Bone marrow NK cell profile predicts MRD-negativity in multiple myeloma patients treated with daratumumab-based therapy

Single-cell transcriptomics was performed to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis (n=19) and healthy controls (n=5). We show reduced proportion of cytotoxic NK cells in a subset of MM patients at diagnosis, which correlated with decreased cytokine production and NK cell degranulation against MM cells in the presence of the anti-CD38 antibody daratumumab. In line with these findings, a low proportion of CD16+ bone marrow NK cells at diagnosis was associated with a reduced likelihood of achieving MRD-negativity post-consolidation in patients treated with daratumumab, bortezomib, thalidomide and dexamethasone in conjunction with autologous stem cell transplantation in the CASSIOPEIA trial. These findings highlight the impact of the bone marrow NK cell compartment on therapeutic outcomes in MM patients receiving immunotherapy with CD38-targeting antibodies.

本研究采用单细胞转录组测序（single-cell transcriptomics），对初诊多发性骨髓瘤（multiple myeloma, MM）患者（n=19）及健康对照者（n=5）的骨髓NK细胞（natural killer cell, NK）库展开探究。结果显示，部分初诊MM患者的细胞毒性NK细胞比例降低，该表型与达雷妥尤单抗（抗CD38抗体）存在时，患者NK细胞针对MM细胞的细胞因子产生能力下降及脱颗粒功能受损显著相关。在CASSIOPEIA试验中，接受达雷妥尤单抗、硼替佐米、沙利度胺、地塞米松联合自体干细胞移植治疗的患者亚组内，诊断时骨髓CD16阳性NK细胞比例较低者，巩固治疗后达到微小残留病（minimal residual disease, MRD）阴性的概率显著降低。上述研究结果凸显了骨髓NK细胞库对接受CD38靶向抗体免疫治疗的MM患者治疗结局的重要影响。