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

[Jaybee00]

Apart from the official phase 2 trial, they are testing dara on additional patients. This is from an updated protocol where everything is unblinded.

Thanks for posting this. It would be nice to know if any of these patients were not female (i.e. males!).

The response by week 2 doesn’t jibe with the response timeline of the initial 6 patients.

 

[Jaybee00]

Link

 

[neophyte32]

Sorry, im severely ill for weeks, bedridden and sensitive, to screen. What the updates mean exactly ? Daratumumab doesn t work so well ?

 

[OrganicChilli]

Sorry, im severely ill for weeks, bedridden and sensitive, to screen. What the updates mean exactly ? Daratumumab doesn t work so well ?

It only works when you use a lot and it's likely that people will have to be retreated after some time.

 

[neophyte32]

It only works when you use a lot and it's likely that people will have to be retreated after some time.

Oohhh damned.

 

[Utsikt]

@Jonathan Edwards is there reason to believe that there’s a chance that not giving enough doses the first time around can reduce the chance of experiencing meaningful benefits from dara on the second try?

 

[Jaybee00]

s there reason to believe that there’s a chance that not giving enough doses the first time around can reduce the chance of experiencing meaningful benefits from dara on the second try?

Well we know that the NK cells are depleted quickly with the first dose. So I’m not sure what doing a couple of injections in a row does. If you space them over a longer period like every 2 months it might make sense because things start to come back.

If you do a couple of shots in a row over a short period you will reach a high concentration in your body because of the long half life of dara, etc. so the high concentration might help with killing stuff.

 

[ChronicallyOverIt]

What’s the timeline on the F&M Dara trial, it already started? Anywhere they post updates, not results, just how far along they are with dosing/how many ppl processed?

 

[Utsikt]

What’s the timeline on the F&M Dara trial, it already started? Anywhere they post updates, not results, just how far along they are with dosing/how many ppl processed?

They’ve started recruitment, and have gotten far more applications than they can accept so hopefully they’ll get enough eligible participants.

The first participants have already received their first doses.

Funding is not completely done yet, expect an update around the end of the year.

I don’t know where updates on the trial will be shared or when, but I’m sure you’ll hear about it here in no time when there is something to know.

Blinding probably means that they won’t know the results until everyone are done.

 

[V.R.T.]

Apart from the official phase 2 trial, they are testing dara on additional patients. This is from an updated protocol where everything is unblinded.

TLDR: 4 LC ME/CFS patients and 1 relapsed patient from the pilot study received a single dose of dara. Their symptoms improved for 1-4 months and F/M concluded that more doses are needed. They expect patients from the pilot trial to relapse who will then be retreated.

It would have been nice if one injection was enough to induce significant improvement/remission. So in that sense we could see this as a bit of a shame. But beyond that it seems to my laymans eye like about what you'd expect if you gave a lower dose than necessary of something that did work.

So if these results were not a placebo effect, what would it tell us about the mechnism of daratumumabs effect in ME/CFS? Does it have any implications for the LLPC vs CD38 doing something else argument?

It is interesting that everyone in the selected group defined by NK cells had some improvement on one dose. Could this be viewed almost like dose response type data? For people with NK cells, one injection gives temporary improvement whereas the full dose from the pilot gives a long lasting remission level improvement?

Im also interested in these patients with severe illness (group four). Is this another planned mini pilot study? Does anyone have info?

I am so impatient for the phase 2 results! I wish we didnt have to wait so damn long!

 

[OrganicChilli]

Im also interested in these patients with severe illness (group four). Is this another planned mini pilot study? Does anyone have info?

Yes, this is like the LC group. They will get injections in Q1/Q2 2026. Three initial injections followed by two more injections half a year later.

So if these results were not a placebo effect, what would it tell us about the mechnism of daratumumabs effect in ME/CFS? Does it have any implications for the LLPC vs CD38 doing something else argument?

I want to know this, too!

 

[V.R.T.]

Yes, this is like the LC group. They will get injections in Q1/Q2 2026. Three initial injections followed by two more injections half a year later.

Thanks! Nervous to hear how that goes as a severe person. Will they all have NK cells above the threshold from the pilot?

 

[OrganicChilli]

Thanks! Nervous to hear how that goes as a severe person. Will they all have NK cells above the threshold from the pilot?

Yes, everyone from group 3 (LC) onwards needs to meet NK cell requirements.

 

[Yann04]

I wonder whether or not it is wise to ask for an NK cell count next time i do bloodwork.

Probably not. I think the stress of having low levels and wondering if I would miss out on dara would be higher than any potential benefit of knowing since its a long time until pilot results anyways.

 

[Utsikt]

I wonder whether or not it is wise to ask for an NK cell count next time i do bloodwork.

Probably not. I think the stress of having low levels and wondering if I would miss out on dara would be higher than any potential benefit of knowing since its a long time until pilot results anyways.

Assuming NK cells are relevant: We don’t even know if the levels are stable over time (if they fluctuate you could time the treatment for when they are high), or if you can boost them artificially and get the same effect as having naturally higher levels.

 

[V.R.T.]

I wonder whether or not it is wise to ask for an NK cell count next time i do bloodwork.

Probably not. I think the stress of having low levels and wondering if I would miss out on dara would be higher than any potential benefit of knowing since its a long time until pilot results anyways.

I've decided not to do it until phase 2 is out or shortly before, for the sake of my sanity. As Utsikt says, we dont know if they are relevant or why yet either.

And if F&M don't test anymore low NK people in a case study before phase 2, we might not know for a while.