Department of Hematology, Oncology and Rheumatology, Heidelberg University, Heidelberg, Germany.
Amyloidosis Center, Heidelberg University, Heidelberg, Germany.
Cytometry B Clin Cytom. 2018 Sep;94(5):611-620. doi: 10.1002/cyto.b.21636. Epub 2018 Apr 20.
Recent approaches in multiple myeloma (MM) treatment have targeted CD38. As antigen expression levels on plasma cells (PCs) were demonstrated to affect response to monoclonal antibody (mAb) treatment, a precise characterization of PC phenotype is warranted.
Anti-CD38 mAb (isatuximab) was tested for antibody-dependent cellular cytotoxicity (ADCC) in MM cell lines. Quantification of the number of sites (NOS) of CD38 on bone marrow PCs and other immune cells obtained from light chain (AL) amyloidosis (n = 46) and smoldering multiple myeloma (SMM) patients (n = 19) was performed with two different quantitative flow cytometry (QFCM) applications.
ADCC activity of isatuximab was observed in cell lines with >100 × 10 CD38-NOS only. The average PC CD38-NOS was 153 ± 53 × 10 in AL amyloidosis and 138.7 ± 53 × 10 in SMM patients. Eight (17%) AL amyloidosis and 4 (21%) SMM patients showed a PC CD38-NOS level <100 × 10 . In four AL amyloidosis and two SMM patients <10% of PCs had a CD38-NOS ≥100 × 10 . The CD38-NOS identified on bone marrow lymphocytes, monocytes, and granulocytes was two log units below the CD38-NOS on PCs (P < 0.001). No significant differences in CD38-NOS expression levels on any of the analyzed PC subpopulations in AL amyloidosis and SMM patients were identified.
Levels of CD38 expression affect the isatuximab-mediated ADCC in vitro. As PCs of patients with AL amyloidosis and SMM do not homogenously express high CD38 our data provide a rationale for assessment of CD38-NOS in patients with PC disorders prior to anti-CD38 treatment. © 2018 International Clinical Cytometry Society.
多发性骨髓瘤（MM）治疗的最新方法针对 CD38。由于浆细胞（PC）上的抗原表达水平被证明会影响单克隆抗体（mAb）治疗的反应，因此需要对 PC 表型进行精确表征。
在 MM 细胞系中测试抗 CD38 mAb（依沙妥昔单抗）的抗体依赖性细胞毒性（ADCC）。使用两种不同的定量流式细胞术（QFCM）应用程序，对来自轻链（AL）淀粉样变性（n = 46）和冒烟型多发性骨髓瘤（SMM）患者（n = 19）的骨髓 PCs 和其他免疫细胞中的 CD38 位点（NOS）数量进行定量。
仅在 >100 × 10 CD38-NOS 的细胞系中观察到依沙妥昔单抗的 ADCC 活性。AL 淀粉样变性患者的平均 PC CD38-NOS 为 153 ± 53 × 10，SMM 患者为 138.7 ± 53 × 10。8 例（17%）AL 淀粉样变性和 4 例（21%）SMM 患者的 PC CD38-NOS 水平 <100 × 10。在 4 例 AL 淀粉样变性和 2 例 SMM 患者中，<10%的 PCs 的 CD38-NOS ≥100 × 10。骨髓淋巴细胞、单核细胞和粒细胞上检测到的 CD38-NOS 比 PCs 上的 CD38-NOS 低两个对数级（P < 0.001）。在 AL 淀粉样变性和 SMM 患者中，任何分析的 PC 亚群上的 CD38-NOS 表达水平均无显著差异。
CD38 表达水平会影响依沙妥昔单抗介导的体外 ADCC。由于 AL 淀粉样变性和 SMM 患者的 PCs 并不均匀表达高水平的 CD38，因此我们的数据为在接受抗 CD38 治疗之前对 PC 疾病患者的 CD38-NOS 进行评估提供了依据。
