ME and PEM recovery via Cyclophosphamide (personal story)

[siobhanfirestone]

I am thinking if its useful to be able to post things like the actual data, including IgG and other values and timelines and stuff but in a write up, but then again if i do that i feel it needs a researcher to do so and could potentially be published as a case study, not sure how to go bout that as the doctor wont be interested in that.

 

[Hutan]

· For a person who starts off with moderate ME/CFS and has some medical attention, being able to do unlimited moderate exercise or better one year after treatment begins is rare, but it happens for some without any treatment that you’d expect to dramatically affect ME/CFS.

· Improvement from moderate ME/CFS to a much better level of physical functioning by 1 year is not rare at all (see 38% improving by 20 or more points on the SF36PF and 22% improving to SF36PF≥75 above).

Great analysis Karen.

@siobhanfirestone, you are right to point out that the selection criteria for the PACE trial was loose, and that it is likely that some people who didn't have ME/CFS were included, and their recovery odds may be different to a person with ME/CFS (including PEM).

Against that though is the fact that the people Karen analysed were in the group with the biggest nocebo effect. They were basically in a waitlist control, reading the newsletters about how wonderful GET and CBT were. People were incentivised to keep reporting low function in order to offered the treatments they hoped to get when they volunteered for the study. And the outcomes are subjective - if someone felt better, they might still interpret that negatively.

Another point is that it can be hard to know if you actually have ME/CFS. We've seen smart people very familiar with the ME/CFS criteria find out that they have something else that explains their symptoms (although sometimes people wonder if they have both the other conditions and ME/CFS). I know the criteria off by heart, I feel certain I experience PEM, I've shown the 'typical ME/CFS' response to a 2-day CPET. And, even so, it would not surprise me at all to find that I don't have ME/CFS, and instead have something else.

Do I think your experience is a clue for some with an ME/CFS label? Yes, possibly, and it's worth thinking about. Can we be sure that it means that some aspect of what cyclophosphamide does (or even what the combination of drugs that you had does) is curative? No, I don't think so.

I'll give you the example of my family to illustrate why some of us are hesitant. Three of us got ME/CFS in my family following what seemed to be a viral illness, at the same time. One of us essentially recovered after two years. If she had started cyclo at 20 months, when her symptoms were still serious enough to have made some people prepared to do that, the difference between feeling awful on the cyclo and the naturally recovered state after two years would have been substantial. She might have concluded that the cyclo fixed her, while having the (in her case, unnecessary) risk of cancer and infection.

 

[siobhanfirestone]

Great analysis Karen.

@siobhanfirestone, you are right to point out that the selection criteria for the PACE trial was loose, and that it is likely that some people who didn't have ME/CFS were included, and their recovery odds may be different to a person with ME/CFS (including PEM).

Against that though is the fact that the people Karen analysed were in the group with the biggest nocebo effect. They were basically in a waitlist control, reading the newsletters about how wonderful GET and CBT were. People were incentivised to keep reporting low function in order to offered the treatments they hoped to get when they volunteered for the study. And the outcomes are subjective - if someone felt better, they might still interpret that negatively.

Another point is that it can be hard to know if you actually have ME/CFS. We've seen smart people very familiar with the ME/CFS criteria find out that they have something else that explains their symptoms (although sometimes people wonder if they have both the other conditions and ME/CFS). I know the criteria off by heart, I feel certain I experience PEM, I've shown the 'typical ME/CFS' response to a 2-day CPET. And, even so, it would not surprise me at all to find that I don't have ME/CFS, and instead have something else.

Do I think your experience is a clue for some with an ME/CFS label? Yes, possibly, and it's worth thinking about. Can we be sure that it means that some aspect of what cyclophosphamide does (or even what the combination of drugs that you had does) is curative? No, I don't think so.

I'll give you the example of my family to illustrate why some of us are hesitant. Three of us got ME/CFS in my family following what seemed to be a viral illness, at the same time. One of us essentially recovered after two years. If she had started cyclo at 20 months, when her symptoms were still serious enough to have made some people prepared to do that, the difference between feeling awful on the cyclo and the naturally recovered state after two years would have been substantial. She might have concluded that the cyclo fixed her, while having the (in her case, unnecessary) risk of cancer and infection.

Was she getting worse before that though
That’s what people seem to miss here ….

 

[Hutan]

Was she getting worse before that though
That’s what people seem to miss here ….

No, she wasn't getting worse, although there were fluctuations.

If you were getting worse up until the cyclo started working, then that does make your experience more compelling, I agree. But, and sorry to be annoying, but what if it was the various other treatments that you were trying before the cyclo and the cyclo itself, the side effects and the PEM from the exertion, the travel related to those, that made you feel worse?

 

[siobhanfirestone]

No, she wasn't getting worse, although there were fluctuations.

If you were getting worse up until the cyclo started working, then that does make your experience more compelling, I agree. But, and sorry to be annoying, but what if it was the various other treatments that you were trying before the cyclo and the cyclo itself, the side effects and the PEM from the exertion, the travel related to those, that made you feel worse?

the treatments just before cyclo also hypothetically worked by reducing IgG, so if that was the case I believe it’s just more evidence for the theory. All I can say is it took to <4 IgG for me to get that therapeutic effect but after all treatments and before cyclo it was a healthy 8.

I don’t think say paxlovid in early 2023 had any role at all though.

I don’t think case studies can like prove a causal role that’s for more comprehensive studies, but it certainly suggests that there is something to the plasma cell and IgG theory. I see my case as a small contribution to a larger set of data that demonstrates a correlation between the two. It’s not definitive proof nor are we near that, but I’m certainly glad I didn’t dismiss the data found in the IgG focused studies.

I think people need to think of it this way, what is more likely;
1) I magically got better four months into chemo hell from a disease that I was experiencing a reductionin capacity and QoL from, that just so happened to take place at the exact time that my IgG dropped to levels used to treat autoimmune diseases.
2) The correlation between very low IgG and remission, remission = full health not just a bit better, indicated a pathological role in the IgG.

 

[dankeen]

If Siobhan was the only case I would also be skeptical, but her case needs to be viewed within the larger body of evidence. 22/40 trial participants reported some degree of improvement (some temporary) and cyclophosphamide significantly outperformed rituximab and placebo at six years. This is far better than the results for any psychological study.

I am sure there are patients who experienced just as dramatic as fast remissions as Siobhan after the lightning process, but they are probably just outliers of the many thousands of ME patients that have done psychological therapies over the years.

Fluge is quoted in the Norwegian press as saying he has seen 15 cancer patients with ME improve after cyclophosphamide. There have been a few more on twitter who report the same thing. I think we can safely assume the majority of cancer patients were not expecting this.

It is plausible that a subset of ME is immune mediated (even if it is not a conventional autoimmune disease). The evidence for this is
-A lot of patients report disease onset following infection or a vaccine and many report temporary or permanent worsening following subsequent infections
-A higher frequency of autoimmune disease amongst close relatives of ME patients than the general population
-A high rate of allergies and intolerances
-The gender ratio of ME is similar to the gender ratio for some autoimmune diseases

It is therefore plausible that a strong, broad spectrum immunosuppressant could help a subset.

 

[Karen Kirke]

Thanks, @Hutan . You outlined the reasons why I think the data are still relevant really well – you saved me a post!

I think what’s difficult, @siobhanfirestone , is that you’re posting your story – which is fabulous; on a personal level it is so wonderful to hear of someone going from sick to apparently healthy and I and others are delighted for you – on a science forum, so people are responding in sciencey ways. I think all that cautious people are saying on here is that we are not comfortable saying anyone's remission is likely due to cyclo until a randomised, placebo-controlled trial is positive. [Editing to add: or a trial that looks for a dose response, as in @Jonathan Edwards ' post #83 below https://s4me.info/threads/me-and-pe...amide-personal-story.40009/page-5#post-556926]

I think it’s worth looking at the last few publications from Rekeland et al. – i.e. the Norwegian Fluge and Mella group.

In 2020, Rekeland et al. published the results of the cyclophosphamide study. https://pubmed.ncbi.nlm.nih.gov/32411717/ They concluded:

The treatment was associated with long-lasting improvements of ME/CFS symptoms for approximately half of patients. However, due to the lack of a placebo group, response data must be interpreted with great caution. In the further work to find effective treatment, we will consider a new multicenter, randomized, double-blind and placebo-controlled trial with cyclophosphamide [emphasis added].

Another paper by the same group, Rekeland et al. 2022, is also very interesting in this regard. This was not a treatment study. They just followed people with ME/CFS for 6 months using Fitbits and questionnaires. Their data are publicly available. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484698/

Out of 14 patients who were moderate at baseline (SF36PF 30-59 in weeks 1-4):

• 3 reported SF36PF scores that were ≥20 points higher in the final month (weeks 21-24). The biggest jump was 45 points.
• The step count of 4 patients (i.e. 29%) increased by more than 2000 steps in this time period.
• One patient who started at 3900 steps per day finished at 10219 steps per day.
• Another started at 4453 and finished at 8661, all in 6 months of no intervention.

They conclude:

Although we cannot generalize from this small observational study with no intervention, our data underline the difficulties in distinguishing fluctuations in the natural course of the disease from the true effect of an intervention. If similar natural variations in patient-reported and physical activity measures occurred during a clinical trial, they could be wrongfully interpreted as response to an intervention, and could affect conclusions on response and effect sizes.

Then Rekeland et al. 2024 present promising data from a 6 year follow-up, and conclude https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265720/:

After six years, 44.1% of the cyclophosphamide group scored an SF-36 PF of at least 70, and 17.6% of at least 90, suggesting that cyclophosphamide in a subgroup may modulate the disease course in a beneficial way. However, cyclophosphamide carries toxicity concerns and should not be used for ME/CFS patients outside clinical trials. Rather, these data should encourage efforts to better understand the disease mechanisms and to search for targeted and less toxic immune modulatory treatment for this patient group.[emphasis added]

What people are doing on here is just heeding the warnings of these excellent scientists, and learning from long experience of our own remissions and relapses, improvements and deteriorations, treatments tried, and the rituximab rollercoaster.

Edited formatting

 

[dankeen]

In the original study they stated.

“This study shows that cyclophosphamide intervention is feasible for ME/CFS patients. The growing evidence for immune alterations in ME/CFS and the high symptom burden with very low quality of life, we believe can justify use of an immune modulating drug with possible side effects. The treatment period was demanding for most patients, but in total the toxicity was interpreted as acceptable.”

“We nevertheless believe a future randomized trial is warranted.”

They backed down on the idea of widespread use of cyclophosphamide presumably due to backlash from people who don’t understand that this disease causes people to kill themselves and should be treated as seriously as a disease which directly kills people.

One of the Norwegian cancer patients who recovered also endured radiotherapy, surgery and two other chemo drugs all of which left her with new problems. She still said “Thank god I got cancer” because her net quality of life is much better.

 

[Trish]

“This study shows that cyclophosphamide intervention is feasible for ME/CFS patients. The growing evidence for immune alterations in ME/CFS and the high symptom burden with very low quality of life, we believe can justify use of an immune modulating drug with possible side effects. The treatment period was demanding for most patients, but in total the toxicity was interpreted as acceptable.”

“We nevertheless believe a future randomized trial is warranted.”

They backed down on the idea of widespread use of cyclophosphamide presumably due to backlash from people who don’t understand that this disease causes people to kill themselves and should be treated as seriously as a disease which directly kills people.

I don't understand the logic of your comment. Fluge and Mella were very clear that there should not be widespread use of Rituximab after their uncontrolled trial looked promising. They insisted that it was important to do their larger controlled blinded trial first. As it turned out they were right, as is showed no benefit for rituximab compared to controls.

Surely this suggests the same reason applies to Cyclo, that there needs to be a randomised blinded controlled trial before any suggestion of widespread use. Nothing to do with any backlash from anyone.

I can't help wondering why you are so adamant that cyclo should be used more. Do feel free to tell us what your experience with cyclo is if you want to.

 

[Karen Kirke]

In the original study they stated.

“This study shows that cyclophosphamide intervention is feasible for ME/CFS patients. The growing evidence for immune alterations in ME/CFS and the high symptom burden with very low quality of life, we believe can justify use of an immune modulating drug with possible side effects. The treatment period was demanding for most patients, but in total the toxicity was interpreted as acceptable.”

“We nevertheless believe a future randomized trial is warranted.”

They backed down on the idea of widespread use of cyclophosphamide presumably due to backlash from people who don’t understand that this disease causes people to kill themselves and should be treated as seriously as a disease which directly kills people.

Rekeland et al. did not condone widespread use of cyclophosphamide in the 2020 paper. Here's the unedited context of the part you quoted, including the text that preceded and followed it:

The growing evidence for immune disturbances in ME/CFS, experience with cyclophosphamide in other autoimmune diseases, with broad immunosuppressive effects on several lymphocyte subsets including B-cells and T-regs, and the herein reported association between HLA risk alleles and clinical response to cyclophosphamide intervention, support that the observed relief of ME/CFS symptoms could be a drug effect targeting the underlying disease mechanisms. We strongly advise patients and physicians not to use cyclophosphamide for ME/CFS patients outside of clinical trials before a randomized trial has been conducted, to evaluate the possible benefits of the drug. [emphasis added]


Conclusion
This study shows that cyclophosphamide intervention is feasible for ME/CFS patients. The growing evidence for immune alterations in ME/CFS and the high symptom burden with very low quality of life, we believe can justify use of an immune modulating drug with possible side effects. The treatment period was demanding for most patients, but in total the toxicity was interpreted as acceptable. The treatment was associated with long-lasting improvements of ME/CFS symptoms for approximately half of patients. However, due to the lack of a placebo group, response data must be interpreted with great caution. In the further work to find effective treatment, we will consider a new multicenter, randomized, double-blind and placebo-controlled trial with cyclophosphamide. Should this trial prove cyclophosphamide to be beneficial for ME/CFS patients, this could also be important in the search for relevant disease mechanisms. [emphasis added]

[Full paper here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201056/]

 

[dankeen]

Rekeland et al. did not condone widespread use of cyclophosphamide in the 2020 paper. Here's the unedited context of the part you quoted, including the text that preceded and followed it:

I meant widespread use after a randomised trial has been conducted. I thought I made that clear by quoting the part in which they advocate a randomised trial, but maybe I should have quoted the other part.

@Trish I stated my experience with cyclophosphamide earlier in the thread. I am happy to answer any additional questions.

I am adamant it should be used more because I have done a 100+ of hours of research into the risks and I believe that the risk/reward/evidence ratio is strongly favourable. I posted more about the risks and made a case for cyclophosphamide in other threads for anyone who is interested.

 

[Karen Kirke]

I meant widespread use after a randomised trial has been conducted. I thought I made that clear by quoting the part in which they advocate a randomised trial, but maybe I should have quoted the other part.

Thanks for clarifying. In that case, I don't understand why you say

They backed down on the idea of widespread use of cyclophosphamide presumably due to backlash...

How can you back down on something you might have advocated if a trial that has not yet happened were positive? I don't follow.

 

[EndME]

They backed down on the idea of widespread use of cyclophosphamide presumably due to backlash from people who don’t understand that this disease causes people to kill themselves and should be treated as seriously as a disease which directly kills people.

Are we sure about that?

I thought the problem always had to do with the feasibility of a cyclo trial. From what I've understood you cannot meaningfully placebo-control cyclo. So the only answers you'll get will be from some form of randomised controlled trial, with likely insufficient control and possibly relying on somewhat subjective outcome measures, i.e. you'll be dealing with some of the same problems that occured in the PACE trial.

I always thought that if anybody would discover some ME/CFS pathology that could be tracked as part of trials, something like a cyclo trial would become much more feasible even if you cannot placebo control it. That is to say we can't advocate for widespread use without a well conducted phase 2/3 study and one currently cannot meaningfully trial cyclo in a larger trial, i.e. it has nothing to do with not taking ME/CFS seriously.

 

[Karen Kirke]

we can't advocate for widespread use without a well conducted phase 2/3 study and one currently cannot meaningfully trial cyclo in a larger trial

Thanks so much for explaining that, @EndME , and for doing it so clearly. I did not know that, and now I do.

Rekeland et al. give a nice list of possible mechanisms of action for cyclo in ME/CFS in the 2024 paper. Maybe there are less toxic drugs that could test some of them:

inhibition of activated B cells to plasmablasts...The down-regulation of T cells, the impact on several subsets of
lymphocytes and interactions between immune cells, or a reduction in IgG levels -, including putative autoantibodies

 

[EndME]

Thanks so much for explaining that, @EndME , and for doing it so clearly. I did not know that, and now I do.

I'm not sure about any of the things I've said. This was just how I've read the room, which might be very incorrect.

Regarding less toxic drugs to target some of the possible mechanisms above and which is also what the case report here is about:
From what I've vaguely understood Efgartigimod doesn't have too many toxicity concerns and causes an effective reduction in IgG levels. Of course it was trialled in Post-Covid POTS without success, so any trials for ME/CFS seem unlikely (especially because they would be very expensive). I suspect that trial might have included a small handful of ME/CFS patients as well. Maybe someone is interested in retrospective case reports.

Regarding some of the other possible mechanisms (but for drugs that to me appear very toxic): I think one should at some point get case reports of pwME that additionally have developed cancer or an autoimmune disease and are part of a bispecific mAb or CAR-T study. So sort of similar to the original Rituximab case reports or the stories one hears about with cyclo in ME patients with cancer. A problem currently might be they would likely be living in China and I have no idea how recognised or widespread ME/CFS and ME/CFS diagnostic criteria are in China...

Overall I wouldn't be suprised if one can only have really successful trials if one actually has a much better idea about the pathology one is trying to address.

 

[Jonathan Edwards]

If Siobhan was the only case I would also be skeptical, but her case needs to be viewed within the larger body of evidence.

I may have got this wrong but I thought that Siobhan's experience was that improvement came with hypogammaglobulinemia. That is quite plausible. Jo Cambridge and I have spent some time considering the idea that in ME the problem is that IgG is 'generally badly made' in some way rather than auto reactive in a typical sense. I imagine that in the Fluge/Mella trials patients did not become hypogammaglobulinemic, so the data are if anything inconsistent.

22/40 trial participants reported some degree of improvement (some temporary) and cyclophosphamide significantly outperformed rituximab and placebo at six years. This is far better than the results for any psychological study.

But that is all very underwhelming. As Trish says, by six years everyone knew rituximab was a flash in the pan. Cyclo patients would still be hoping. Psychological studies are irrelevant, since we don't think psychology works

I think we can safely assume the majority of cancer patients were not expecting this.

No, but maybe Dr Fluge was. Oystein Fluge is a fantastic scientist and totally honest about what he is doing but he was following a lead.

It is plausible that a subset of ME is immune mediated (even if it is not a conventional autoimmune disease).

Absolutely. That is why Jo Cambridge and I are here and she is looking at antibodies on a broad front. Nobody is denying that. The issue is whether or not a single case of improvement linked to low IgG tells us much. You can't combine it with the other different data on cyclo, apart from anything because that would be post hoc. I think it is of interest. My surprise was your suggestion that it was good evidence of 'response'.

They backed down on the idea of widespread use of cyclophosphamide presumably due to backlash from people who don’t understand that this disease causes people to kill themselves and should be treated as seriously as a disease which directly kills people.

Like who was that? Who is it who didn't understand that people kill themselves? This seems a bit of a stretch.

I am adamant it should be used more because I have a 100+ of hours of research into the risks and I believe that the risk/reward/evidence ratio is strongly favourable.

OK, but I have spent thousands of hours over a period of forty years engaged in the problem of cyclo toxicity, including having to handle my own patients developing and dying of cancers, and designing trials that used cyclo. As far as I can see we have no reliable evidence for cyclo being a good option here and we have the very strongest evidence of serious harm.

The key point for me is that if Siobhan is right that low IgG is what matters cyclo is not an obvious choice. The lowest IgG levels I have seen with anti-B cell agents in trials were with a biologic (either rite or belimumab I think) and mycophenylate.

 

[siobhanfirestone]

Thanks, @Hutan . You outlined the reasons why I think the data are still relevant really well – you saved me a post!

I think what’s difficult, @siobhanfirestone , is that you’re posting your story – which is fabulous; on a personal level it is so wonderful to hear of someone going from sick to apparently healthy and I and others are delighted for you – on a science forum, so people are responding in sciencey ways. I think all that cautious people are saying on here is that we are not comfortable saying anyone's remission is likely due to cyclo until a randomised, placebo-controlled trial is positive.

I think it’s worth looking at the last few publications from Rekeland et al. – i.e. the Norwegian Fluge and Mella group.

In 2020, Rekeland et al. published the results of the cyclophosphamide study. https://pubmed.ncbi.nlm.nih.gov/32411717/ They concluded:


Another paper by the same group, Rekeland et al. 2022, is also very interesting in this regard. This was not a treatment study. They just followed people with ME/CFS for 6 months using Fitbits and questionnaires. Their data are publicly available. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9484698/

Out of 14 patients who were moderate at baseline (SF36PF 30-59 in weeks 1-4):

• 3 reported SF36PF scores that were ≥20 points higher in the final month (weeks 21-24). The biggest jump was 45 points.
• The step count of 4 patients (i.e. 29%) increased by more than 2000 steps in this time period.
• One patient who started at 3900 steps per day finished at 10219 steps per day.
• Another started at 4453 and finished at 8661, all in 6 months of no intervention.

They conclude:


Then Rekeland et al. 2024 present promising data from a 6 year follow-up, and conclude https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265720/:


What people are doing on here is just heeding the warnings of these excellent scientists, and learning from long experience of our own remissions and relapses, improvements and deteriorations, treatments tried, and the rituximab rollercoaster.

Edited formatting

scepticism is fine and expected, but you cant have a randomsied placebo controlled trial with chemo, at all. trust me on this, when you spend days vomiting after. they use the ritux failed data to do the same thing

that 36 questionnarire thing doesnt capture my sickness at all that was 100% PEM and brain fog driven, so in all honetsy im not sure how useful it is, i think they should develop a seperate questionnaire for it tbh

 

[leokitten]

Is there a reasonable less toxic alternative to cyclo with same moa? Could also be a combination of other drugs that effectively do the same thing?

 

[siobhanfirestone]

I may have got this wrong but I thought that Siobhan's experience was that improvement came with hypogammaglobulinemia. That is quite plausible. Jo Cambridge and I have spent some time considering the idea that in ME the problem is that IgG is 'generally badly made' in some way rather than auto reactive in a typical sense. I imagine that in the Fluge/Mella trials patients did not become hypogammaglobulinemic, so the data are if anything inconsistent.



But that is all very underwhelming. As Trish says, by six years everyone knew rituximab was a flash in the pan. Cyclo patients would still be hoping. Psychological studies are irrelevant, since we don't think psychology works



No, but maybe Dr Fluge was. Oystein Fluge is a fantastic scientist and totally honest about what he is doing but he was following a lead.



Absolutely. That is why Jo Cambridge and I are here and she is looking at antibodies on a broad front. Nobody is denying that. The issue is whether or not a single case of improvement linked to low IgG tells us much. You can't combine it with the other different data on cyclo, apart from anything because that would be post hoc. I think it is of interest. My surprise was your suggestion that it was good evidence of 'response'.



Like who was that? Who is it who didn't understand that people kill themselves? This seems a bit of a stretch.



OK, but I have spent thousands of hours over a period of forty years engaged in the problem of cyclo toxicity, including having to handle my own patients developing and dying of cancers, and designing trials that used cyclo. As far as I can see we have no reliable evidence for cyclo being a good option here and we have the very strongest evidence of serious harm.

The key point for me is that if Siobhan is right that low IgG is what matters cyclo is not an obvious choice. The lowest IgG levels I have seen with anti-B cell agents in trials were with a biologic (either rite or belimumab I think) and mycophenylate.

As said before i am invisioning a future where i get this again, so a non-cyclo drug is essential for me in the future. I hope dara passes, but regardless I eill find a way. If patients can get something as safe as dara and it has good efficacy....to have the remission I have now witohut having had to deal with chemo and getting my bladder checked yearly would be great. We will have to wait and see. I just was not going to wait because MAID was the only other option for me to be blunt.

 

[siobhanfirestone]

Is there a reasonable less toxic alternative to cyclo with same moa? Could also be a combination of other drugs that effectively do the same thing?

yes hopefully, there are a bunch of drugs but 1) IgG lowering is hard and dangerous for reasons said in this forum. 2) The norwegians are trialing dara for this very reason 3) There are up coming things like CAR-T that are much better for classic autoimmune conditions but they often focus on b cell depletion not IgG as in other studies, and its very expensive and still isnt 100% success.
I dont know if anyone has any indication when the case studies from dara will be released but we are aware some responded to remission level, or at least 1 from a presentation about a year ago.