Comparison of single infusion of anti-BCMA versus combined infusion of anti-CD19 chimeric antigen receptor T cells for immune reconstruction in relapsed/refractory multiple myeloma
10.3760/cma.j.issn.0253-2727.2021.09.004
- VernacularTitle:单纯输注抗BCMA与抗BCMA输注联合抗CD19嵌合抗原受体T细胞治疗复发/难治性多发性骨髓瘤免疫重建的对比
- Author:
Jiao GE
1
;
Tingting ZHAO
;
Chongyang WAN
;
Jieyun XIA
;
Siyi GUO
;
Mingxiao YU
;
Juan CHEN
;
Ying WANG
;
Kailin XU
;
Zhenyu LI
Author Information
1. 徐州医科大学附属医院血液科 221002
- Keywords:
Chimeric antigen receptor T cells;
Multiple myeloma;
Immune reconstruction
- From:
Chinese Journal of Hematology
2021;42(9):733-738
- CountryChina
- Language:Chinese
-
Abstract:
Objective:We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen (BCMA) , chimeric antigen receptor T cells (CAR-T) , and combined infusion of anti-CD19 CAR-T cells in the treatment of recurrent/refractory multiple myeloma (RRMM) .Methods:Sixty-one patients with RRMM who underwent CAR-T cell therapy in our hospital from June 2017 to December 2020 were selected. Among them, 26 patients received anti-BCMA target, and 35 patients received anti-BCMA combined with anti-CD19 target. Using flow cytometry, we determined T cell subsets (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) , B cells (CD19 +) , and NK cells (CD16 + CD56 +) at different time points before and after CAR-T treatment, and detected immunoglobulin IgG, IgA and IgM levels by immunoturbidimetry. We compared the reconstruction rules of lymphocyte subsets and immunoglobulins in the two groups. Results:CD8 + T lymphocytes recovered most rapidly after the infusion of CAR-T cells, returning to pre-infusion levels at 3 months and 1 month after infusion, respectively[BCMA: 695 (357, 1264) /μl vs 424 (280, 646) /μl; BCMA+CD19: 546 (279, 1672) /μl vs 314 (214, 466) /μl]. NK cells returned to normal levels at 3 months after infusion in both groups[BCMA: 171 (120, 244) /μl, BCMA+CD19: 153 (101, 218) /μl (Normal reference range 150-1100/μl) ]; however, the NK cells were not maintained at stable levels in the BCMA CAR-T cells group. The recovery of CD4 + T lymphocytes in both groups was slow and remained persistently low within 12 months after infusion, and no recovery was observed in most patients. The reversal of the ratio of CD4 +/CD8 + lasted for more than a year. The levels of CD19 + B cells in both groups returned to baseline 3 months after infusion[BCMA: 62 (10, 72) /μl vs 57 (24, 78) /μl; BCMA+CD19: 40 (4, 94) /μl vs 29 (14, 46) /μl]. IgG returned to the pre-infusion level 12 months after infusion in the group with anti-BCMA cells alone, but not in the group with combined infusion of CD19 CAR T cells[7.82 (6.03, 9.64) g/L vs 6.92 (4.62, 12.76) g/L]. IgA returned to pre-infusion levels at 9 and 12 months after infusion, respectively[BCMA: 0.46 (0.07, 0.51) g/L vs 0.22 (0.12, 4.01) g/L; BCMA+CD19: 0.46 (0.22, 0.98) g/L vs 0.27 (0.10, 0.53) g/L]. IgM in both groups returned to pre-infusion levels 6 months after infusion[BCMA: 0.43 (0.06, 0.60) g/L vs 0.20 (0.13, 0.37) g/L; BCMA+CD19: 0.53 (0.10, 0.80) g/L vs 0.16 (0.11, 0.28) g/L]. There was no significant difference in the indexes of lymphocyte subpopulation reconstruction and immunoglobulin recovery between the two groups at each time point. Conclusion:This study showed that in patients with RRMM treated with CAR-T cells, the appropriate target antigen can be selected without considering the difference of immune reconstruction between anti-BCMA CAR-T and combined anti-CD19 CAR-T therapy.
