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.