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

So firstly, a disclaimer, I might be in a weird MECFS subgroup. However this is my experience as a mild patient who tried exercising and pushing my body. When my parents hired a very experienced personal trainer to fix my ´´problem``. The program was as follows. Monday, Tuesday, Thursday and Friday.

Neither of us had really heard of MECFS. The exercise chosen was strength training. Squats, deadlifts and all that kinda stuff. One of the quickest things my personal trainer picked up on was that I was simply unable to repeat the workout if I had not gotten any rest. This, according to my personal trainer should never ever happen when you are a newbie young male. You basically make nothing but progress in the beginning. It wasn`t lack of willpower, it was genuinely impossible for me to repeat what I had lifted the day before. Sometimes quite significantly, which is especially problematic when you are bench-pressing. Very quickly the program began allowing for me to rest every single time.

The same massive decline in performance followed whenever my MECFS ´´broke out`` as well. Which followed either random MECFS fluctuations, or after acquiring actual illness which it then took my body weeks to recover from. Mostly I was, and still am unable to tell which of the two is actually occurring. So we ended up doing a lot of yoga instead of exercise when I showed up like this, because my trainer started getting worried about ´´pushing me`` and pushing me was senseless since I could not perform, even if my life depended on it.
 
That's a rather odd statement from a personal trainer about beginners making constant progress, because in reality beginners often struggle with pretty bad DOMS lasting for days when they start, since their muscles are not used to strength training. Training regularly reduces the likelihood of DOMS but it often does not completely go away and even trained people experience it every once in a while.

This is basically the reason why people often have a "leg day" or an "arm day" etc in strength training, so you can work out every day without working on the same muscle group two days in a row. It is common to give those muscles such a rest for a day even without DOMS but such a break is especially useful when someone is likely to get DOMS.

DOMS is not the same as ME/CFS though, I just find it weird that the personal trainer said such things. I mean this is something that can very much happen to healthy beginners too that they do a strength training session and then they really struggle the next day due to the muscle pain that comes with DOMS.
 
I’ve had more trouble moving my limbs when in a crash than what I ever experiences at ~6000 meters altitude or after a week long skiing trip. But it feels different - it’s not just even more of the exertion-fatigue from when I was healthy.
 
I’ve also had the same experience with exercise when I was moderate. The patterns of symptoms and my ability to perform simply didn’t match anything they’d seen before. They were usually quite shocked when I told them how the exercise affected me. But they didn’t make any adjustments..
 
Remembering back to when I was first unwell, the fatigue felt to me like the type of fatigue you get with flu or intoxication. It is/was different in that it feels much more unpleasant but it is/was similar in that I can always push through, particularly with adrenaline.

For me, pushing through can feel similar to a sprint finish when I used to do middle distance athletics and cross-country. The switch in my brain to push through is similar to the switch I used to turn on to sprint finish.

(I’ve never thought about it before but it occurs to me that not everbody has the ability to sprint finish. I wonder if there may be a similarly between this and how people describe and experience their fatigue/PEM.)

When I was bed-bound for 7 years (following repeated attempts to push through) the intensity of the fatigue felt very like how I hear people describing hitting the wall when running a marathon – the point at which you run out of glycogen. It isn’t a lethargic fatigue, it’s an intense fatigue, as though I am running through the wall in a marathon, not the relief-type fatigue that you get after you have crossed the line.

I don’t know if these two types of fatigue I experience * – the intoxication-type and the wall-type – may be physiologically different. But the similarity is that I can always push through if needed, and the effect of pushing through always makes me worse (even when I kid myself that it might be different this time, as I still do after 33 years, particularly when my adrenaline is flowing.)

There is one more sensation I get which I hope may be useful to describe. When I was still walking a bit, I could feel a change in my muscles when I knew I was going past the point that would induce PEM (although I hadn’t heard of PEM at that time). It’s very hard to describe – not like anything I experienced as a healthy person – but it was like some type of acid that I could feel building building up in my muscles, although not the same as the feeling of lactic acid build-up that I knew well from athletics. I would not get breathless, but from that point onwards every step would increase symptoms (which felt like some type of hypoxia) and I would know that I was going beyond my envelope.

I think the lack of breathlessness is relevant. It often feels like I might feel better is I was breathless – as though my body is screaming for more oxygen but somehow the signal to effect that is being blocked.

Although I hardly walk now, I get a similar feeling when I’m doing other activities, which signal to me that I am pushing my envelope and ought to stop. The big frustration, and what makes it so hard, is that stopping doesn’t make me feel better, it just prevents me from feeling worse later.

I should also add that I am in the group of people who never feel as though I recover. My core symptoms are always present and I always feel unwell to a greater or lesser extent. Avoiding PEM for me is about maximising how much I can do, and minimising how awful I feel, within a state of always feeling unwell.

* There is also possibly a third type of fatigue that i experience – one that feels more like an immune/allergy response. This can be triggered by perfume, cleaning polish, pollen, certain foods etc. If something triggers a reaction the “fatigue” for want of a better words becomes instantly worse. This may be an exacerbation of the intoxication-type fatigue. And it also seems that it can be induced by aerobic activity beyond a certain point.
 
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My muscle fatiguability and pem go hand in hand and can fluctuate hour to hour it’s quite remarkable. To me it definitely feels like my nerves are sensitised all the time but even more so in pem. It can be quite a quick signal to occur. Immediate during/soon after the activity, fluctuation hour to hour within the day and then a delayed version for me often 24-48 hours later.

At my worst my legs were so rapidly fatiguable any movement e.g bending to sit down would make my legs shake. Even now if I try and do one leg raise I might be able to do one but if asked to repeat it it would become progressively harder, the intensity of my nerve pain/lactic acid type feeling increases and the muscles will shake. These symptoms intensify during pem even lifting a finger or rolling over in bed.

When my muscles are shut down so to speak I find it hard to coordinate them as well and lose balance. Like my head isn’t connected to my body and controlling the muscles adequately. Adrenaline and often eating can temporarily over-ride this problem/signal and I may get a second wind yet to flare and be forced to stop when pem fully hits. I’m not sure if what I describe is similar to others experience. I do have small fibre neuropathy and pots.

However I have experienced these same set of symptoms just at different levels of severity - mild, to moderate then severe then back to moderate-severe. I’m in this state constantly so for me pem isn’t a defined state it’s just a worsening of my baseline symptoms and then maybe a few more added in for good measure.
 
Jaybee00 said:
“Protocol ver. 1.6: Amended treatment protocol; this will apply to four additional patients included in Q1 2025, as well as retreatment of one previously included patient with partial relapse. Patients will receive the first daratumumab subcutaneous injection at week 0. For patients with signs of clinical response after the first injection, a second injection will be given at 24 weeks, and a third injection at 48 weeks.

At week 10, if there are no signs of a clinical response, a second daratumumab injection will be given, and, subject to a clinical response, the third and fourth injection will be given at week 24 and 48. If patient experiences no response after the second injection, no further daratumumab will be given.”

Can be found here.

Search for clinical trials - EMA
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@Jonathan Edwards does this amended protocol seem sensible to you?

If I recall correctly, you stated earlier (somewhere) that one initial dose of Daratumumab would be sufficient to deplete LLPCs. This protocol will only be given to several patients in the extended pilot project and it consists of only 3 injections at weeks 0, 24 and 48. For patients who don’t respond by week 10 an additional injection will be given then.
 
Robert 1973 said:
I think the lack of breathlessness is relevant. It often feels like I might feel better is I was breathless – as though my body is screaming for more oxygen but somehow the signal to effect that is being blocked.

Although I hardly walk now, I get a similar feeling when I’m doing other activities, which signal to me that I am pushing my envelope and ought to stop. The big frustration, and what makes it so hard, is that stopping doesn’t make me feel better, it just prevents me from feeling worse later.

I should also add that I am in the group of people who never feel as though I recover. My core symptoms are always present and I always feel unwell to a greater or lesser extent. Avoiding PEM for me is about maximising how much I can do, and minimising how awful I feel, within a state of always feeling unwell.
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This sounds very familiar to me - both the desperate need for oxygen without breathlessness and the unrested, shifting shades of feeling unwell rather then discrete PEM / non-PEM or symptomatic / non-symptomatic states.

With regard to the former, I have always assumed that this is what pwME are referring to when they talked about experiencing "air hunger", though perhaps that is actually a different symptom (at least for some)?

With regard to fatiguability, my own experiences also gel with those described by most here: there is a sort of profound, heavy weakness and lack of function that settles in (sometimes gradually, sometimes quite swiftly) and which does not seem quite the same as any fatigue I can recall experiencing during my healthier days, no matter how great or prolonged the exhaustion. As Jaded notes, this can fluctuate over quite short periods of time and, much like hotblack referenced above, a repeated hand grip test appeared to suggest that this is something quantifiable and which could be replicated/induced quite simply.
 
Wyva said:
That's a rather odd statement from a personal trainer about beginners making constant progress, because in reality beginners often struggle with pretty bad DOMS lasting for days when they start, since their muscles are not used to strength training. Training regularly reduces the likelihood of DOMS but it often does not completely go away and even trained people experience it every once in a while.

This is basically the reason why people often have a "leg day" or an "arm day" etc in strength training, so you can work out every day without working on the same muscle group two days in a row. It is common to give those muscles such a rest for a day even without DOMS but such a break is especially useful when someone is likely to get DOMS.

DOMS is not the same as ME/CFS though, I just find it weird that the personal trainer said such things. I mean this is something that can very much happen to healthy beginners too that they do a strength training session and then they really struggle the next day due to the muscle pain that comes with DOMS.
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My understanding from being surrounded by gym rats and personal trainers. Is that if you are a twenty year old male who eats right, takes the right supplements, rests properly and works out correctly. It pretty much is just non-stop improvement in the first months. It`s why steroids are so alluring. People want the extremely fast progress they made in the beginning, and get frustrated when it slows down significantly.
 
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Yes, you can improve well if you regularly work out. I was commenting on what the personal trainer said that he was surprised that you needed rest and couldn't repeat the workout without rest as a beginner and that you couldn't lift the same weight the next day. He may not be familiar with ME/CFS and PEM but DOMS is a very real phenomenon that usually affects beginners, and so is overtraining syndrome. It is perfectly possible that there are people who are never affected by any of these but a personal trainer should know that these exist and rest is sometimes necessary because of these.

These can affect young men too, they are not immune. They happen because of the difficulty or the intensity of the exercise was more than what the person was used to or because they didn't let their muscles recover. Both DOMS and overtraining syndrome can very much hinder progress if they are bad enough. DOMS can be pretty discouraging for a beginner as they may feel they need to skip 2-4 days for the pain to go away and if DOMS is bad enough it can affect someone's ability to lift the same weight the next day (let alone more) simply because it hurts. I'm not talking about hindrance in long-term progress over months but short-term progress, working out on the next few days. The muscles themselves will of course get stronger in the long term.

Of course these are not comparable to ME/CFS and this is not a comparison I'm trying to make. I'm just saying that a personal trainer should be familiar with these at least as they are very real phenomena. Strength training every day while doing the same workout on consecutive days and lifting heavier and heavier every single time as a beginner is not really realistic and can be pretty bad advice actually. Those muscles in such heavy use need some rest sometimes. (I used to be what you would call a "gym rat" myself before developing ME/CFS. I did insane workouts, thus have some experience myself.)
 
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