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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:42

Enthalten in:

Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi - 42(2021), 9 vom: 14. Sept., Seite 733-738

Sprache:

Chinesisch

Beteiligte Personen:

Ge, J [VerfasserIn]
Zhao, T T [VerfasserIn]
Wan, C Y [VerfasserIn]
Xia, J Y [VerfasserIn]
Guo, S Y [VerfasserIn]
Yu, M X [VerfasserIn]
Chen, J [VerfasserIn]
Wang, Y [VerfasserIn]
Xu, K L [VerfasserIn]
Li, Z Y [VerfasserIn]

Links:

Volltext

Themen:

B-Cell Maturation Antigen
Chimeric antigen receptor T cells
Comparative Study
Immune reconstruction
Journal Article
Multiple myeloma
Receptors, Chimeric Antigen

Anmerkungen:

Date Completed 11.11.2021

Date Revised 31.05.2022

published: Print

Citation Status MEDLINE

doi:

10.3760/cma.j.issn.0253-2727.2021.09.004

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM332912086