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

ryanc97 said:
In some MM hospitals in China they offer NK cell infusions, but it’s not cheap, maybe more expensive than Dara and also for CD38 knockout NK cells, I think it’s a technique only for clinical trials in MM sadly.
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If CD38- nk cells does prove to be the reason for response/non response then F&M are probably well placed to evaluage whether these infusions could be viable in MECFS patients, given their expertise in oncology.
 
Then the question is how to boost cd38- NK cells. I see some literature on IL2 (Evren Alicis paper cultured NK cells in ex vivo il2 and found the cd38 expression dropped drastically in the expanded pool). They were surprised and used this cell line in MM trials.

I contacted some leading MM researchers to ask and they all laughed me out of the park lol.

TA1 boosts IL2 receptors on NK cells.

@jnmaciuch any ideas?
 
V.R.T. said:
Sorry to hear you had no response. That is quite interesting about your drastic NK cell drop maybe being to do with not having cd38- NK cells.

But perhaps people with naturally higher overall NK cells do have higher cd38- nk cells. I'm not sure we can conclude responses are likely to be low in the trial from what you've set out here.

I wonder if isatuximab will prove more or less effective than dara. Not got the spoons to read through it right now but here's something about isa mechanism of action

Isatuximab Acts Through Fc-Dependent, Independent, and Direct Pathways to Kill Multiple Myeloma Cells - PMC

Isatuximab is a monoclonal antibody targeting the transmembrane receptor and ectoenzyme CD38, a protein highly expressed on hematological malignant cells, including those in multiple myeloma (MM). Upon binding to CD38-expressing MM cells, isatuximab ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Yeah sadly, but given the late responses 4-5 months of the partial responders… maybe for some reason in men the response comes later? But then again, I don’t see any reason why gender would affect response timing.

@jnmaciuch
 
FYI @V.R.T. i have some new info that the worsening anecdote might actually be due to another drug withdrawal. As I piece it together, it makes more sense. So if true, nobody has worsened on Dara.

This aligns with the study where nobody worsened and this piecing together makes a lot more sense.
 
ryanc97 said:
FYI @V.R.T. i have some new info that the worsening anecdote might actually be due to another drug withdrawal. As I piece it together, it makes more sense. So if true, nobody has worsened on Dara.

This aligns with the study where nobody worsened and this piecing together makes a lot more sense.
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Oh right- I've heard of a worsening through someone in an LC group but it could be the same person, I didn't talk to them directly or get any details.
 
Verity said:
, I think Audrey Ryback said recently in her interview with David Tuller that the evidence they’ve collected showing two age-of-onset peaks is good evidence we’re looking at either one clinical entity or two.
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Do we have age of onset data for dara responders/non responders? Is it possible that they fall into the two age of incidence peaks?
 
ryanc97 said:
Nobody knows how these antibodies work. It’s possible immunoadsorption doesn’t get rid of them, or, they come back very fast.
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"Pro-inflammatory cytokines produced by the host, such as tumor necrosis factor alpha and interferon gamma (IFNγ), or the bacterial component lipopolysaccharide (LPS) induced the expression of CD38 in murine and human macrophages [22,27,29,30,31,32] and during maturation of dendritic cells [28,33]."

I think you're right that they come back very quickly.
 
Point is, people often point to failed IA trials and say not everyone is autoimmune. Thats the wrong way to think about it.

The IA trials are badly designed. So you have to weigh the Dara trial evidence much more than the IA trial.
 
A lot of the analysis I have seen with statistical values to try and find difference between responders and none-responders have 6 responders against the 4 non responders.

How do the numbers change though, if we assume the infamous 6th ''responder'' isn't a responder at all? But a patient who randomly fluctuated and really wanted to believe they were getting better. Thus leading to 5 responders vs. 5 none responders?

Anyone done this analysis? Sadly my brain is completely cooked and I peaked in high school when it comes to mathematics thanks to my MECFS. So I can't do it.

Given we only have n=10 I worry about the analysing of data that might be polluted by a single patient. Thus possibly leading to a wild goose chase.
 
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V.R.T. said:
Do we have age of onset data for dara responders/non responders? Is it possible that they fall into the two age of incidence peaks?
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Their paper includes a table with the mean age and ME duration:
Age (years), mean (min-max):
- All patients: 38 (20–61)
- Responders: 38 (20–61)
- Non responders: 38 (22–50)

ME/CFS disease duration (years), mean (min-max):
- All patients: 12 (3–35)
- Responders: 15 (3–35)
- Non responders: 9 (5–11)
 
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