期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 19, 页码 9543-9551出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1819745116
关键词
multiple myeloma; chimeric antigen receptor modified T cells; biepitope; BCMA; cytokine release syndrome
资金
- 111 Project [B17029]
- Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research [2019CXJQ01]
- Chinese National Key Basic Research Project 973 [2013CB966800]
- National Key Research and Development Program [2016YFC0902800]
- National Science Foundation of China [81670147, 81800099]
- Academic Leader Program of the Shanghai Science and Technology Committee [16XD1402000]
- Shanghai Rising-Star Program [17QA1402200, 19QA1407800]
- Shanghai Excellent Youth Medical Talents Training Program [2018YQ09]
- National Science and Technology Major Project [2018ZX09101001, 2018ZX09301052002]
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.
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