TY - JOUR
T1 - The bone marrow NK-cell profile predicts MRD negativity in patients with multiple myeloma treated with daratumumab-based therapy
AU - Korst, Charlotte L. B. M.
AU - Tahri, Sabrin
AU - Duetz, Carolien
AU - Bruins, Wassilis S. C.
AU - de Jonge, A. Vera
AU - de Jong, Madelon E.
AU - Fokkema, Cathelijne
AU - Smits, Febe
AU - Groen, Kaz
AU - Verkleij, Christie P. M.
AU - Frerichs, Kristine A.
AU - Papazian, Natalie
AU - van Duin, Mark
AU - van Beek, Gregory
AU - Hoogenboezem, Remco
AU - Baardemans, Thomas
AU - Dal Collo, Giada
AU - Stoetman, Elodie C. G.
AU - Cosovic, Meliha
AU - Twickler, Inoka
AU - Rentenaar, Rosa
AU - Eken, Merve
AU - Homan-Weert, Paola M.
AU - Saraci, Elona
AU - D'Agostino, Mattia
AU - van der Velden, Vincent H. J.
AU - Sanders, Mathijs A.
AU - Gay, Francesca
AU - Broijl, Annemiek
AU - Moreau, Philippe
AU - Sonneveld, Pieter
AU - Zweegman, Sonja
AU - Mutis, Tuna
AU - Cupedo, Tom
AU - van de Donk, Niels W. C. J.
N1 - Publisher Copyright:
© 2025 American Society of Hematology
PY - 2025/6/19
Y1 - 2025/6/19
N2 - Natural killer (NK) cells are important effector cells in antibody-based immune therapies for multiple myeloma (MM) through antibody-dependent cellular cytotoxicity. Here, we used single-cell transcriptomics, flow cytometry, and functional assays to investigate the bone marrow NK-cell compartment of patients with MM at diagnosis and during treatment. We show reduced proportion of CD16+ cytotoxic NK cells in a subset of 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 measurable (or minimal) residual disease (MRD) negativity after consolidation in patients treated with daratumumab, bortezomib, thalidomide, and dexamethasone in conjunction with autologous stem cell transplantation in the CASSIOPEIA trial. In contrast, NK-cell distribution did not predict MRD negativity in patients treated in the control arm without daratumumab. These findings highlight the impact of the bone marrow NK-cell compartment on therapeutic outcomes in patients with MM receiving immunotherapy with CD38-targeting antibodies.
AB - Natural killer (NK) cells are important effector cells in antibody-based immune therapies for multiple myeloma (MM) through antibody-dependent cellular cytotoxicity. Here, we used single-cell transcriptomics, flow cytometry, and functional assays to investigate the bone marrow NK-cell compartment of patients with MM at diagnosis and during treatment. We show reduced proportion of CD16+ cytotoxic NK cells in a subset of 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 measurable (or minimal) residual disease (MRD) negativity after consolidation in patients treated with daratumumab, bortezomib, thalidomide, and dexamethasone in conjunction with autologous stem cell transplantation in the CASSIOPEIA trial. In contrast, NK-cell distribution did not predict MRD negativity in patients treated in the control arm without daratumumab. These findings highlight the impact of the bone marrow NK-cell compartment on therapeutic outcomes in patients with MM receiving immunotherapy with CD38-targeting antibodies.
UR - https://www.scopus.com/pages/publications/105001981016
U2 - 10.1182/blood.2024026455
DO - 10.1182/blood.2024026455
M3 - Article
C2 - 40019438
SN - 0006-4971
VL - 145
SP - 3007
EP - 3014
JO - Blood
JF - Blood
IS - 25
ER -