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

Here’s how I predict things will go, they will find an effect correlated with NK cell and have about half of the non placebo responding similar to the first study.

It will reinforce all the conclusions we know about the first study and remove the placebo effect argument.

The question will still by why the NK cell correlation is so important and how do we make everyone respond. They will then focus research into that.
 
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ryanc97 said:
Here’s how I predict things will go, they will find an effect correlated with NK cell and have about half of the non placebo responding similar to the first study.

It will reinforce all the conclusions we know about the first study and remove the placebo effect argument.

The question will still by why the NK cell correlation is so important and how do we make everyone respond. They will then focus research into that.
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Surely in that scenario more than half of patients who got the drug would respond because they are only enrolling people with higher NK cell counts.

But other than that, what you've described would be pretty much the best case scenario- especially if NK cell count turned out to just correspond to drug action and raising it/waiting for it to fluctuate over the threshold was all that was required for someone to respond.

I don't know how likely it is but that's what I'm most hoping for.
 
V.R.T. said:
Surely in that scenario more than half of patients who got the drug would respond because they are only enrolling people with higher NK cell counts.

But other than that, what you've described would be pretty much the best case scenario- especially if NK cell count turned out to just correspond to drug action and raising it/waiting for it to fluctuate over the threshold was all that was required for someone to respond.

I don't know how likely it is but that's what I'm most hoping for.
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I suspect unfortunately because of repeated Covid infections a lot of peoples NK cells and functions are going to be suppressed.

I also don’t think it’s easy to raise NK cells at all. It requires either a very hard to access drug (harder to get than Dara) or self experimentation with things like peptides over a long period with repeat testing.
 
ryanc97 said:
I also don’t think it’s easy to raise NK cells at all. It requires either a very hard to access drug (harder to get than Dara)
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But isn't the anktiva guy sort of shopping it around trying to find a clinical use for it? In the scenario we're talking about this would be a good and profitable one.


ryanc97 said:
I suspect unfortunately because of repeated Covid infections a lot of peoples NK cells and functions are going to be suppressed.
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That would be really unfortunate- I don't know enough to say how likely it is though.

I think JE said a while back he thought there would be a way around the NK cell problem if the NK correlation proves to be tied to drug action.
 
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ryanc97 said:
And somehow this phenomenon only popped up in the Dara study? The ritux and cyclo studies did not show any form of synchronized response
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We don’t know if there were subtle changes in protocol to explain this—for example, ppts being advised about the potential consequences of overexertion just from participating in a trial while severe, informed by ppt experiences in previous trials. Something like that wouldn’t invalidate this trial’s results if everyone got the same spiel, but it would make a comparison to previous trials problematic.

I’d be overjoyed if the drug actually works. Just sharing a difference of opinion about how much we can or can’t conclude from those two observations
 
Jaybee00 said:
In your RA trials with ritux, of the responders, were the first patients to notice a response typically the most severe patients or the most mild? Or was there no pattern? Thanks.
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I very carefully chose 5 patients with uncontrolled disease but relatively little damage, out of 500 cases under my care. They all responded over a period of 3 months. The one with the largest extent of inflammation took longer to fully control.
 
hotblack said:
I’m still not convinced by the idea that you ‘need’ high NK cells or should be trying to boost them. It seems to make assumptions about the mechanisms at work that we do not know.
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Me neither, but its a distinct possibility imo given the NK cell separation in the pilot and the fact that daratumumab uses nk cells. Isn't NK cell count correlated with dara response in MM?

Either way we don't know anything for sure yet and there are many other possibilities.
 
V.R.T. said:
Me neither, but its a distinct possibility imo given the NK cell separation in the pilot and the fact that daratumumab uses nk cells. Isn't NK cell count correlated with dara response in MM?

Either way we don't know anything for sure yet and there are many other possibilities.
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For MM I think quality is as important as quantity from what some studies say (see this thread) although am not sure.

And on quantity, even beyond the correlation/causation point, even if we assume the number of NK cells is important for ME/CFS there seems to sometimes be assumption of how they are important and that boosting them would be beneficial.

I’m really interested in what any result here could tell us. There seem lots of possibilities and I’ve been slowly reading up and trying to learn more around CD38, NK cells, KIR and HLA. But I do not know enough to be able to say anything really. It just seems like making assumptions on mechanisms and any direction of cause and effect is a bit premature. Maybe an area we can discuss and throw some ideas around and do some wild speculation though!
 
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Jaybee00 said:
Except the Twitter guy who responded strongly to Dara had very low NK cell #.

So who knows.
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180 and long ago before his first dose. I asked him on X before.

Also he is not typical MECFS. He can lift weights now but he does not consider himself fully recovered.

Any ME patient cannot lift weights. They simply cannot.

Lifting weights is a one way ticket to hell
 
V.R.T. said:
But isn't the anktiva guy sort of shopping it around trying to find a clinical use for it? In the scenario we're talking about this would be a good and profitable one.



That would be really unfortunate- I don't know enough to say how likely it is though.

I think JE said a while back he thought there would be a way around the NK cell problem if the NK correlation proves to be tied to drug action.
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For me my NK cells went from 60 to 450 with Anktiva and after 2 Dara it went to 7.

I suspect because Anktiva boosts cd38 on NK.

In the study the high NK cell people dropped it to like 100 but not 7 like me. And mine was higher than any of them
 
ryanc97 said:
180 and long ago before his first dose. I asked him on X before.

Also he is not typical MECFS. He can lift weights now but he does not consider himself fully recovered.

Any ME patient cannot lift weights. They simply cannot.

Lifting weights is a one way ticket to hell
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I know this guy on Twitter, a Belgian ? I m pretty sure that he doesn’t have MECFS. He is not a good example.
 
ryanc97 said:
For me my NK cells went from 60 to 450 with Anktiva and after 2 Dara it went to 7.

I suspect because Anktiva boosts cd38 on NK.

In the study the high NK cell people dropped it to like 100 but not 7 like me. And mine was higher than any of them
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Did you improve with the higher NK-cell count?
 
Jonathan Edwards said:
I very carefully chose 5 patients with uncontrolled disease but relatively little damage, out of 500 cases under my care. They all responded over a period of 3 months. The one with the largest extent of inflammation took longer to fully control.
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OK thanks—and then after 3 months or so did their symptoms stabilize (flatten) or was there continued improvement in their symptoms over the following year plus as in the attached figures from the Fluge Dara paper?
 

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