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

V.R.T. said:
That's concerning. Fluge said the worsener was severe not moderate in the presentation and chalked it up to the exertion of the visits. Moderate makes that much less likely.
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Well i dont have every detail but she had spoken about it to fellow ME patients, and was mostly housebound but out of the house weekly before this. Got very sick with new gastro issues etc, and also a face rash, only had one dose. Needed full time care for 10 weeks. Not her normal ME symptoms so dont know why they are saying that. Seems like she is ok now, but i hope people dont try this outside the trial
 
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Jordan09 said:
Well i dont have every detail but she had spoke about it to fellow ME patients, and was mostly housebound but out of the house weekly before this. Got very sick with new gastro issues etc, and also a face rash, only had one dose. Needed full time care for 10 weeks. Not her normal ME symptoms so dont know why they are saying that. Seems like she is ok now, but i hope people dont try this outside the trial
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That sounds nasty. Glad she's better now.
 
Jordan09 said:
It is true, she posted it on social media. Not recognised as an SEA but could be drug induced alopecia, or just random, she could have had placebo. But happened right after she started the trial
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Hair loss is one of the classic 'side effects' that occurs pretty much the same in placebo as test treatment. There may be some rare cases of drug induced alopecia but a post on social media is not the leve of evidence we need to guide discussion.
 
Jonathan Edwards said:
Hair loss is one of the classic 'side effects' that occurs pretty much the same in placebo as test treatment. There may be some rare cases of drug induced alopecia but a post on social media is not the leve of evidence we need to guide discussion.
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I agree, let me know if you want me to delete the comment. But a bald head and eyebrows, is that really a normal placebo side effect? Just genuinely curious
 
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ryanc97 said:
Internal tremors are very much commonly discussed in benzo communities, but also there are many stories in the ME CFS subreddit. So I’m not ruling it out. However…

At the same time, many ME CFS are using long term psych drugs, SSRI, SNRI, benzos….. which also is connected to internal tremors which confounds things..
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I sometimes get internal tremors in the wee hours of the morning - around 3-5am - that wake me up. I've never taken a benzo or SSRI, SNRI, steroid or any psych drug in my life.
 
oedi said:
The benzo usage is completely irrelevant like I've communicated to you multiple times. I had been on a consistent and unchanged dose for 9 months. The tremors started after dara dose 2 with no change in benzo dosage. I then experimented with dosing in multiple ways, initially increasing due to the immediate worsening, without any discernable change in the tremors. I even went cold turkey for 2 weeks and am back on my initial dose without any change. Tremors only seem to increase with exertion and wan with radical rest.

I've told you this more than once and you failed to correctly report that to this forum in favor of your own perception.

As for the steroids, it is of course possible but I've endured many steroid crashes, at equivalent doses, in the past without permanent worsening. My Pemgarda infusions with steroids are one example. And then there is the unique burning reaction I experienced after dose 2. The most likely explanation is dara made me permanently worse. I'll let the people here judge for themselves
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Thank you spending your energy to inform us of your experience.
 
Jordan09 said:
I hope there will be some answers from the trial. Maybe more of at temporary immune flare? And why are some getting better but others much worse, we will have to wait and see
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It's a shame to think that some will get worse. There is someone on twitter who talks about checking genes that are involved in autoimmune diseases before giving them something that could cause such severe problems.
 
Maybe someone who understands how dara works better than me can weigh in on this. I was just thinking about the report of worsening from the trial.

Daratumumab is known to cause fatigue as a side effect even in people without ME, sometimes for months. Personally if something other than ME causes fatigue for me, it appears to worsen my ME because the extra burden of fatigue makes it harder to function overall, but it doesn’t necessarily change my long-term baseline. Is it possible this person who worsened for ten weeks did not really experience a fundamental change in whatever ME is but simply felt much worse due to the fatigue side effect? Does this question even make sense?

Dara stays in your system much longer than ten weeks, and it also causes major immune changes for much longer than that timeline. It seems to me if dara fundamentally worsens whatever ME is, that should not clear up in 10 weeks. But a drug side effect of severe fatigue that is not caused by the same mechanism as ME could match that timeline well.
 
Verity said:
Maybe someone who understands how dara works better than me can weigh in on this. I was just thinking about the report of worsening from the trial.

Daratumumab is known to cause fatigue as a side effect even in people without ME, sometimes for months. Personally if something other than ME causes fatigue for me, it appears to worsen my ME because the extra burden of fatigue makes it harder to function overall, but it doesn’t necessarily change my long-term baseline. Is it possible this person who worsened for ten weeks did not really experience a fundamental change in whatever ME is but simply felt much worse due to the fatigue side effect? Does this question even make sense?

Dara stays in your system much longer than ten weeks, and it also causes major immune changes for much longer than that timeline. It seems to me if dara fundamentally worsens whatever ME is, that should not clear up in 10 weeks. But a drug side effect of severe fatigue that is not caused by the same mechanism as ME could match that timeline well.
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That sounds like a possible explanation, darzalex side effects can apparently last 8-12 weeks so that will fit the timeline. There are some cancer patients that just cant tolerate immunotherapy due to side effects, so maybe the same goes for ME
 
Verity said:
Maybe someone who understands how dara works better than me can weigh in on this. I was just thinking about the report of worsening from the trial.

Daratumumab is known to cause fatigue as a side effect even in people without ME, sometimes for months. Personally if something other than ME causes fatigue for me, it appears to worsen my ME because the extra burden of fatigue makes it harder to function overall, but it doesn’t necessarily change my long-term baseline. Is it possible this person who worsened for ten weeks did not really experience a fundamental change in whatever ME is but simply felt much worse due to the fatigue side effect? Does this question even make sense?

Dara stays in your system much longer than ten weeks, and it also causes major immune changes for much longer than that timeline. It seems to me if dara fundamentally worsens whatever ME is, that should not clear up in 10 weeks. But a drug side effect of severe fatigue that is not caused by the same mechanism as ME could match that timeline well.
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5 half lives of dara is about 100 days, which is generally considered the clearance timeframe. But immune reconstitution does take longer. From my research, 6mo for nk cells and only 13mg/dl a month for IgG. It could take 3 years to replenish IgG. I'm considering Hizentra at the moment.
 
If Dara really caused worsening then it is likely because it got rid of good LLPC but not bad, reducing the natural IGG FCRN ability. Then IVIG or SCIG will help symptoms.

Dara did not cause you to worsen because it suppressed your immune system against latent viruses.
 
So the 'worsener' / failed responder is interesting. It's this one with the bad clinical scores a year out:
1778471951908.png

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...
1778471827588.png
 
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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The worsener i talked about, just had the treatment in the new phase 2 study. There will be no data on her because she withdraw from the trial. But maybe the same happened there, will be very interesting to get the full results in a couple of years
 
Jordan09 said:
The worsener i talked about, just had the treatment in the new phase 2 study. There will be no data on her because she withdraw from the trial. But maybe the same happened there, will be very interesting to get the full results in a couple of years
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Wait.

Are you referring to the worsener in P1 or worsener in P2? There are two worseners:

Patient 05 in green line in P1.

The unknown worsener who got bedbound from Dara in P2. But you said she recovered right to baseline? Then she withdrew from the trial?
 
ryanc97 said:
Wait.

Are you referring to the worsener in P1 or worsener in P2? There are two worseners:

Patient 05 in green line in P1.

The unknown worsener who got bedbound from Dara in P2. But you said she recovered right to baseline? Then she withdrew from the trial?
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Oh sorry, yes i am referring to the person in P2. I was told she eventually recovered to baseline, but there were no tests or anything done when she withdrew, so there will be no data on her
 
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Jordan09 said:
The worsener i talked about, just had the treatment in the new phase 2 study. There will be no data on her because she withdraw from the trial. But maybe the same happened there, will be very interesting to get the full results in a couple of years
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My apologies didn't know that - do know that Bergen folks don't consider that person a 'real responder' as it didn't stay - could be that they never really had a proper response too
 
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