Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.

Authors:
Jie Xu
Jie Xu
College of Food Science and Engineering
Columbus | United States
Shuang-Shuang Yang
Shuang-Shuang Yang
Fudan University
China
Yan Sun
Yan Sun
National Institute on Drug Dependence
Rockville | United States
Wen Wu
Wen Wu
Yonsei University College of Medicine
South Korea
Yuan-Fang Liu
Yuan-Fang Liu
Shanghai Institute of Hematology
China
Ji Xu
Ji Xu
Jiangsu Province Hospital
China
Yan Zhuang
Yan Zhuang
The University of Texas MD Anderson Cancer Center

Proc Natl Acad Sci U S A 2019 May 15;116(19):9543-9551. Epub 2019 Apr 15.

State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, 200025 Shanghai, China;

Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1819745116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510991PMC
May 2019
2 Reads
9.809 Impact Factor

Article Mentions


Provided by Crossref Event Data
twitter
Twitter:
April 20, 2019, 2:57 am EST
twitter
Twitter:
April 20, 2019, 12:56 am EST
twitter
Twitter:
April 19, 2019, 11:06 pm EST
twitter
Twitter:
April 19, 2019, 9:17 pm EST
twitter
Twitter:
April 19, 2019, 5:37 pm EST
twitter
Twitter:
April 19, 2019, 5:06 pm EST
twitter
Twitter:
April 19, 2019, 4:54 pm EST
twitter
Twitter:
April 19, 2019, 3:47 pm EST
twitter
Twitter:
April 19, 2019, 2:18 pm EST
twitter
Twitter:
April 19, 2019, 11:25 am EST
twitter
Twitter:
April 19, 2019, 10:50 am EST
twitter
Twitter:
April 19, 2019, 10:35 am EST
twitter
Twitter:
April 19, 2019, 10:33 am EST
twitter
Twitter:
April 19, 2019, 10:31 am EST
twitter
Twitter:
April 19, 2019, 10:30 am EST
twitter
Twitter:
April 19, 2019, 10:30 am EST
twitter
Twitter:
April 19, 2019, 10:23 am EST
twitter
Twitter:
April 19, 2019, 10:17 am EST
twitter
Twitter:
April 19, 2019, 10:16 am EST
twitter
Twitter:
April 19, 2019, 10:15 am EST
twitter
Twitter:
April 19, 2019, 10:15 am EST
twitter
Twitter:
April 19, 2019, 10:15 am EST
twitter
Twitter:
April 17, 2019, 1:28 pm EST
twitter
Twitter:
April 17, 2019, 12:08 pm EST
twitter
Twitter:
April 17, 2019, 10:28 am EST

Publication Analysis

Top Keywords

car cells
12
cell maturation
8
maturation antigen
8
biepitopic car
8
multiple myeloma
8
car cell
8
car
8
cases response
8
cases
6
response
6
response rate
4
rate 882%
4
882% achieving
4
crs cases
4
il-6 key
4
key indicators
4
indicators severe
4
severe crs
4
achieving stringent
4
vgpr nonresponder
4

Similar Publications