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

Tyler Hulett said:
So the 'worsener' / failed responder is interesting. It's this one with the bad clinical scores a year out:
View attachment 32270

This also happens to be the 'responder' with the most yellow dots - ie this person got a whole 'new set' of autoantibodies induced by the therapy. So that would totally fit with them being 'ok before' and 'not so ok after' - they don't look as bad on pre post autoab delta as they dont really have 'more autoabs' post therapy - but they have very different ones.

It looks like Dara wipe out this person's autoantibodies - and worse ones (for them at least) took their place. Immune reset doesn't mean things get better necessarily...
View attachment 32269
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I think she only relapsed after around 2 years, rigjht?
 
@ryanc97
Did you by chance also ask people for their onset? F&M will again only look at a defined onset based on their immune trigger theory.
Hopefully, Charite will include some gradual onset patients in their studies.
 
oedi said:
Yes, I had very bad reactions to each dose but it's hard to say if it was steroid induced or not. I've taken steroids before, always crashed but recovered in a week or so. After recovering from dose 1, I took dose 2 three weeks later (I was not well enough to take it 2 weeks after). I crashed again, then started to notice some energy increase for a week or so, but then really began to decline after that.

I took half the recommended steroid dose for dose 2 thinking it would be best to avoid the steroid crash, but perhaps this induced some cytokine storm which has led to my present condition.

Male, 39 y/o, sick since 2/28/24
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I am sorry this happened to you, but from my experience, as a female who also did Dara (i did 3 doses, 8 weeks now, no change right now), I think this might be from steroids, because it was for me...
For me, dara was easy peasy, it did nothing for now but 3rd dose I did without any steroids, because first 2 doses steroids K I L L E D me.
So my background, is, that from regular IVIG (1g/kg on avg per month) i recovered from walking 300-400 steps a day for over 10 years, or even less, to walking 10km a day, or 15km, and being able to travel anywhere, even alone... and then I did dara and steroids (in that condition, I obv still have many complaints so I chose to do it... ) .... and my reaction to steroids is so severe that I could walk for 4+ weeks only 100 steps a day, and had adrenal crisis, lost my period, BP 80/40, constantly feeling like i am in some dream ... It took 4 weeks to bounce back from steroids, despite my quite high baseline! after 4 weeks, I was still at 100 steps a day and NEVER leaving house. And I did only 92mg prednisone total 1st dose of Dara, and 60mg 2nd dose. It was a nightmare, for 4+ weeks I ate 600kcal a day, anorexia symptoms, 80/40 BP, weird responses to salt, so weak i walked 100 steps a day would be avg or less, ... and what is the worst part is that steroids mimic my old symptoms (pre-IVIG) like very disturbed circadian rhythm (like i am living on Mars), my body totally collapse, it mimicked MECFS....
4 weeks later, I got menstruation (3+ weeks delay from the steroids), and after that, my adrenals bounced back too.
So the horror was definitely not related to dara but to steroids, and I am wondering if something is seriously wrong with my hypothalamus to have this severe shutdown (and yeah, I remember reading there could be autoantibodies against hypothalamus?!).
These crises were nearly life-threatening for some days in those 4weeks. I also got psychiatric side effects of steroids that were also life-threatening but i think that's separate from these 'MECFS' /adrenal...ie , one can have only one

TLDR: it wasn't dara. It was steroids and I assume if my baseline wasn't so high step count, I'd crash for much longer.
 
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Pibee said:
I am sorry this happened to you, but from my experience, as a female who also did Dara (i did 3 doses, 8 weeks now, no change right now), I think this might be from steroids, because it was for me...
For me, dara was easy peasy, it did nothing for now but 3rd dose I did without any steroids, because first 2 doses steroids K I L L E D me.
So my background, is, that from regular IVIG (1g/kg on avg per month) i recovered from walking 300-400 steps a day for over 10 years, or even less, to walking 10km a day, or 15km, and being able to travel anywhere, even alone... and then I did dara and steroids (in that condition, I obv still have many complaints so I chose to do it... ) .... and my reaction to steroids is so severe that I could walk for 4+ weeks only 100 steps a day, and had adrenal crisis, lost my period, BP 80/40, constantly feeling like i am in some dream ... It took 4 weeks to bounce back from steroids, despite my quite high baseline! after 4 weeks, I was still at 100 steps a day and NEVER leaving house. And I did only 92mg prednisone total 1st dose of Dara, and 60mg 2nd dose. It was a nightmare, for 4+ weeks I ate 600kcal a day, anorexia symptoms, 80/40 BP, weird responses to salt, so weak i walked 100 steps a day would be avg or less, ... and what is the worst part is that steroids mimic my old symptoms (pre-IVIG) like very disturbed circadian rhythm (like i am living on Mars), my body totally collapse, it mimicked MECFS....
4 weeks later, I got menstruation (3+ weeks delay from the steroids), and after that, my adrenals bounced back too.
So the horror was definitely not related to dara but to steroids, and I am wondering if something is seriously wrong with my hypothalamus to have this severe shutdown (and yeah, I remember reading there could be autoantibodies against hypothalamus?!).
These crises were nearly life-threatening for some days in those 4weeks. I also got psychiatric side effects of steroids that were also life-threatening but i think that's separate from these 'MECFS' /adrenal...ie , one can have only one

TLDR: it wasn't dara. It was steroids and I assume if my baseline wasn't so high step count, I'd crash for much longer.
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That is really interesting, maybe this could be the case for others as well. You have to take quite a high dose of dexamethasone in the study. Sorry this happened to you, hope you continue to improve!
 
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Jordan09 said:
That is really interesting, maybe this could be the case for others as well. You have to take quite a high dose of dexamethasone in the study. Sorry this happened to you, hope you continue to improve!
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yeah I only took half of the dose I think, 2nd time even less, I barely tolerate any steroids, even 30mg prednisone knocked me down for 10 days
 
I'm wondering, did anybody watch Øysten Fluge's ME/CFS Research Foundation presentation on the daratumumab study this year? I had been waiting weeks for it to be uploaded, only to find out that he asked for it to be withheld. Since it's a blinded trial I'm sure he didn't share any results, but I'm wondering if there were any anecdotes, or even just a status update (how many patients have been dosed, when readout is expected, etc.).
 
smitihsj said:
I'm wondering, did anybody watch Øysten Fluge's ME/CFS Research Foundation presentation on the daratumumab study this year? I had been waiting weeks for it to be uploaded, only to find out that he asked for it to be withheld. Since it's a blinded trial I'm sure he didn't share any results, but I'm wondering if there were any anecdotes, or even just a status update (how many patients have been dosed, when readout is expected, etc.).
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There are several news articles about one of the patients from the pilot (e.g. this), but they have explicitly asked the participants in ResetME to not discuss their participation, symptoms etc. so I doubt they told any anecdotes from that.

The latest status reports can be found in the ResetME thread.

They’ve said 2029 before, but napkin math says that the last participants might be through the follow-up at the end of 2027 or early 2028. So anything after that really, allowing for some time to do the analyses and write the reports.
 
They will unblind in summer 2028.

66 patients will receive treatment with Daratumumab/placebo in the study and 5 with severe ME with Daratumumab. After a secret and hidden lottery, 44 ME patients will receive treatment with Daratumumab and 22 ME patients with placebo. 5 patients with severe ME will receive Daratumumab. Neither the researchers nor the patients will know who is receiving treatment and who is receiving placebo until 72 weeks after the last treatment round – the protocol will open in the summer of 2028.
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www.me-foreningen.no

Innsamling til ResetME

Det finnes fortsatt ingen godkjent, effektiv behandling for ME, men du kan hjelpe oss med å endre det! Doner til ResetME studien på Haukeland.
www.me-foreningen.no www.me-foreningen.no
 
OrganicChilli said:
They will unblind in summer 2028.



www.me-foreningen.no

Innsamling til ResetME

Det finnes fortsatt ingen godkjent, effektiv behandling for ME, men du kan hjelpe oss med å endre det! Doner til ResetME studien på Haukeland.
www.me-foreningen.no www.me-foreningen.no
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That presumably means that the analyses will be completed by the summer of 2028. I don’t know how long it would take to write a paper, but it can’t be that long. The publication process might take some time if they don’t go for a preprint first.
 
Utsikt said:
That presumably means that the analyses will be completed by the summer of 2028. I don’t know how long it would take to write a paper, but it can’t be that long. The publication process might take some time if they don’t go for a preprint first.
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I hope you're right. I specifically asked AI if the translation was correct and it insisted "the protocol will open" means unblinding. Which is quite annoying because if the last patient receives daratumumab this summer and they wait 70ish weeks, we end up in Dec 27/Jan 28 and should have an analysis by summer 28.
 
OrganicChilli said:
I hope you're right. I specifically asked AI if the translation was correct and it insisted "the protocol will open" means unblinding. Which is quite annoying because if the last patient receives daratumumab this summer and they wait 70ish weeks, we end up in Dec 27/Jan 28 and should have an analysis by summer 28.
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I can confirm the translation is correct.

The unblinding will happen at the end of the analysis. If you have seen the video from the last ritux trial when they unblinded the data, they knew right away that the trial had a null result because the analysis was already done.

They would also be able to write the introduction and the methodology before that, and a rough outline of the results section that’s given from the predefined outcomes. Assuming they have the time of course.
 
Utsikt said:
The unblinding will happen at the end of the analysis. If you have seen the video from the last ritux trial when they unblinded the data, they knew right away that the trial had a null result because the analysis was already done.
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I don't understand. Maybe I don't understand what unblinding means in this context.

How can you analyse the data if it's all blinded, i.e. you don't know which data points come from the treatment and which from placebo?
 
Felis Catus said:
I don't understand. Maybe I don't understand what unblinding means in this context.

How can you analyse the data if it's all blinded, i.e. you don't know which data points come from the treatment and which from placebo?
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You know it’s from group A or group B, and at the end they get to know which group is which.

I also don’t think it’s uncommon that the analysis is done by someone not involved in the day to day of the project, otherwise the researchers would know early on if the trial is positive because it would be obvious from just reading the data.
 
Felis Catus said:
How can you analyse the data if it's all blinded, i.e. you don't know which data points come from the treatment and which from placebo?
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I can see you puzzlement but I think it makes sense. You can input all the observational data into a computer that also has access to the blinding code. (And the 'computer' can be what Alan Turing originally meant by the word - a man that computes. As long as you enter all the observational data before asking the computer what the result is it/they can do the analysis and have it ready.
 
Jonathan Edwards said:
I can see you puzzlement but I think it makes sense. You can input all the observational data into a computer that also has access to the blinding code. (And the 'computer' can be what Alan Turing originally meant by the word - a man that computes. As long as you enter all the observational data before asking the computer what the result is it/they can do the analysis and have it ready.
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Yes, I was actually thinking how assignment could be stored in a human non-readable format, and you could have a piece of code that accesses the assignment without revealing it to the person doing the analyses.

But I was also thinking that as soon as you start plotting the data (or their transformations), you've basically unblinded it?
 
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