Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review
10.3760/cma.j.issn.0253-2727.2019.08.005
- VernacularTitle: 同种异基因CAR-T细胞治疗复发/难治多发性骨髓瘤四例临床观察并文献复习
- Author:
Lingzhi YAN
1
;
Jingjing SHANG
1
;
Xiaolan SHI
1
;
Su QU
2
;
Liqing KANG
2
;
Nan XU
2
;
Weirong CHANG
1
;
Lei YU
2
;
Depei WU
1
;
Chengcheng FU
1
Author Information
1. The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Suzhou 215006, China
2. Shanghai Unicar-Therapy Biomed-Phamaceutical Technology CO, LTD, Shanghai 201203, China
- Publication Type:Journal Article
- Keywords:
Multiple myeloma;
Relapsed and/or refractory;
Chimeric antigen receptor T cell immunotherapy
- From:
Chinese Journal of Hematology
2019;40(8):650-655
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) .
Methods:CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×107/kg on day 0) and (4.0-6.8) ×107/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique.
Results:CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days.
Conclusions:Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.
