The bone marrow NK-cell profile predicts MRD negativity in patients with multiple myeloma treated with daratumumab-based therapy, Korst et al. 2025

[Jaybee00]

Key Points​

• A reduced proportion of CD16+ bone marrow NK cells at diagnosis was associated with decreased daratumumab-mediated NK-cell degranulation.
• Reduced BM CD16+ NK-cell proportion was associated with reduced likelihood of achieving MRD negativity upon daratumumab-based therapy.

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.

https://ashpublications.org/blood/article/145/25/3007/535791/The-bone-marrow-NK-cell-profile-predicts-MRD

Commentary

A natural head start to MRD negativity in multiple myeloma​

https://ashpublications.org/blood/article/145/25/2936/537727/A-natural-head-start-to-MRD-negativity-in-multiple

 

[forestglip]

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.

Nice find. From daratumumab for ME/CFS:

Plasma cell targeting with the anti-CD38 antibody daratumumab in ME/CFS -a clinical pilot study, 2025, Fluge et al

Low baseline NK-cell count in blood was associated with lack of clinical response.

Plot of baseline NK count vs improvement from video posted here.

 

[Turtle]

That could mean even if there is treatment available it won't be successful in me, because of very low NK-cells

 

[V.R.T.]

That could mean even if there is treatment available it won't be successful in me, because of very low NK-cells

Perhaps that is true if Daratumumab works but it may well point the way to other treatments with a different mechanism that are more universally effective.

 

[forestglip]

Similarly:

NK Cell Phenotype Is Associated With Response and Resistance to Daratumumab in Relapsed/Refractory Multiple Myeloma (2023, HemaSphere)

Natural killer (NK) cells play an important role during daratumumab therapy by mediating antibody-dependent cellular cytotoxicity via their FcγRIII receptor (CD16), but they are also rapidly decreased following initiation of daratumumab treatment.

At baseline, nonresponding patients had a significantly lower proportion of CD16+ and granzyme B+ NK cells, and higher frequency of TIM-3+ and HLA-DR+ NK cells, consistent with a more activated/exhausted phenotype. These NK cell characteristics were also predictive of inferior progression-free survival and overall survival. Upon initiation of daratumumab treatment, NK cells were rapidly depleted. Persisting NK cells exhibited an activated and exhausted phenotype with reduced expression of CD16 and granzyme B, and increased expression of TIM-3 and HLA-DR.

We observed that addition of healthy donor-derived purified NK cells to BM samples from patients with either primary or acquired daratumumab-resistance improved daratumumab-mediated MM cell killing.

 

[Turtle]

Perhaps that is true if Daratumumab works but it may well point the way to other treatments with a different mechanism that are more universally effective.

Maybe in how many years?
It would also block monoclonal antibody treatment JE wrote about.
I was once offered a DNA-test because there was a suspicion of a monoclonal T-cell population, the lab did not have enough blood tot test right away. Blood draws are often problematic. I asked my GP if the lab did find something could it be treated. He answered : No.
So I declined testing: why bother.
Maybe I would have taken that test now, having a little more knowlegde.

 

[V.R.T.]

Maybe in how many years?
It would also block monoclonal antibody treatment JE wrote about.

'In how many years' is the pressing question about all this no one can answer it seems .

Would it also block the monoclonals? Damn I didn't realise that.