The bone marrow NK-cell profile predicts MRD negativity in patients with multiple myeloma treated with daratumumab-based therapy
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.
Authors
- Christie P.M. Verkleij (ORCID: https://orcid.org/0000-0002-8872-207X)
- Pieter Sonneveld (ORCID: https://orcid.org/0000-0002-0808-2237)
- Wassilis S.C. Bruins (ORCID: https://orcid.org/0000-0002-4074-9257)
- Mattia D’Agostino (ORCID: https://orcid.org/0000-0002-1711-6996)
- Inoka Twickler
- Cathelijne Fokkema (ORCID: https://orcid.org/0000-0003-0047-0590)
- Febe Smits (ORCID: https://orcid.org/0000-0002-5017-9550)
- Giada Dal Collo (ORCID: https://orcid.org/0000-0001-7348-370X)
- Sabrin Tahri (ORCID: https://orcid.org/0000-0001-8616-6607)
- Rosa Rentenaar (ORCID: https://orcid.org/0009-0008-3317-437X)
- Elodie C.G. Stoetman
- Madelon M.E. de Jong (ORCID: https://orcid.org/0000-0002-6145-6154)
- Meliha Cosovic
- Vincent H. J. van der Velden (ORCID: https://orcid.org/0000-0001-9457-3763)
- Francesca Gay (ORCID: https://orcid.org/0000-0002-8619-412X)
- Natalie Papazian (ORCID: https://orcid.org/0000-0002-8616-5652)
- Gregory van Beek (ORCID: https://orcid.org/0000-0003-0283-7069)
- Remco Hoogenboezem
- Kristine A. Frerichs (ORCID: https://orcid.org/0009-0002-6116-7843)
- Annemiek Broijl (ORCID: https://orcid.org/0000-0002-0554-8003)
- Tom Cupedo (ORCID: https://orcid.org/0000-0003-1095-4273)
- Mathijs A. Sanders (ORCID: https://orcid.org/0000-0002-8575-9213)
- Thomas Baardemans (ORCID: https://orcid.org/0009-0005-1500-6688)
- Paola M. Homan‐Weert
- Elona Saraci
- Tuna Mutis (ORCID: https://orcid.org/0000-0002-5557-7187)
- Sonja Zweegman (ORCID: https://orcid.org/0000-0002-5011-1820)
- A. Vera de Jonge (ORCID: https://orcid.org/0000-0002-5397-1762)
- Mark van Duin
- Carolien Duetz (ORCID: https://orcid.org/0000-0002-2905-0699)
- Merve Eken
- Philippe Moreau (ORCID: https://orcid.org/0000-0003-1780-8746)
- Niels W.C.J. van de Donk
- Kaz Groen
- Charlotte L.B.M. Korst
Institutions
- Dutch Cancer Society (NL)
- Hotel Dieu Hospital (CA)
- Erasmus MC (NL)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Erasmus MC Cancer Institute (NL)
- Amsterdam University Medical Centers (NL)
- Cancer Center Amsterdam (NL)
- University of Turin (IT)
- Vrije Universiteit Amsterdam (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Blood
- Published
- 2025-02-28
- DOI
- https://doi.org/10.1182/blood.2024026455
- Citations
- 11
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 19.47