PMID- 36542826
OWN - NLM
STAT- MEDLINE
DCOM- 20230410
LR  - 20231119
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 141
IP  - 14
DP  - 2023 Apr 6
TI  - Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: 
      primary analysis of the phase 3 TRANSFORM study.
PG  - 1675-1684
LID - 10.1182/blood.2022018730 [doi]
AB  - This global phase 3 study compared lisocabtagene maraleucel (liso-cel) with a 
      standard of care (SOC) as second-line therapy for primary refractory or early 
      relapsed (</=12 months) large B-cell lymphoma (LBCL). Adults eligible for 
      autologous stem cell transplantation (ASCT; N = 184) were randomly assigned in a 
      1:1 ratio to liso-cel (100 x 106 chimeric antigen receptor-positive T cells) or 
      SOC (3 cycles of platinum-based immunochemotherapy followed by high-dose 
      chemotherapy and ASCT in responders). The primary end point was event-free 
      survival (EFS). In this primary analysis with a 17.5-month median follow-up, 
      median EFS was not reached (NR) for liso-cel vs 2.4 months for SOC. Complete 
      response (CR) rate was 74% for liso-cel vs 43% for SOC (P < .0001) and median 
      progression-free survival (PFS) was NR for liso-cel vs 6.2 months for SOC (hazard 
      ratio [HR] = 0.400; P < .0001). Median overall survival (OS) was NR for liso-cel 
      vs 29.9 months for SOC (HR = 0.724; P = .0987). When adjusted for crossover from 
      SOC to liso-cel, 18-month OS rates were 73% for liso-cel and 54% for SOC (HR = 
      0.415). Grade 3 cytokine release syndrome and neurological events occurred in 1% 
      and 4% of patients in the liso-cel arm, respectively (no grade 4 or 5 events). 
      These data show significant improvements in EFS, CR rate, and PFS for liso-cel 
      compared with SOC and support liso-cel as a preferred second-line treatment 
      compared with SOC in patients with primary refractory or early relapsed LBCL. 
      This trial was registered at www.clinicaltrials.gov as #NCT03575351.
CI  - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Abramson, Jeremy S
AU  - Abramson JS
AUID- ORCID: 0000-0001-8467-9257
AD  - Massachusetts General Hospital Cancer Center, Harvard Medical School, Harvard 
      University, Boston, MA.
FAU - Solomon, Scott R
AU  - Solomon SR
AD  - Transplant and Cellular Immunotherapy Program, Northside Hospital Cancer 
      Institute, Atlanta, GA.
FAU - Arnason, Jon
AU  - Arnason J
AD  - Department of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, 
      MA.
FAU - Johnston, Patrick B
AU  - Johnston PB
AD  - Division of Hematology, Mayo Clinic, Rochester, MN.
FAU - Glass, Bertram
AU  - Glass B
AD  - Department of Hematology and Cell Therapy, Helios Klinikum Berlin-Buch, Berlin, 
      Germany.
FAU - Bachanova, Veronika
AU  - Bachanova V
AD  - Division of Hematology, Oncology and Transplantation, University of Minnesota, 
      Minneapolis, MN.
FAU - Ibrahimi, Sami
AU  - Ibrahimi S
AD  - Transplant and Cellular Therapy Clinic, University of Oklahoma Stephenson Cancer 
      Center, Oklahoma City, OK.
FAU - Mielke, Stephan
AU  - Mielke S
AUID- ORCID: 0000-0002-8325-9215
AD  - Departments of Laboratory Medicine and Medicine at Huddinge, Center of Allogeneic 
      Stem Cell Transplantation and Cellular Therapy, Karolinska Institutet and 
      University Hospital, Karolinska Comprehensive Cancer Center, Stockholm, Sweden.
FAU - Mutsaers, Pim
AU  - Mutsaers P
AD  - Department of Hematology, Erasmus University Medical Center, Rotterdam, The 
      Netherlands.
FAU - Hernandez-Ilizaliturri, Francisco
AU  - Hernandez-Ilizaliturri F
AD  - Department of Hematologic Oncology, Roswell Park Comprehensive Cancer Center, 
      Buffalo, NY.
FAU - Izutsu, Koji
AU  - Izutsu K
AD  - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Morschhauser, Franck
AU  - Morschhauser F
AUID- ORCID: 0000-0002-3714-9824
AD  - Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes 
      Injectables et les Technologies Associees, Lille, France.
FAU - Lunning, Matthew
AU  - Lunning M
AD  - Hematology/Oncology Division, University of Nebraska Medical Center, Omaha, NE.
FAU - Crotta, Alessandro
AU  - Crotta A
AD  - Celgene, a Bristol-Myers Squibb Company, Boudry, Switzerland.
FAU - Montheard, Sandrine
AU  - Montheard S
AD  - Celgene, a Bristol-Myers Squibb Company, Boudry, Switzerland.
FAU - Previtali, Alessandro
AU  - Previtali A
AD  - Celgene, a Bristol-Myers Squibb Company, Boudry, Switzerland.
FAU - Ogasawara, Ken
AU  - Ogasawara K
AUID- ORCID: 0000-0002-4264-8927
AD  - Bristol Myers Squibb, Princeton, NJ.
FAU - Kamdar, Manali
AU  - Kamdar M
AD  - Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation, 
      University of Colorado Cancer Center, Aurora, CO.
LA  - eng
SI  - ClinicalTrials.gov/NCT03575351
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antigens, CD19)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Antineoplastic Combined Chemotherapy Protocols
MH  - Transplantation, Autologous
MH  - *Lymphoma, Large B-Cell, Diffuse/drug therapy
MH  - Proportional Hazards Models
MH  - Immunotherapy, Adoptive/adverse effects
MH  - Antigens, CD19/therapeutic use
PMC - PMC10646768
COIS- Conflict-of-interest disclosure: J.S.A. reports consulting fees from Bristol 
      Myers Squibb (BMS), AbbVie, Genentech, Epizyme, BeiGene, Kymera, bluebird bio, 
      Incyte, Kite Pharma, Genmab, Ono Pharmaceutical, Mustang Bio, MorphoSys, 
      Regeneron, Century, AstraZeneca, Eli Lilly, and Janssen and received research 
      funding from BMS and Seattle Genetics. J.A. reports honoraria from BMS. B.G. is a 
      consultant for BMS, Roche, Gilead, and Novartis; reports research funding from 
      Roche; is a part of speaker's bureau at BMS, Roche, and Novartis; is on the 
      advisory boards of BMS and Roche; and is a current employee of Helios Klinikum 
      Berlin-Buch. S.I. is an equity holder in Karyopharm Therapeutics. S. Mielke 
      reports honoraria from Novartis and Celgene, a Bristol-Myers Squibb Company; 
      travel support from Kite/Gilead; and is on the data safety monitoring boards for 
      Miltenyi Biotec and Immunicum. P.M. reports grants or contracts from AstraZeneca 
      and consultancy fees from GlaxoSmithKline. F.H.-I. is on the advisory boards of 
      Kite; Novartis; Celgene, a Bristol-Myers Squibb Company; BMS; Epizyme; Incyte; 
      and AbbVie. K.I. reports consulting fees from BMS, BeiGene, AstraZeneca, Ono 
      Pharmaceutical, AbbVie, Novartis, and Chugai; honoraria from BMS, AstraZeneca, 
      Ono Pharmaceutical, AbbVie, Novartis, Chugai, MSD, Eisai, Janssen, Kyowa Kirin, 
      Daiichi Sankyo, Eli Lilly, SymBio Pharmaceuticals Limited, and Takeda; and 
      research funding from BeiGene, AstraZeneca, Ono Pharmaceutical, AbbVie, Chugai, 
      MSD, Eisai, Incyte, Janssen, Yakult Pharmaceutical Industry Co, Ltd, Daiichi 
      Sankyo, Loxo Oncology, and Genmab. F.M. reports consulting fees from Roche, 
      Gilead, and AbbVie and membership on an entity's board of directors or advisory 
      committees for Roche, Gilead, Novartis, BMS, AbbVie, Genmab, Miltenyi Biotec, 
      Allogene Therapeutics, AstraZeneca, and Janssen. M.L. reports consulting fees 
      from AbbVie, Acrotech Biopharma, ADC Therapeutics, Astellas, AstraZeneca, BMS, 
      Daiichi Sankyo, EUSA Pharma, Fate Therapeutics, Genentech, Genmab, 
      Janssen/Pharmacyclics, Kite, MorphoSys, Nurix Therapeutics, Pharmacyclics, 
      Seattle Genetics, and TG Therapeutics and research funding from BMS and Curis. 
      A.C. and A.P. are current employees of Celgene, a Bristol-Myers Squibb Company 
      and current equity holders in BMS. S. Montheard is a current employee of Celgene, 
      a Bristol-Myers Squibb Company and a current equity holder in BMS, Novartis 
      Pharma AG, and Alcon. K.O. is a current employee of BMS and current equity holder 
      in BMS. M.K. reports consulting fees from TG Therapeutics, Genentech, AbbVie, 
      AstraZeneca, Adaptive Technologies, ADC Therapeutics, BeiGene, and ImpactBio; 
      reports honoraria from Seagen; and reports research funding and/or data 
      monitoring committee from TG Therapeutics, Genentech, Novartis, and Celgene, a 
      Bristol-Myers Squibb Company. The remaining authors declare no competing 
      financial interests.
EDAT- 2022/12/22 06:00
MHDA- 2023/04/10 06:42
PMCR- 2022/12/23
CRDT- 2022/12/21 16:12
PHST- 2022/12/12 00:00 [accepted]
PHST- 2022/10/24 00:00 [received]
PHST- 2023/04/10 06:42 [medline]
PHST- 2022/12/22 06:00 [pubmed]
PHST- 2022/12/21 16:12 [entrez]
PHST- 2022/12/23 00:00 [pmc-release]
AID - S0006-4971(22)08446-4 [pii]
AID - 10.1182/blood.2022018730 [doi]
PST - ppublish
SO  - Blood. 2023 Apr 6;141(14):1675-1684. doi: 10.1182/blood.2022018730.