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

PageofME said:
I watched the Norwegian documentary about Fluge's work. This is exactly what he's doing in my view.
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Well, you have yourself admitted that you are unfamiliar with immunology. I know Oystein and Olav and I can assure you that there was nothing random about their choices. It has all been very logically argued. They may be off track but they do have a rationale. What is the rationale for 'randomly' picking HHV6?!!
 
What worries me about the idea of HHV6 is that it was originally proposed on the basis that there might be immunodeficiency in ME/CFS but that has not been confirmed (if there was we would expect other opportunistic problems and those are not reported). If there is no immunocompromise then the symptoms of ME/CFS do not seem to fit with recognised accounts of HHV6 infection in adults.
 
PageofME said:
But I am.

I watched the Norwegian documentary about Fluge's work. This is exactly what he's doing in my view.
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Okay then you have seriously misunderstood. F&M observed massive improvements in cancer patients with ME/CFS following treatment for cancer. So significant they were asking for more chemotherapy. They have followed this clinical observation through several drug trials, including a positive phase 2 of cyclophosphamine, and are now using daratumumab in order to try and get that effect in a safer drug.

There is also evidence from a study that ME/CFS B cells express more CD38 when stimulated than the B cells of healthy controls. Daratumumab is an anti CD38 drug. That is not in any way trying random drugs in an attempt to find a miracle cure. It is following the clinical and scientific evidence where it leads you.
 
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V.R.T. said:
Okay then you have seriously misunderstood. F&M observed massive improvements in cancer patients with ME/CFS following treatment for cancer. So significant they were asking for more chemotherapy. They have followed this clinical observation through several drug trials, including a positive phase 2 of cyclophosphamine, and are now using daratumumab in order to try and get that effect in a safer drug.

There is also evidence from a study that ME/CFS B cells express more CD38 that stimulated than other cells. Daratumumab is an anti CD38 drug. That is not in any way trying random drugs in an attempt to find a miracle cure. It is following the clinical and scientific evidence where it leads you.
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I think there is a case for saying that F&M might be making a few leaps of faith, and that we’re cutting them a bit of slack because they have demonstrated that 1) they are very good at doing trials, 2) they are willing to accept negative data, and 3) we want treatments as soon as possible.

I trust @Jonathan Edwards if he says that their rationale is well reasoned, and that that might mean that they have crossed the threshold of where it might be warranted to do treatment trials even if they are based on some unverified assumptions.

From a layperson perspective, one of the main differences between F&M and the other treatment researchers is that F&M’s ideas can’t be easily picked apart with existing negative findings. Most proposed treatments seem like they are based on memes or hype about what someone thinks is wrong, regardless of what the data says.
 
The problem with all these viral reactivation tests is that there is no healthy controls done to interpret them against because no HC people get these tests.

So ME people panic and start taking all kinds of tests in a bid to find something wrong and once you see the high viral scores (which we have no HC population to compare to) they zoom in on that and assume it is a “latent virus” causing their symptoms. Then they start loading on antivirals for the cure.


I’ve been there and done that.
 
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ryanc97 said:
The problem with all these viral reactivation tests is that there is no healthy controls done to interpret them against because no HC people get these tests.

So ME people panic and start taking all kinds of tests in a bid to find something wrong and once you see the high viral scores (which we have no HC population to compare to) they zoom in on that and assume it is a “latent virus” causing their symptoms. Then they start loading on antivirals for the cure.


I’ve been there and done that.
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Expect that there have been several large scale studies looking at different viruses in ME/CFS and HC and finding largely no differences. So any explanation will have to be different to the standard explanation seen online.
 
EndME said:
Expect that there have been several large scale studies looking at different viruses in ME/CFS and HC and finding largely no differences. So any explanation will have to be different to the standard explanation seen online.
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Yes which proves my point. People get fooled by these tests because they don’t compare their results to a healthy population
 
Does anyone know if doing IVIG too close say the day before a MAB like Dara, in theory, would reduce the potency of it? Something to do with FCRN and the recycling of antibodies, which Dara is also an antibody.

@Jonathan Edwards

I asked ChatGPT and it said 70g of IVIG a day before 1800mg Dara would reduce the potency by 30%. I do not have enough biological knowledge to comment so I would like to ask the experts.

Scholars@Duke publication: The potential impact of timing of IVIG administration on the efficacy of rituximab for immune tolerance induction for patients with Pompe disease.

Scholars@Duke
scholars.duke.edu

However, in our infantile Pompe disease patients that received the ITI protocol (rituximab24–48 h prior to IVIG), we observed B-cell recovery within severalweeks (range 11–55 weeks post-rituximab) in some cases, indicatingthere could be altered pharmacokinetics (PK) and pharmacodynamics(PD) of rituximab. Thus, although IVIG administration may be vital inpreventing infection, the timing of rituximab and IVIG administrationmay be important to the optimal outcome of tolerance induction by thistherapeutic cocktail of rituximab, methotrexate, and IVIG.


The protocol was 500mg/kg so at a 70kg person tahts 30g. So it seems like it does sharply reduce potency of the rituximab given the B cells come back in a month instead of 6 months. Question is does it extrapolate to Dara
 
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ryanc97 said:
I asked ChatGPT and it said 70g of IVIG a day before 1800mg Dara would reduce the potency by 30%. I do not have enough biological knowledge to comment so I would like to ask the experts.
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The paper quoted looks to me to be based on a misunderstanding of Ig half life. I am also amazed that anyone should consider giving IVIG with rituximab (what the paper discusses). I would ignore it.

70g is a lot of Ig but a normal person probably already has 50-100gm in body fluids. It all sounds very speculative and irrelevant to me but I can't see a good reason to be having IVIG anyway?
 
Jonathan Edwards said:
The paper quoted looks to me to be based on a misunderstanding of Ig half life. I am also amazed that anyone should consider giving IVIG with rituximab (what the paper discusses). I would ignore it.

70g is a lot of Ig but a normal person probably already has 50-100gm in body fluids. It all sounds very speculative and irrelevant to me but I can't see a good reason to be having IVIG anyway?
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Well because in theory Dara depletes IGG and makes you more susceptible to infection so IVIG could help with that while you are immuno suppressed while on Dara.

Why do you say that IVIG with Ritux is a bad idea anyway? Aside from the effect of making it less potent.
 
ryanc97 said:
Well because in theory Dara depletes IGG and makes you more susceptible to infection so IVIG could help with that while you are immuno suppressed while on Dara.
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Yes, but then you would want to give the IVIG much later when the levels have gone down, not when the levels are up.

Same for ritux. We gave IVIG 3 months later if needed. But not if not needed. Giving the IVIG at the same time seems to me barmy.
 
Jonathan Edwards said:
The paper quoted looks to me to be based on a misunderstanding of Ig half life. I am also amazed that anyone should consider giving IVIG with rituximab (what the paper discusses). I would ignore it.

70g is a lot of Ig but a normal person probably already has 50-100gm in body fluids. It all sounds very speculative and irrelevant to me but I can't see a good reason to be having IVIG anyway?
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IVIG is useless for severe MECFS ? I can have IVIG for free in public hospital. I have POTS too... i dont know if i have to take the risk. I dont find papers mentionned IVIG for trial in MECF.
 
Jonathan Edwards said:
Yes, but then you would want to give the IVIG much later when the levels have gone down, not when the levels are up.

Same for ritux. We gave IVIG 3 months later if needed. But not if not needed. Giving the IVIG at the same time seems to me barmy.
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Barmy because it decreases potency of the mab?
 
ryanc97 said:
Barmy because it decreases potency of the mab?
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No, because it is being given at a time when it is not needed and since it has a short half life it involves pouring money down the drain and exposing the patient to unnecessary risks of unwanted effects. Unless I have misunderstood it sounds to me as if there is some seriously incompetent therapeutics going on.
 
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