lymphoma, and follicular lymphoma grade 3B. Patients were assigned to one of three target dose levels of liso-cel as they were sequentially tested in the trial (50 × 10
FINDINGS
Between Jan 11, 2016, and July 5, 2019, 344 patients underwent leukapheresis for manufacture of CAR
INTERPRETATION
Use of liso-cel resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory large B-cell lymphomas, including those with diverse histological subtypes and high-risk features. Liso-cel is under further evaluation at first relapse in large B-cell lymphomas and as a treatment for other relapsed or refractory B-cell malignancies.
FUNDING
Juno Therapeutics, a Bristol-Myers Squibb Company.

Identifiants

pubmed: 32888407
pii: S0140-6736(20)31366-0
doi: 10.1016/S0140-6736(20)31366-0
pii:
doi:

Substances chimiques

Antigens, CD19 0
Biological Products 0
axicabtagene ciloleucel U2I8T43Y7R

Banques de données

ClinicalTrials.gov
['NCT02631044']

Types de publication

Clinical Trial Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

839-852

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Jeremy S Abramson (JS)

Massachusetts General Hospital Cancer Center, Boston, MA, USA. Electronic address: jabramson@mgh.harvard.edu.

M Lia Palomba (ML)

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Leo I Gordon (LI)

Northwestern University Feinberg School of Medicine, Robert H Lurie Comprehensive Cancer Center, Chicago, IL, USA.

Matthew A Lunning (MA)

University of Nebraska Medical Center, Omaha, NE, USA.

Michael Wang (M)

University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jon Arnason (J)

Beth Israel Deaconess Medical Center, Boston, MA, USA.

Amitkumar Mehta (A)

University of Alabama at Birmingham, Birmingham, AL, USA.

Enkhtsetseg Purev (E)

University of Colorado School of Medicine, Aurora, CO, USA.

David G Maloney (DG)

Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Charalambos Andreadis (C)

University of California, San Francisco, San Francisco, CA, USA.

Alison Sehgal (A)

University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA.

Scott R Solomon (SR)

Northside Hospital Cancer Institute, Atlanta, GA, USA.

Nilanjan Ghosh (N)

Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.

Tina M Albertson (TM)

Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA, USA.

Jacob Garcia (J)

Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA, USA.

Ana Kostic (A)

Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA, USA.

Mary Mallaney (M)

Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA, USA.

Ken Ogasawara (K)

Bristol-Myers Squibb, Princeton, NJ, USA.

Kathryn Newhall (K)

Bristol-Myers Squibb, Seattle, WA, USA.

Yeonhee Kim (Y)

Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA, USA.

Daniel Li (D)

Juno Therapeutics, a Bristol-Myers Squibb Company, Seattle, WA, USA.

Tanya Siddiqi (T)

City of Hope National Medical Center, Duarte, CA, USA.

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Classifications MeSH