The bone marrow NK-cell profile predicts MRD negativity in patients with multiple myeloma treated with daratumumab-based therapy
Abstract
Abstract 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.
Article Details
Authors (35)
Charlotte L. B. M. Korst
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Sabrin Tahri
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Carolien Duetz
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Wassilis S. C. Bruins
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
A. Vera de Jonge
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Madelon E. de Jong
3Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Cathelijne Fokkema
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Febe Smits
6Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Kaz Groen
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Christie P. M. Verkleij
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Kristine A. Frerichs
1Department of Hematology, Amsterdam Universitair Medische Centra, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Natalie Papazian
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Mark van Duin
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Gregory van Beek
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Remco Hoogenboezem
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Thomas Baardemans
1Department of Hematology, Amsterdam Universitair Medische Centra, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Giada Dal Collo
1Department of Hematology, Amsterdam Universitair Medische Centra, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Elodie C. G. Stoetman
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Meliha Cosovic
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Inoka Twickler
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Rosa Rentenaar
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Merve Eken
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Paola M. Homan-Weert
1Department of Hematology, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Elona Saraci
4Division of Hematology 1, Azienda Ospedaliero-Universitaria Citta della salute e della Scienza, Department of Molecular Biotechnology and Health Science, University of Torino, Turin, Italy
Mattia D’Agostino
4Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy
Vincent H. J. van der Velden
2Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
Mathijs A. Sanders
Cancer, Ageing and Somatic Mutation, Wellcome Sanger Institute
Francesca Gay
Annemiek Broijl
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
Philippe Moreau
Pieter Sonneveld
Sonja Zweegman
Tuna Mutis
6Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Tom Cupedo
Erasmus MC Cancer Institute
Niels W. C. J. van de Donk