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

Maybe there’s some kind of CD38 targeting CAR-NK or CAR-T cell therapy that can better target and deplete CD38 plasmablasts while sparing CD38high NK cells and retaining sufficient ADCC cytotoxicity. Would really help test their theory and see if better responses can be produced in the lower NK baseline non-responders.

That’s the problem with monoclonals like dara and ritux they don’t effectively deplete all their target in a subset of patients (in cancer and autoimmune diseases too) leading to inadequate clinical responses and researchers questioning their pathomechanism theories when in reality it’s just the drug isn’t good enough.
 
V.R.T. said:
I hadn't heard about this! Was this Fluge and Mella too?
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In a new amendment to the present study, we aim to test this by including four new patients with ME/CFS following a SARS-CoV2 infection who fulfil the trial inclusion criteria, and who have baseline NK-cell numbers above 125 (x106/L). In this amendment, the daratumumab dosing schedule has been reduced. These data will be published later as a case series. Possible interventions for antibody-targeting therapies in Long COVID have recently been summarized (60).
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In general I like the idea of using steps as an activity metric.

I think steps is a fine metric for somewhere like Bergen where it never gets very hot and it never gets very cold.

What if you did the study in Riyadh or Dubai or Miami or Phoenix where it really gets too hot in the summer to walk around a lot? Similarly what if you did it in Winnipeg or Minneapolis or Fairbanks, where it gets too cold in the winter to walk around outside in comfort?

Weather could end up being a confounding variable for steps in certain areas I think.
 
Jaybee00 said:
In general I like the idea of using steps as an activity metric.
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I find there is too much variation day to day, and somewhat week to week, and month to month, but monthly tracking seems to work well when compared to the previous year (I have seasonal variation). So long term follow-up is really important for treatment studies with minor or moderate effect. The only downside to tracking activity is a change of recording device seems cause a a big jump - I've seen 10-20% difference.

Saying that, the step level of activity change being displayed with Dara is a huge step change and that can certainly be tracked weekly or monthly within the same year to show the effect.
 
Jaybee00 said:
In general I like the idea of using steps as an activity metric.

I think steps is a fine metric for somewhere like Bergen where it never gets very hot and it never gets very cold.
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For context: The weather in Bergen is atrocious - the city is by the coast and surrounded by seven mountains so it rains a lot. Like ~2/3 of the year has rainy days.

But the temperatures are usually in the range of 25 to -10 C throughout the year.
 
wigglethemouse said:
I find there is too much variation day to day, and somewhat week to week, and month to month, but monthly tracking seems to work well when compared to the previous year (I have seasonal variation). So long term follow-up is really important for treatment studies with minor or moderate effect. The only downside to tracking activity is a change of recording device seems cause a a big jump - I've seen 10-20% difference.
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It would help if it had some context too.

It's probably natural for most people to increase their steps if their capacity's better, but what if instead of going out for walks and visits someone was aching to pick up their studies again? Their steps could decrease by 50%; from that measure alone it'd look as if the treatment made them worse, when actually they improved by half.
 
Kitty said:
It would help if it had some context too.

It's probably natural for most people to increase their steps if their capacity's better, but what if instead of going out for walks and visits someone was aching to pick up their studies again? Their steps could decrease by 50%; from that measure alone it'd look as if the treatment made them worse, when actually they improved by half.
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Most people with ME doesn’t move that much. On average patients would move more if they are significantly better. Perhaps one person won’t, but on average you would see people moving more.
Not particularly relevant, but I go much worse, then improved some and went back to uni. Average steps doubled even though I drove a car to uni. I walked around to lectures, to have lunch, study groups and more.
 
Utsikt said:
For context: The weather in Bergen is atrocious - the city is by the coast and surrounded by seven mountains so it rains a lot. Like ~2/3 of the year has rainy days.
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I stand corrected! But I think Norwegians don’t mind the rainy-ish weather. I remember hiking somewhere in Norway on a drizzly day and the trail was packed.

Please correct me again if this is a malicious or false stereotype!
 
Jaybee00 said:
I stand corrected! But I think Norwegians don’t mind the rainy-ish weather. I remember hiking somewhere in Norway on a drizzly day and the trail was packed.

Correct me again if this is a malicious or false stereotype!
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We usually say «there is no bad weather, only bad clothes» (it rhymes in Norwegian).

And people from Bergen are proud of their weather. But they are proud in general, there’s a running joke that they want to become independent.

But the gist of it is that Norwegian go outside whenever, but they love the sun (the concept «Utepils» (outside beer) is explained here).
 
Seems like high IGG4 is important. Can anyone translate this paragraph into normal English?

The IgG subclasses, measured at baseline and at 9 months, showed some differences in the relative reductions during follow-up. The most evident relative reduction of overall 60% was seen for IgG4, with 65% among patients with clinical improvement, versus 29% among patients with no clinical benefit. IgG4 has special characteristics, being the least abundant subclass, with reduced ability to activate Fc-dependent effector functions such as ADCC and complement-mediated cell killing, with stochastic fragment antigen binding (FAB) arm exchange and often bispecific design, although monovalent in antigen binding. IgG4 usually has blocking and inhibitory effects on the target molecule or the immune response, and autoimmune diseases associated with IgG4 autoantibodies are often more responsive to anti-CD20 B-cell depletion intervention (46). Whether the present IgG4 data has pathomechanistic implications for ME/CFS, remains to be elucidated.
 
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