PMID- 35314842
OWN - NLM
STAT- MEDLINE
DCOM- 20220421
LR  - 20240229
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 28
IP  - 4
DP  - 2022 Apr
TI  - Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: 
      the phase 2 ZUMA-12 trial.
PG  - 735-742
LID - 10.1038/s41591-022-01731-4 [doi]
AB  - High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line 
      chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study 
      (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), 
      an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part 
      of first-line treatment in 40 patients with high-risk LBCL. This trial has 
      completed accrual. The primary outcome was complete response rate (CRR). 
      Secondary outcomes were objective response rate (ORR), duration of response 
      (DOR), event-free survival (EFS), progression-free survival (PFS), overall 
      survival (OS), assessment of safety, central nervous system (CNS) relapse and 
      blood levels of CAR T cells and cytokines. The primary endpoint in 
      efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence 
      interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median 
      follow-up, 15.9 months), 73% of patients remained in objective response; median 
      DOR, EFS and PFS were not reached. Grade >/=3 cytokine release syndrome (CRS) and 
      neurologic events occurred in three patients (8%) and nine patients (23%), 
      respectively. There were no treatment-related grade 5 events. Robust CAR T-cell 
      expansion occurred in all patients with a median time to peak of 8 days. We 
      conclude that axi-cel is highly effective as part of first-line therapy for 
      high-risk LBCL, with a manageable safety profile.
CI  - (c) 2022. The Author(s).
FAU - Neelapu, Sattva S
AU  - Neelapu SS
AUID- ORCID: 0000-0003-1045-4914
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 
      sneelapu@mdanderson.org.
FAU - Dickinson, Michael
AU  - Dickinson M
AUID- ORCID: 0000-0002-1492-5966
AD  - Peter MacCallum Cancer Centre, Royal Melbourne Hospital and The University of 
      Melbourne, Melbourne, Victoria, Australia.
FAU - Munoz, Javier
AU  - Munoz J
AD  - Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
FAU - Ulrickson, Matthew L
AU  - Ulrickson ML
AD  - Banner MD Anderson Cancer Center, Gilbert, AZ, USA.
FAU - Thieblemont, Catherine
AU  - Thieblemont C
AUID- ORCID: 0000-0002-9941-2448
AD  - Universite de Paris, AP-HP, Hopital Saint-Louis, Hemato-oncology, DMU HI, Paris, 
      France.
AD  - Research Unit NF-kappaB, Differenciation et Cancer, Paris, France.
FAU - Oluwole, Olalekan O
AU  - Oluwole OO
AD  - Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
FAU - Herrera, Alex F
AU  - Herrera AF
AD  - City of Hope National Medical Center, Duarte, CA, USA.
FAU - Ujjani, Chaitra S
AU  - Ujjani CS
AD  - Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, 
      WA, USA.
FAU - Lin, Yi
AU  - Lin Y
AD  - Mayo Clinic, Rochester, MN, USA.
FAU - Riedell, Peter A
AU  - Riedell PA
AD  - University of Chicago Medicine, Chicago, IL, USA.
FAU - Kekre, Natasha
AU  - Kekre N
AD  - Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada.
FAU - de Vos, Sven
AU  - de Vos S
AD  - David Geffen School of Medicine at UCLA, Santa Monica, CA, USA.
FAU - Lui, Christine
AU  - Lui C
AD  - Kite, a Gilead Company, Santa Monica, CA, USA.
FAU - Milletti, Francesca
AU  - Milletti F
AD  - Kite, a Gilead Company, Santa Monica, CA, USA.
FAU - Dong, Jinghui
AU  - Dong J
AD  - Kite, a Gilead Company, Santa Monica, CA, USA.
FAU - Xu, Hairong
AU  - Xu H
AD  - Kite, a Gilead Company, Santa Monica, CA, USA.
FAU - Chavez, Julio C
AU  - Chavez JC
AD  - Moffitt Cancer Center, Tampa, FL, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03761056
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20220321
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antigens, CD19)
RN  - 0 (Biological Products)
RN  - U2I8T43Y7R (axicabtagene ciloleucel)
SB  - IM
CIN - Nat Rev Clin Oncol. 2022 May;19(5):283. PMID: 35361894
MH  - Antigens, CD19
MH  - *Biological Products/adverse effects
MH  - Cytokine Release Syndrome
MH  - Humans
MH  - Immunotherapy, Adoptive/adverse effects
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy
MH  - Neoplasm Recurrence, Local
PMC - PMC9018426
COIS- The authors declare the following competing interests: S.S.N., consulting fees or 
      honorarium from Kite, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, 
      Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend 
      Biotech, Adicet Bio, Calibr, Unum Therapeutics, Bluebird Bio, Medscape, Aptitude 
      Health, Bio Ascend and MJH Life Sciences; personal fees from Kite, Merck, Bristol 
      Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision 
      BioSciences, Legend, Adicet Bio, Calibr and Unum Therapeutics; grants, contracts 
      or research funding from Kite, Bristol Myers Squibb, Merck, Poseida, Cellectis, 
      Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, 
      Precision BioSciences, Acerta and Adicet Bio; and intellectual property from 
      Takeda Pharmaceuticals and related to cell therapy. M.D., honoraria from Roche, 
      Gilead, MSD and Novartis; consultancy or advisory role for Roche, Gilead, MSD and 
      Novartis; speakers' bureau participation for Roche, Gilead, MSD and Novartis; and 
      research funding from Novartis and Roche. J.M., honoraria from Targeted Oncology, 
      OncView, Curio, Kyowa Kirin, Physicians' Education Resource and Seagen; 
      consultancy or advisory role for Pharmacyclics/AbbVie, Bayer, Kite, Pfizer, 
      Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa Kirin, Alexion, Fosun Kite, 
      Innovent, Seagen, BeiGene, Debiopharm, Epizyme, Karyopharm, ADC Therapeutics, 
      Servier and Genmab; speakers' bureau participation for Kite, Kyowa, Bayer, 
      Pharmacyclics/Janssen, Seagen, Acrotech/Aurobindo, Beigene, Verastem, 
      AstraZeneca, Celgene/Bristol Myers Squibb and Genentech/Roche; and research 
      funding (payed to institution) from Bayer, Gilead/Kite, Celgene, Merck, Portola, 
      Incyte, Genentech, Pharmacyclics, Seagen, Janssen and Millennium. M.L.U., 
      Advisory Board of Gilead and Stemline. C.T., honoraria from Bristol Myers 
      Squibb/Celgene, AbbVie, Takeda, Novartis, Roche, Kite, and Incyte; consultancy or 
      advisory role for Bristol Myers Squibb/Celgene, AbbVie, Takeda, Roche, Novartis, 
      Kite, and Incyte; and travel support from Bristol Myers Squibb/Celgene, Takeda, 
      Roche, Novartis, and Kite. O.O.O., consultancy or advisory role for Kite, 
      Janssen, Pfizer, Novartis and Curio Science; honoraria and research funding from 
      Kite. A.F.H., consultancy or advisory role for Bristol Meyers Squibb, Merck, 
      Genentech, Seagen, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda and Tubulis; 
      and research funding from Bristol Myers Squibb, Merck, Genentech, Seagen, Kite, 
      Gilead Sciences, AstraZeneca, Karyopharm and ADC Therapeutics. C.S.U., 
      consultancy or advisory role for Atara and Kite; research funding and travel 
      expenses from Kite. Y.L., consultancy or advisory role for Kite, Janssen, 
      Novartis, Celgene, Bluebird Bio, Juno, Legend, Sorrento, Gamida Cell and Vineti; 
      and research funding from Kite, Janssen, Celgene, Bluebird Bio, Merck and Takeda. 
      P.A.R., honoraria from Novartis; consultancy or advisory role for Novartis, 
      Celgene/Bristol Myers Squibb, Takeda, BeiGene and Karyopharm Therapeutics; 
      speakers' bureau participation for Kite; and research funding from Kite, 
      Celgene/Bristol Myers Squibb, Novartis, Calibr, Xencor, MorphoSys and Tessa 
      Therapeutics. N.K., consulting or advisory role and honoraria from Gilead, 
      Novartis and Celgene. S.d.V., participation on a Data Safety Advisory Board for 
      BeiGene. C.L., employment with and travel support from Kite; stock or other 
      ownership in Gilead Sciences. F.M., employment with Kite; and stock or other 
      ownership in Gilead. J.D., employment with Kite; stock or other ownership in 
      Gilead Sciences; consultancy or advisory role for and intellectual property from 
      GliaCure/Tufts. H.X., employment with Kite. J.C.C., consultancy fees for Kite, 
      AbbVie, Janssen, ADC Therapeutics, Karyopharm, Kymera, GenMab and Novartis; 
      speakers' bureau participation for Morphosys, Epyzime, Bristol Myers Squibb, 
      BeiGene and AstraZeneca; and research funding from AstraZeneca, Merck, ADC 
      Therapeutics and Adaptive.
EDAT- 2022/03/23 06:00
MHDA- 2022/04/22 06:00
PMCR- 2022/03/21
CRDT- 2022/03/22 05:37
PHST- 2021/10/29 00:00 [received]
PHST- 2022/02/01 00:00 [accepted]
PHST- 2022/01/26 00:00 [revised]
PHST- 2022/03/23 06:00 [pubmed]
PHST- 2022/04/22 06:00 [medline]
PHST- 2022/03/22 05:37 [entrez]
PHST- 2022/03/21 00:00 [pmc-release]
AID - 10.1038/s41591-022-01731-4 [pii]
AID - 1731 [pii]
AID - 10.1038/s41591-022-01731-4 [doi]
PST - ppublish
SO  - Nat Med. 2022 Apr;28(4):735-742. doi: 10.1038/s41591-022-01731-4. Epub 2022 Mar 
      21.