Daratumumab n= 10 Trial Norway - encouraging preliminary results Oct 2024

[dr. Arf]

Intermediate encouraging results from Daratumumab Pilot study in Norway n= 10

Recently in October, Norwegian researchers presented preliminary results
- The initial response rate is promising and it’s well tolerated.
- A larger RCT trial is going to be planned (in 2025?j

It’s a 15 minute presentation - check between minute 13 and 15 for most essential slides
‘https://youtu.be/nCik6NamXdo’

So Daratumumab = a Mab = monoclonal antibodies
- in my laymen terms: it targets - reduces antibody production / immunoglobins

**
I attached the most interesting slide showing 3 patients : 2 responders + 1 non-responder

2 responders:
- seem to be moderate ME CFS - according to steps (2000/day)
- IgG / immunoglobines go down to 4 g/L (from 8 to 4)
- at the same time daily steps increase from around 2000 to around 10,000 in 1 year
- physical function and fatigue score improve a lot (SPF PF + DSQ score).

1 non-responder:
- IgG went down from 10 to 8 IgG g/L
- 2000 Steps per day and fatigue scores went down 18 weeks after treatment and recovered 30 weeks after treatment
- so patient dipped for 4 months - and recovered to the same baseline (more or less)

*note if I remember correctly, also responders in the cyclophosphamide (CycloME) study lowered their IgG levels (?)

**
Although it’s only 3 patients from a small promising pilot there are still some interesting questions:
1) How come the Daratumumab didn’t really lower IGG much in 1 non-responder patient ?
2) what is the correlation with patients (a) improvements ME CFS, and (b) getting lower initial IGG because of Dara treatment (and cyclophosphamide) ?
-could this indicate there is some auto-immunity ME CFS subgroup?
- or could lowering antibodies / IgGs lead to other mechanisms improving ME CFS and PEM ?

 

[dr. Arf]

More info:

1. Interesting to know is dr. Habets from Germany is currently doing his mini trial n=6

https://x.com/l_habets/status/1862512893238841591?s=61


2. I’m also Including 1 other slide showing the Pilot study design

3. And a slide from a previous presentation Tracking one of the Dara responder patients
- week by week with steps and resting heart rate

 

[Finnishgunner4]

do you think it’s probable daratumumab would work if rituximab helped with your mecfs but eventually you relapsed?

 

[Rufous McKinney]

So Daratumumab = a Mab = monoclonal antibodies

Does this substance have fewer side effects than rituximab?

Checking online, how do these two differ?

"Daratumumab and rituximab are both monoclonal antibodies used to treat certain cancers and autoimmune diseases, but they target different proteins on immune cells. Daratumumab targets CD38, a protein found on the surface of multiple myeloma cells and some other immune cells. Rituximab targets CD20, a protein found on B cells. This difference in targeting leads to different mechanisms of action and therapeutic applications. "



- I have a non-hodgkins lymphoma diagnosis; currently I have no observable symptoms; I test positive for Hep B , which means I think that I would have to take some serious antivirals, to stop a Hep B reactivation which could kill me as I understand it, should I ever try Rituximab.

 

[dr. Arf]

Does this substance have fewer side effects than rituximab?

I don’t know. From what I heard from the trial from the Norwegian n=10 and from the German doctor N=6 My impression is that it’s not as bad As Ritux.

attached image shows the difference.
Apparently, Dara is more effective because it will work more broadly also the bleeding long lived plasma cells.

- I have a non-hodgkins lymphoma diagnosis; currently I have no observable symptoms

ouch, really ?
i m sorry

on a “positive note” - this might give you access to treatments like Ritux, Dara, and cyclophosphamide or even a Stem cell translation.

I have heard quite a few ME-remission stories from Cancer ME-patients specifically cyclophosphamide For lymphoma, leukemia or breast cancer.
- If you want, I can send you list (I have them in an Excel sheet)

 

[dr. Arf]

From the Norwegian ME-presentation from prof Fluge today, these snippets on daratumumab
N=10 pilot.
Secondhand information from a bluesky post - that was again posted on Norwegian Facebook ME-research group.
https://bsky.app/profile/oppklipt.bsky.social/post/3lomv6fzgpc2i

- 6 of 10 could walk 10,000 steps after treatment, the other 4 showed no change
- there is probably a relation with lowering of IgG

discussion on S4ME:
https://www.s4me.info/threads/2022-pilot-study-in-norway-daratumumab-in-me-cfs.28098/page-4

 

[bad1080]

if they now knew what the difference is between the 6 who got better and the 4 who did not, that would be interesting

 

[Rufous McKinney]

ouch, really ?
i m sorry

its a low grade version and Treatment is not advisable at the present time. My doctor told me to get in a hammock and that it would go away. So that is my current view: it went away.

this might give you access to treatments like Ritux

I test positive for Hep B. Rituximab could cause a reactivation and kill me. Maybe there is some antiviral given in order to get through all that. It sounds like a bad plan for me, frankly.

 

[dr. Arf]

if they now knew what the difference is between the 6 who got better and the 4 who did not, that would be interesting

They are hinting that there might be a correlation with:
- the more IgG levels go down - more chance response

 

[ryanc97]

I'll just say this. Look at the scatterplot of NK cells in x10^6/L vs score/treatment effect with a Spearman correlation of 0.77.

Look closely. If your NK cells are above 150, then according to the scatter you will be a responder. It's those with NK cells in the <150 range are non-responders.

It's a strong correlation. So you could go and get an NK cell test, and compare your score to the scatter, and if its high enough, then Daru could work for you in theory - according to this study.

Now the problem is small n and female only.

I don't think the IGG effect scatter is that significant there isn't any trend. But the NK cell count being predictive of response is quite strong. You can almost draw a straight line through it and get not a bad R2.

@dr. Arf what do you think? I heard there's going to be another trial?

 

[cfs since 1998]

I'll just say this. Look at the scatterplot of NK cells in x10^6/L vs score/treatment effect with a Spearman correlation of 0.77.

Look closely. If your NK cells are above 150, then according to the scatter you will be a responder. It's those with NK cells in the <150 range are non-responders.

It's a strong correlation. So you could go and get an NK cell test, and compare your score to the scatter, and if its high enough, then Daru could work for you in theory - according to this study.

Now the problem is small n and female only.

I don't think the IGG effect scatter is that significant there isn't any trend. But the NK cell count being predictive of response is quite strong. You can almost draw a straight line through it and get not a bad R2.

@dr. Arf what do you think? I heard there's going to be another trial?

Yes, they have started a double-blind trial with n=66, and patients will need a minimum number of NK cells to enroll in the trial.

The NK cells are needed for the daratumumab to work. It "marks" the CD38 cells, and causes NK cells to kill them.

"The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer." Wikipedia.