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）与健康对照者（n=5）的骨髓NK细胞组分展开探究。研究发现，部分初诊MM患者的细胞毒性NK细胞比例降低，且该现象与抗CD38抗体达雷妥尤单抗（daratumumab）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。结合上述结果，在CASSIOPEIA临床试验中，接受达雷妥尤单抗、硼替佐米、沙利度胺、地塞米松联合自体造血干细胞移植治疗的患者中，初诊时CD16阳性骨髓NK细胞比例较低者，其巩固治疗后达到微小残留病（minimal residual disease, MRD）阴性状态的概率显著降低。本研究结果揭示了骨髓NK细胞组分对接受CD38靶向抗体免疫治疗的MM患者治疗结局的影响。