Daratumumab, isatuximab (CD38 drugs)

[SNT Gatchaman]

Polyclonal IgG levels remained unchanged, which may be explained by a subset of normal PC with reduced CD38 expression that survived during daratumumab therapy.

That is a pretty striking finding. It seems to suggest that if daratumumab has any efficacy in ME/CFS it is not due to killing plasma cells!

But IGG did go down in Fluge et al.

I wondered that. So things do not necessarily go as pear-shaped as it seemed.

That paper's cohort are patients with myeloma, and they are characterised as extensively pre-treated. Could a reduced CD38 expression on plasma cells more generally be an environmental effect (eg a precursor requirement) before you can even get to the clonal expansion seen in myeloma?

Ie is it possible this observation is not relevant to the ME/CFS context, whose plasma cells are presumptively normal, but just happen to be producing pathological immunoglobulins that we'd like to get rid of?

 

[Rick Sanchez]

From Leo Habets. Translated from German.

Attempted to treat twelve patients already. Patients are so desperate so not going to pretend like this was not somewhat expected, but incredibly worrying.

 

[V.R.T.]

View attachment 29113

From Leo Habets. Translated from German.

Attempted to treat twelve patients already. Patients are so desperate so not going to pretend like this was not somewhat expected, but incredibly worrying.

Is he using the same dosing schedule as the trials? Has he at least checked NK numbers before dosing patients?

I don't approve of his methods but if what he's saying is true that is a bit worrying.

Isn't he using sub clinical doses of teclistamab when he prescribes that anyway?

 

[OrganicChilli]

Is he using the same dosing schedule as the trials? Has he at least checked NK numbers before dosing patients?

No and no. Habets is all over the place and I wouldn't trust anything he says.

 

[EndME]

I don't approve of his methods but if what he's saying is true that is a bit worrying.

I don't think so. There's a strong indication that he has no idea what he's doing or saying so I wouldn't put much value into his observations whether they are negative or positive.

Besides that we have no idea what condition the patients he treats have, maybe they have the spike protein disease he claims he's showed in his patients or the GPCR-aab disease he's claimed to shown to exist or is it the disease he's already cured so many times with Ronapreve? If he can't interpret tests but sees these tests as crucial part of diagnosis what do you end up with?

 

[neophyte32]

Ooohh such a disappointment. This is the only treatment that a significant number of patients are hoping for. If Daratumumab is not effective, what treatment will be?

 

[Jaybee00]

Agree with above….he hasn’t measured NK cells prior to treatment.

 

[Braganca]

Habets starts off w a lower dose too — which he says is for safety — but JE mentioned that it can cause anti drug antibodies (or something) which can then cause the drug to not work.

 

[Rick Sanchez]

I don't think so. There's a strong indication that he has no idea what he's doing or saying so I wouldn't put much value into his observations whether they are negative or positive.

Besides that we have no idea what condition the patients he treats have, maybe they have the spike protein disease he claims he's showed in his patients or the GPCR-aab disease he's claimed to shown to exist or is it the disease he's already cured so many times with Ronapreve? If he can't interpret tests but sees these tests as crucial part of diagnosis what do you end up with?

Just nonsense from him. Sadly he makes these bizarre and seemingly random statements with such assuredness that he is able to convince desperate patients to roll the dice.

I also know that we shouldn`t conclude anything from the P1 study. But it was the ´´healthier`` patients who increased their self-reported scores and steps, and if I had to venture a guess as to what kind of patient would be desperate enough to contact Hebets for an extremely expensive and unproven treatment...

 

[neophyte32]

Just nonsense from him. Sadly he makes these bizarre and seemingly random statements with such assuredness that he is able to convince desperate patients to roll the dice.

I also know that we shouldn`t conclude anything from the P1 study. But it was the ´´healthier`` patients who increased their self-reported scores and steps, and if I had to venture a guess as to what kind of patient would be desperate enough to contact Hebets for an extremely expensive and unproven treatment...

So there is no solution for the most severe cases... even the small hope offered by anti-CD38 therapy is closed to bedridden patients. Yet, among the six people helped by Daratumumab, one patient had been suffering for 35 years.

 

[Utsikt]

So there is no solution for the most severe cases... even the small hope offered by anti-CD38 therapy is closed to bedridden patients. Yet, among the six people helped by Daratumumab, one patient had been suffering for 35 years.

We have no idea yet about how severity might affect any response to Dara (if it actually works). And it wasn’t even tested on the very severe.

 

[Yann04]

So there is no solution for the most severe cases... even the small hope offered by anti-CD38 therapy is closed to bedridden patients. Yet, among the six people helped by Daratumumab, one patient had been suffering for 35 years.

I don’t think it will be if the drug is found to work? We just aren’t at that stage yet.

 

[V.R.T.]

Habets starts off w a lower dose too — which he says is for safety — but JE mentioned that it can cause anti drug antibodies (or something) which can then cause the drug to not work.

Sounds like Habets' anecdata is worth less than nothing in that case.

Can anyone link me to JE's comment about this?

it was the ´´healthier`` patients who increased their self-reported scores and steps

All patients were at least moderate though. The two (i think) severe patients didnt respond but nor did 3 moderate, and what they had in common was low NK cells. I don't think we can draw any conclusions from that about whether it works for severe patients.

If Habets is using the drug in a way that makes it likely not to be effective his anecdotes should just be ignored.

 

[ryanc97]

Is he using the same dosing schedule as the trials? Has he at least checked NK numbers before dosing patients?

I don't approve of his methods but if what he's saying is true that is a bit worrying.

Isn't he using sub clinical doses of teclistamab when he prescribes that anyway?

I have asked Habets in every single tweet he made, I reply him to ask why didn’t he test NK cells and he NEVER responds.

It’s possible the 9/12 had low NK cells. Like <100.

I don’t know why he pushes teclistamab so hard. Maybe he wants to be the guy that pioneered Tecli just like FM pioneered Dara.

What’s worse is he just ignores alll the questions on NK cells.

 

[BrokenBeaktheBrave]

and if I had to venture a guess as to what kind of patient would be desperate enough to contact Hebets for an extremely expensive and unproven treatment...

What does that mean?

 

[Braganca]

Sounds like Habets' anecdata is worth less than nothing in that case.

Can anyone link me to JE's comment about this?

Moreover, serious adverse reactions (including fatal ones) can occur with monoclonals even with small doses. they tend not to be dose dependent. And small doses may produce an anti-drug response that makes further use ineffective.

 

[ryanc97]

Ok, so some research, it seems Iberdomide is the top of my list for NK cell enhancing drugs.

Iberdomide increases innate and adaptive immune cell subsets in the bone marrow of patients with relapsed/refractory multiple myeloma - PMC

Iberdomide is a potent cereblon E3 ligase modulator (CELMoD agent) with promising efficacy and safety as a monotherapy or in combination with other therapies in patients with relapsed/refractory multiple myeloma (RRMM). Using a custom mass cytometry ...

pmc.ncbi.nlm.nih.gov

 

[DHagen]

Jonathan Edwards said:
Moreover, serious adverse reactions (including fatal ones) can occur with monoclonals even with small doses. they tend not to be dose dependent. And small doses may produce an anti-drug response that makes further use ineffective.

Awful to think of the possibility that, in the unlikely event Dara is the "big one," if a clinician should give a pwME an inadequate dose, that person would not only be at risk of dying from it, but could have any hope of recovery destroyed even as pwME all around them recover fully. Truly nightmare fuel, even over and above the horror we all deal with already.