PMID- 37710005
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20240517
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 29
IP  - 10
DP  - 2023 Oct
TI  - Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma 
      ineligible for autologous stem cell transplantation: a phase 2 trial.
PG  - 2593-2601
LID - 10.1038/s41591-023-02572-5 [doi]
AB  - Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to 
      standard of care as second-line therapy in patients with high-risk 
      relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for 
      autologous stem cell transplantation (ASCT); however, in clinical practice, 
      roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. 
      The efficacy of axi-cel remains to be ascertained in transplant-ineligible 
      patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a 
      second-line therapy in 62 patients with R/R LBCL who were considered ineligible 
      for ASCT. The primary end point was investigator-assessed complete metabolic 
      response at 3 months from the axi-cel infusion. Key secondary end points included 
      progression-free survival, overall survival and safety. The study met its primary 
      end point with a complete metabolic response of 71.0% (95% confidence interval, 
      58.1-81.8%) at 3 months. With a median follow-up of 12.0 months (range, 
      2.1-17.9), median progression-free survival was 11.8 months (95% confidence 
      interval, 8.4-not reached) and overall survival was not reached. There was no 
      unexpected toxicity. Grade 3-4 cytokine release syndrome and neurologic events 
      occurred in 8.1% and 14.5% of patients, respectively. These results support 
      axi-cel as second-line therapy in patients with R/R LBCL ineligible for ASCT. 
      ClinicalTrials.gov Identifier: NCT04531046 .
CI  - (c) 2023. The Author(s).
FAU - Houot, Roch
AU  - Houot R
AUID- ORCID: 0000-0003-1729-8213
AD  - Department of Hematology, University Hospital of Rennes, UMR U1236, INSERM, 
      University of Rennes, French Blood Establishment, Rennes, France. 
      roch.houot@chu-rennes.fr.
FAU - Bachy, Emmanuel
AU  - Bachy E
AUID- ORCID: 0000-0003-2694-7510
AD  - Department of Hematology, Lyon Sud Hospital Center, INSERM U1111, Lyon, France.
FAU - Cartron, Guillaume
AU  - Cartron G
AD  - Department of Hematology, University Hospital of Montpellier, UMR-CNRS 5535, 
      Montpellier, France.
FAU - Gros, Francois-Xavier
AU  - Gros FX
AUID- ORCID: 0000-0001-8998-3039
AD  - Department of Clinical Hematology and Cellular Therapy, University Hospital of 
      Bordeaux, Bordeaux, France.
FAU - Morschhauser, Franck
AU  - Morschhauser F
AD  - ULR 7365 - GRITA, University Hospital of Lille, Lille, France.
FAU - Oberic, Lucie
AU  - Oberic L
AD  - Department of Hematology, Cancer University Institute of Toulouse Oncopole, 
      Toulouse, France.
FAU - Gastinne, Thomas
AU  - Gastinne T
AD  - Department of Hematology, University Hospital of Nantes, Nantes, France.
FAU - Feugier, Pierre
AU  - Feugier P
AD  - Department of Hematology, University Hospital of Nancy, INSERM 1256, University 
      of Lorraine, Vandoeuvre-les-Nancy, France.
FAU - Dulery, Remy
AU  - Dulery R
AD  - Department of Clinical Hematology and Cellular Therapy, Sorbonne University, 
      Saint-Antoine Hospital, AP-HP, INSERM UMR938, Paris, France.
FAU - Thieblemont, Catherine
AU  - Thieblemont C
AUID- ORCID: 0000-0002-9941-2448
AD  - Department of Hematology and Oncology, Saint-Louis Hospital, AP-HP, Paris, 
      France.
FAU - Joris, Magalie
AU  - Joris M
AD  - Department of Hematology, University Hospital of Amiens, Amiens, France.
FAU - Jardin, Fabrice
AU  - Jardin F
AUID- ORCID: 0000-0002-6804-7943
AD  - Department of Clinical Hematology, Henri Becquerel Center, INSERM U1245, Rouen, 
      France.
FAU - Choquet, Sylvain
AU  - Choquet S
AUID- ORCID: 0000-0002-7791-0470
AD  - Department of Hematology, University Hospital Pitie Salpetriere, AP-HP, Sorbonne 
      University, Paris, France.
FAU - Casasnovas, Olivier
AU  - Casasnovas O
AD  - Department of Clinical Hematology, Dijon University Hospital, INSERM UMR1231, 
      Dijon, France.
FAU - Brisou, Gabriel
AU  - Brisou G
AD  - Department of Hematology, Institut Paoli-Calmettes, Marseille, France.
FAU - Cheminant, Morgane
AU  - Cheminant M
AD  - Department of Clinical Hematology, Necker-Enfants Malades University Hospital, 
      AP-HP, INSERM UMR1163, Paris, France.
FAU - Bay, Jacques-Olivier
AU  - Bay JO
AD  - Department of Clinical Hematology and Cellular Therapy, Clermont-Ferrand 
      University Hospital Center, Clermont-Ferrand, France.
FAU - Gutierrez, Francisco Llamas
AU  - Gutierrez FL
AD  - Department of Anatomopathology, University Hospital of Rennes, Rennes, France.
FAU - Menard, Cedric
AU  - Menard C
AD  - French Blood Establishment and SITI Laboratory, UMR U1236, INSERM, University of 
      Rennes, University Hospital Center of Rennes, Rennes, France.
FAU - Tarte, Karin
AU  - Tarte K
AUID- ORCID: 0000-0002-6809-917X
AD  - French Blood Establishment and SITI Laboratory, UMR U1236, INSERM, University of 
      Rennes, University Hospital Center of Rennes, Rennes, France.
FAU - Delfau, Marie-Helene
AU  - Delfau MH
AD  - Department of Immunology, Henri Mondor Hospital, Creteil, France.
FAU - Portugues, Cedric
AU  - Portugues C
AD  - Department of Biostatistics, LYSARC, Lyon-Sud Hospital, Pierre-Benite, France.
FAU - Itti, Emmanuel
AU  - Itti E
AD  - Department of Nuclear Medicine, Henri Mondor Hospital, Creteil, France.
FAU - Palard-Novello, Xavier
AU  - Palard-Novello X
AD  - Department of Nuclear Medicine, University of Rennes, CLCC Eugene Marquis, 
      INSERM, Rennes, France.
FAU - Blanc-Durand, Paul
AU  - Blanc-Durand P
AD  - Department of Nuclear Medicine, CHU H. Mondor, U-PEC, AP-HP, Creteil, France.
FAU - Al Tabaa, Yassine
AU  - Al Tabaa Y
AD  - Scintidoc Nuclear Medicine Center, Clinique Clementville, Montpellier, France.
FAU - Bailly, Clement
AU  - Bailly C
AD  - Nantes-Angers Cancer Research Center CRCI2NA, University of Nantes, INSERM 
      UMR1307, CNRS-ERL6075, Nantes, France.
FAU - Laurent, Camille
AU  - Laurent C
AUID- ORCID: 0000-0002-5375-7512
AD  - Department of Pathology, Cancer University Institute of Toulouse Oncopole, CHU 
      Toulouse, CRCT INSERM U1037, Toulouse, France.
FAU - Lemonnier, Francois
AU  - Lemonnier F
AD  - Lymphoid Malignancies Unit, Henri Mondor Hospital, Mondor Institute for 
      Biomedical Research, INSERM U955, University Paris-Est, Creteil, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT04531046
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230914
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - U2I8T43Y7R (axicabtagene ciloleucel)
RN  - 0 (Biological Products)
RN  - 0 (Antigens, CD19)
SB  - IM
EIN - Nat Med. 2023 Oct 9;:. PMID: 37814064
EIN - Nat Med. 2024 May 14;:. PMID: 38745012
MH  - Humans
MH  - Transplantation, Autologous
MH  - *Hematopoietic Stem Cell Transplantation
MH  - *Lymphoma, Large B-Cell, Diffuse/therapy
MH  - *Biological Products/therapeutic use
MH  - Cytokine Release Syndrome
MH  - Immunotherapy, Adoptive/adverse effects
MH  - Antigens, CD19
PMC - PMC10579056
COIS- R.H. has received honoraria from Kite/Gilead, Novartis, Incyte, Janssen, MSD, 
      Takeda and Roche; and is a member on an entity's Board of Directors or advisory 
      committees of Kite/Gilead, Novartis, Bristol-Myers Squibb/Celgene, ADC 
      Therapeutics, Incyte and Miltenyi. E.B. has received honoraria from Kite/Gilead, 
      Bristol-Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics, Roche and 
      Takeda; travel reimbursement from Kite/Gilead, Bristol-Myers Squibb, Novartis and 
      Pfizer; and research funding from Amgen and Bristol-Myers Squibb. G.C. has 
      received consulting fees from Roche, AbbVie, Bristol-Myers Squibb, MedXCell, 
      Mabqi and Onward Therapeutics; honoraria from Jansen, Gilead, Novartis, Roche, 
      Bristol-Myers Squibb and Incyte; and travel and accommodation expenses from 
      Gilead, Roche and Jansen. F.X.G. has received consulting fees from Gilead, 
      Bristol-Myers Squibb, Miltenyi and Novartis; and travel and accommodation 
      expenses from Gilead and Novartis. F.M. has received consulting fees from Roche, 
      Gilead, Novartis, Bristol-Myers Squibb, Genmab and AbbVie; and honoraria for 
      advisory boards from Roche, Gilead and Miltenyi. L.O. has received consulting 
      fees from Roche; honoraria from Bristol-Myers Squibb, Kite/Gilead and Incyte; and 
      travel and accommodation expenses from Roche and AstraZeneca. T.G. has received 
      consulting fees from Takeda and Kite/Gilead; honoraria from Kite/Gilead; and 
      travel and accommodation expenses from Roche, Takeda and Kite/Gilead. P.F. has 
      received consulting fees from Gilead, AstraZeneca, BeiGene, AbbVie and Janssen; 
      honoraria from Gilead, AstraZeneca, BeiGene, AbbVie and Janssen; and travel and 
      accommodation expenses from Gilead, AstraZeneca, BeiGene, AbbVie and Janssen. 
      R.D. has received honoraria from Novartis and Takeda; research funding from Ligue 
      contre le Cancer, Arthur Sachs, Monahan Foundation, Servier Foundation, Philippe 
      Foundation and DCP AP-HP; and non-financial support from Kite/Gilead. C.T. has 
      received institutional research funding from Kite/Gilead and Roche; honoraria for 
      advisory boards from Roche, Novartis, AstraZeneca, BeiGene, AbbVie, Takeda, 
      Roche, Novartis, Kite/Gilead, Bristol-Myers Squibb; and travel and accommodation 
      expenses from Roche, Novartis, AbbVie, Takeda, Roche, Kite/Gilead and 
      Bristol-Myers Squibb. F.J. has received honoraria from Roche, Gilead, Janssen and 
      Bristol-Myers Squibb; honoraria for advisory boards from Roche; and travel and 
      accommodation expenses from Roche and Gilead. S.C. has received consulting fees 
      from Atara, Novartis, Kite/Gilead, Pierre Fabre, Takeda, AbbVie and AstraZeneca; 
      honoraria for advisory boards from Kite/Gilead, Novartis, AbbVie, Takeda and 
      Viatris; institutional funding from Janssen; and travel and accommodation 
      expenses from Novartis, AbbVie and Pierre Fabre. O.C. has received honoraria from 
      Roche, Takeda, Bristol-Myers Squibb, Merck, Kite/Gilead, AbbVie and ADC 
      Therapeutics; and research funding from Roche, Takeda and Kite/Gilead. G.B. has 
      received honoraria for advisory boards from Novartis, Kite/Gilead, Bristol-Myers 
      Squibb and Incyte; and travel and accommodation expenses from Novartis, 
      Kite/Gilead, Bristol-Myers Squibb and Incyte. M.C. has received institutional 
      research funding from AP-HP, INSERM, INCA, Fondation ARC pour la Recherche sur le 
      Cancer and CALYM; honoraria from Amgen and CSL Behring; research funding from 
      Innate Pharma and Servier; and travel and accommodation expenses from Pfizer, 
      Grifols, CSL Behring and Gilead. F.L.G. has received honoraria from Rennes 
      University Hospital. C.M. has received research funding from Kite 
      Pharmaceuticals. C.P. is a LYSARC employee. E.I. has received honoraria from 
      Janssen-Cilag and Pfizer. C.L. has received research funding from Ligue contre le 
      Cancer and Labex Toucan; and travel and accommodation expenses from Roche and 
      Janssen. All other authors declare no competing interests.
EDAT- 2023/09/15 00:42
MHDA- 2023/10/23 01:18
PMCR- 2023/09/14
CRDT- 2023/09/14 23:32
PHST- 2023/05/25 00:00 [received]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2023/10/23 01:18 [medline]
PHST- 2023/09/15 00:42 [pubmed]
PHST- 2023/09/14 23:32 [entrez]
PHST- 2023/09/14 00:00 [pmc-release]
AID - 10.1038/s41591-023-02572-5 [pii]
AID - 2572 [pii]
AID - 10.1038/s41591-023-02572-5 [doi]
PST - ppublish
SO  - Nat Med. 2023 Oct;29(10):2593-2601. doi: 10.1038/s41591-023-02572-5. Epub 2023 
      Sep 14.