sBCMA Plasma Level Dynamics and Anti-BCMA CAR-T-Cell Treatment in Relapsed Multiple Myeloma

被引:18
|
作者
Seipel, Katja [1 ]
Porret, Naomi [2 ]
Wiedemann, Gertrud [2 ]
Jeker, Barbara [3 ]
Bacher, Vera Ulrike [2 ]
Pabst, Thomas [3 ]
机构
[1] Univ Bern, Dept Biomed Res, CH-2008 Bern, Switzerland
[2] Univ Bern, Bern Univ Hosp, Dept Hematol & Cent Hematol Lab, Inselspital, CH-3010 Bern, Switzerland
[3] Bern Univ Hosp, Dept Med Oncol, CH-3010 Bern, Switzerland
基金
瑞士国家科学基金会;
关键词
B-cell maturation antigen (BCMA); soluble BCMA (sBCMA); multiple myeloma (MM); anti-BCMA CAR-T cell therapy; MATURATION ANTIGEN; RECEPTORS; BIOMARKER; CRITERIA; THERAPY;
D O I
10.3390/cimb44040098
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
BACKGROUND: Novel chimeric antigen receptor T-cells (CAR-T) target the B-cell maturation antigen (BCMA) expressed on multiple myeloma cells. Assays monitoring CAR-T cell expansion and treatment response are being implemented in clinical routine. METHODS: Plasma levels of soluble BCMA (sBCMA) and anti-BCMA CAR-T cell copy numbers were monitored in the blood, following CAR-T cell infusion in patients with relapsed multiple myeloma. sBCMA peptide concentration was determined in the plasma, applying a human BCMA/TNFRS17 ELISA. ddPCR was performed using probes targeting the intracellular signaling domains 4-1BB und CD3zeta of the anti-BCMA CAR-T construct. RESULTS: We report responses in the first five patients who received anti-BCMA CAR- T cell therapy at our center. Four patients achieved a complete remission (CR) in the bone marrow one month after CAR-T infusion, with three patients achieving stringent CR, determined by flow cytometry techniques. Anti-BCMA CAR-T cells were detectable in the peripheral blood for up to 300 days, with copy numbers peaking 7 to 14 days post-infusion. sBCMA plasma levels started declining one to ten days post infusion, reaching minimal levels 30 to 60 days post infusion, before rebounding to normal levels. CONCLUSIONS: Our data confirm a favorable response to treatment in four of the first five patients receiving anti-BCMA CAR-T at our hospital. Anti-BCMA CAR-T cell expansion seems to peak in the peripheral blood in a similar pattern compared to the CAR-T cell products already approved for lymphoma treatment. sBCMA plasma level may be a valid biomarker in assessing response to BCMA-targeting therapies in myeloma patients.
引用
收藏
页码:1463 / 1471
页数:9
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