Teclistamab for ME/CFS

[ryanc97]

I normally lurk in these threads but made an account to comment here.

I irresponsibly tried teclistamab treatment for my now 9 year long ME/CFS. I'm moderate/severe.

I followed the autoimmune protocol with teclistamab (2 full doses after step up). My IgG went from 10+ to 2. I'm now around 6months after treatment.

The treatment itself was rough and send me into severe for a month due to the side effects and Cytokine Release Syndrome. This was to be expected. Unfortunately my immune system vanished but I experienced ZERO improvements. Not even in POTS related symptoms.

I am feeling worse still than my pre-teclistamab baseline. Probably because I have low immune and survive on IVIG for now. Yes I had positive GCPR antibody titers.

For me, this was not worth the money, energy and time unfortunately and I don't think Dara, Tecli or even CAR-T will be the holy promised land for ME/CFS. Maybe Sjögren type subset could benefit more here.

Conclusion N=1 but it's not "just bad plasma cells or antibodies"

Im my group we have enough evidence Teclistamab doesnt work at all I would say 4 people did full dose Tecli, so if you were one of them that did it, I guess you might be already in our group anyway, then of course thank you for doing it anyway, at least we get to learn from this.

My take is, the bad LLPCs for whatever reason don't have BCMA on them. For whatever reason. Beacuse the P1 results still hold, so Dara does work (but not in everyone) and Tecli does not (everyone who tried it failed).

 

[Rick Sanchez]

This is the Rituximab p1. All the 3 patients ''improve'' at the same time here too. Of course the massive difference is that in Dara for 5 of the patients the ''improvement'' persists.

We know from someone who was in the Dara trial who came forward that genuine improvement happened during the trial. Went from wheelchair to working in healthcare. Now helping to raise money for the study sharing their story publicly.

Maybe it's a combination of FM super placebo and just sheer bad luck.

One interesting thing is we don't even have a SINGLE possible false positive when it comes to Daratumumab and Tecli when it comes to the anecdotes. If we assume 12+ MECFS patients have tried either for long enough at this point (which is a conservative estimate). I would expect at least one placebo improvement if we assume neither works. And yet nothing that compares to the p1 results.

 

[ryanc97]

View attachment 33267

This is the Rituximab p1. All the 3 patients ''improve'' at the same time here too. Of course the massive difference is that in Dara for 5 of the patients the ''improvement'' persists.

We know from someone who was in the Dara trial who came forward that genuine improvement happened during the trial. Went from wheelchair to working in healthcare. Now helping to raise money for the study sharing their story publicly.

Maybe it's a combination of FM super placebo and just sheer bad luck.

One interesting thing is we don't even have a SINGLE possible false positive when it comes to Daratumumab and Tecli when it comes to the anecdotes. If we assume 12+ MECFS patients have tried either for long enough at this point (which is a conservative estimate). I would expect at least one placebo improvement if we assume neither works. And yet nothing that compares to the p1 results.

I think common sense tells you the placebo effect did not happen in P1 at least thats my take.

I think there is some hidden variable predicting response in the Dara study. Is it NK cells and gender? Still possible. But from what ive seen, its probbaly something much deeper.

 

[V.R.T.]

But from what ive seen, its probbaly something much deeper

What do you mean by this?

 

[ryanc97]

What do you mean by this?

I think the Dara signal is real. It’s just we can’t quite figure out why it only worked in those 5.

I thought it was NK cells. Maybe it is, but it’s not that simple anymore bcos we have like 3/4 ppl with good NK that did Dara (all male btw) and nothing.

That’s why I’m hoping Tyler’s study can shed light on it especially when he applies it to p2.

Imo best chance of a biomarker coming from that.

 

[ryanc97]

I normally lurk in these threads but made an account to comment here.

I irresponsibly tried teclistamab treatment for my now 9 year long ME/CFS. I'm moderate/severe.

I followed the autoimmune protocol with teclistamab (2 full doses after step up). My IgG went from 10+ to 2. I'm now around 6months after treatment.

The treatment itself was rough and send me into severe for a month due to the side effects and Cytokine Release Syndrome. This was to be expected. Unfortunately my immune system vanished but I experienced ZERO improvements. Not even in POTS related symptoms.

I am feeling worse still than my pre-teclistamab baseline. Probably because I have low immune and survive on IVIG for now. Yes I had positive GCPR antibody titers.

For me, this was not worth the money, energy and time unfortunately and I don't think Dara, Tecli or even CAR-T will be the holy promised land for ME/CFS. Maybe Sjögren type subset could benefit more here.

Conclusion N=1 but it's not "just bad plasma cells or antibodies"

I don’t think you can say it’s irresponsible. I would say it’s a calculated risk

 

[Rick Sanchez]

I think common sense tells you the placebo effect did not happen in P1 at least thats my take.

I think the Rituximab p1 I have posted is a perfect example of placebo effect taking place given that we know it has as little positive effect as salt water.

From reading history of AIDS but also reading about Cystic Fibrosis I really think that if Daratumumab worked, and worked for just 30 % of patients, we would see positive anecdotes and an absolute frenzy in desperate MECFS and long covid patients trying to get the medicine and we would see countless positive anecdotes on Reddit. Screenshots from positive anecdotes shared from private MECFS Facebook groups.

Instead we've had absolutely nothing. In fact all we really have is patients bravely coming forward and warning others about their negative experiences.

I can only reiterate that anyone even considering these treatments off label should stop right now and just wait. Too dangerous.

 

[V.R.T.]

From reading history of AIDS but also reading about Cystic Fibrosis I really think that if Daratumumab worked, and worked for just 30 % of patients, we would see positive anecdotes and an absolute frenzy in desperate MECFS and long covid patients trying to get the medicine and we would see countless positive anecdotes on Reddit. Screenshots from positive anecdotes shared from private MECFS Facebook groups.

I think you may be thinking far more people have tried it than have actually tried it. It's not easy to get a hold of or administer without supervision

 

[MElonman]

Im my group we have enough evidence Teclistamab doesnt work at all I would say 4 people did full dose Tecli, so if you were one of them that did it, I guess you might be already in our group anyway, then of course thank you for doing it anyway, at least we get to learn from this.

My take is, the bad LLPCs for whatever reason don't have BCMA on them. For whatever reason. Beacuse the P1 results still hold, so Dara does work (but not in everyone) and Tecli does not (everyone who tried it failed).

I'm not part of a group or hospital, but have seen some people on Twitter mention Habets and his low dose regimen. Didn't know others tried full dose. Unfortunate that no one improved.

If CD38 is truly the key it would surprise me cause it overlaps a bit with BCMA cells. You'd expect at least some improvements on Teclistamab then

 

[Jonathan Edwards]

My take is, the bad LLPCs for whatever reason don't have BCMA on them. For whatever reason. Beacuse the P1 results still hold, so Dara does work (but not in everyone) and Tecli does not (everyone who tried it failed).

The numbers are hard to square with that, I think.

LLPC make about 80% of antibody, judging by use of rituximab in various diseases. We have here a report of IgG going from 10 to 2, so that must be hitting most LLPC, otherwise it would be 10 to 8.

 

[ryanc97]

I'm not part of a group or hospital, but have seen some people on Twitter mention Habets and his low dose regimen. Didn't know others tried full dose. Unfortunate that no one improved.

If CD38 is truly the key it would surprise me cause it overlaps a bit with BCMA cells. You'd expect at least some improvements on Teclistamab then

Oh wow, very interesting. So you are doing it alone

My group has like 4 full dose teclistamab, no improves, done start of the year. For Dara, similar but have like 1 or 2 partial responders, with one responder improving a lot in fatigue (can wake up early morning, not tired)

 

[ryanc97]

The numbers are hard to square with that, I think.

LLPC make about 80% of antibody, judging by use of rituximab in various diseases. We have here a report of IgG going from 10 to 2, so that must be hitting most LLPC, otherwise it would be 10 to 8.

well if these malfunctioning LLPC don’t have BCMA, then that model works

 

[ryanc97]

I think you may be thinking far more people have tried it than have actually tried it. It's not easy to get a hold of or administer without supervision

Yes and don’t forget cost. In the US it’s 10k a dose and my Chinese source has it at 1.5k.

Because I live in Asia it makes sense to fly there to get it. But an American or European needs to price in tickets too

 

[Jonathan Edwards]

well if these malfunctioning LLPC don’t have BCMA, then that model works

Why would they be malfunctioning? Autoantibody producing plasma cells are in all other respects entirely normal as far as we know.

 

[ryanc97]

Why would they be malfunctioning? Autoantibody producing plasma cells are in all other respects entirely normal as far as we know.

I don’t know, I’m just working backwards to arrive at a conclusion.

 

[Jonathan Edwards]

I don’t know, I’m just working backwards to arrive at a conclusion.

I can see that but in the process you are introducing a requirement that nobody has ever found any evidence for in analogous situations. It is a bit like saying that, OK, the murderer must have had two left feet.

 

[ryanc97]

I think the Rituximab p1 I have posted is a perfect example of placebo effect taking place given that we know it has as little positive effect as salt water.

From reading history of AIDS but also reading about Cystic Fibrosis I really think that if Daratumumab worked, and worked for just 30 % of patients, we would see positive anecdotes and an absolute frenzy in desperate MECFS and long covid patients trying to get the medicine and we would see countless positive anecdotes on Reddit. Screenshots from positive anecdotes shared from private MECFS Facebook groups.

Instead we've had absolutely nothing. In fact all we really have is patients bravely coming forward and warning others about their negative experiences.

I can only reiterate that anyone even considering these treatments off label should stop right now and just wait. Too dangerous.

I’ve also explained before why there is a funnel that leads to single digit numbers of people trying Dara.