PMID- 30572922
OWN - NLM
STAT- MEDLINE
DCOM- 20200109
LR  - 20200309
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 11
IP  - 1
DP  - 2018 Dec 20
TI  - A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell 
      therapy directed against B cell maturation antigen, in patients with relapsed or 
      refractory multiple myeloma.
PG  - 141
LID - 10.1186/s13045-018-0681-6 [doi]
LID - 141
AB  - BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated 
      proven efficacy in some hematologic cancers. We evaluated the safety and efficacy 
      of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 
      distinct B cell maturation antigen epitopes, in patients with relapsed/refractory 
      (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, 
      open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. 
      Lymphodepletion was performed using cyclophosphamide 300 mg/m(2). LCAR-B38M CAR T 
      cells (median CAR+ T cells, 0.5 x 10(6) cells/kg [range, 0.07 to 2.1 x 10(6)]) 
      were infused in 3 separate infusions. The primary objective is to evaluate the 
      safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the 
      antimyeloma response of the treatment based on the general guidelines of the 
      International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had 
      received LCAR-B38M CAR T cells. All patients experienced >/= 1 adverse events 
      (AEs). Grade >/= 3 AEs were reported in 37/57 patients (65%); most common were 
      leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate 
      aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 
      51/57 patients (90%); 4/57 (7%) had grade >/= 3 cases. One patient reported 
      neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The 
      overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 
      patients (68%) achieved a complete response, 3/57 (5%) achieved a very good 
      partial response, and 8/57 (14%) achieved a partial response. Minimal residual 
      disease was negative for 36/57 (63%) patients. The median time to response was 
      1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median 
      progression-free survival was 15 months (95% CI, 11 to not estimable). Median 
      overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T 
      cell therapy displayed a manageable safety profile and demonstrated deep and 
      durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov 
      , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
FAU - Zhao, Wan-Hong
AU  - Zhao WH
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Liu, Jie
AU  - Liu J
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Wang, Bai-Yan
AU  - Wang BY
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Chen, Yin-Xia
AU  - Chen YX
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Cao, Xing-Mei
AU  - Cao XM
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Yang, Yun
AU  - Yang Y
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Zhang, Yi-Lin
AU  - Zhang YL
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Wang, Fang-Xia
AU  - Wang FX
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Zhang, Peng-Yu
AU  - Zhang PY
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Lei, Bo
AU  - Lei B
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Gu, Liu-Fang
AU  - Gu LF
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Wang, Jian-Li
AU  - Wang JL
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Yang, Nan
AU  - Yang N
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Zhang, Ru
AU  - Zhang R
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Shen, Ying
AU  - Shen Y
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Bai, Ju
AU  - Bai J
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Xu, Yan
AU  - Xu Y
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Wang, Xu-Geng
AU  - Wang XG
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Zhang, Rui-Li
AU  - Zhang RL
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Wei, Li-Li
AU  - Wei LL
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
FAU - Li, Zong-Fang
AU  - Li ZF
AD  - National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, 
      The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, 
      ShaanXi, China.
FAU - Li, Zhen-Zhen
AU  - Li ZZ
AD  - National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, 
      The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, 
      ShaanXi, China.
FAU - Geng, Yan
AU  - Geng Y
AD  - Department of Clinical Laboratory, The Second Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, 710004, ShaanXi, China.
FAU - He, Qian
AU  - He Q
AD  - Department of Clinical Laboratory, The Second Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, 710004, ShaanXi, China.
FAU - Zhuang, Qiu-Chuan
AU  - Zhuang QC
AD  - Nanjing Legend Biotech Inc., Nanjing, 210000, Jiangsu, China.
FAU - Fan, Xiao-Hu
AU  - Fan XH
AD  - Nanjing Legend Biotech Inc., Nanjing, 210000, Jiangsu, China.
FAU - He, Ai-Li
AU  - He AL
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China.
AD  - National-Local Joint Engineering Research Center of Biodiagnostics & Biotherapy, 
      The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, 
      ShaanXi, China.
FAU - Zhang, Wang-Gang
AU  - Zhang WG
AD  - Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong 
      University, 157 West 5th Road, Xi'an, 710004, ShaanXi, China. 
      zhangwanggang2003@yahoo.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT03090659
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20181220
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (B-Cell Maturation Antigen)
RN  - 0 (Receptors, Chimeric Antigen)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - B-Cell Maturation Antigen/*metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy/pathology
MH  - Receptors, Chimeric Antigen/*metabolism
MH  - Remission Induction
MH  - Young Adult
PMC - PMC6302465
OTO - NOTNLM
OT  - BCMA
OT  - CAR T
OT  - Chimeric antigen receptor
OT  - Multiple myeloma
OT  - Refractory
OT  - Relapsed
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was performed in 
      accordance with the Declaration of Helsinki and was approved by the institutional 
      independent ethics committee (reference number: 2016002) of The Second Affiliated 
      Hospital of Xi'an Jiaotong University. All patients provided written informed 
      consent. CONSENT FOR PUBLICATION: Consent from patients whose data are included 
      in this article has been obtained in writing. COMPETING INTERESTS: Q-CZ and X-HF 
      are employees of Nanjing Legend Biotech Co. All other authors declare that they 
      have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral 
      with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2018/12/24 06:00
MHDA- 2020/01/10 06:00
PMCR- 2018/12/20
CRDT- 2018/12/22 06:00
PHST- 2018/11/14 00:00 [received]
PHST- 2018/11/23 00:00 [accepted]
PHST- 2018/12/22 06:00 [entrez]
PHST- 2018/12/24 06:00 [pubmed]
PHST- 2020/01/10 06:00 [medline]
PHST- 2018/12/20 00:00 [pmc-release]
AID - 10.1186/s13045-018-0681-6 [pii]
AID - 681 [pii]
AID - 10.1186/s13045-018-0681-6 [doi]
PST - epublish
SO  - J Hematol Oncol. 2018 Dec 20;11(1):141. doi: 10.1186/s13045-018-0681-6.