Yesterday an investigator contacted me. He has proposed an extensive study to know how RT behaves once Ibrutinib is withdrawn. Patients with RT are coming out and after being given Ibrutinib again they have been biopsied and there is no trace of RT in their nodes.
I told the investigator that there were more patients with the same diagnosis and he is interested in knowing their cases. If anyone wants to participate please contact me. The future of RT depends on us. Knowing how a RT disappears after taking Ibrutinib again, they can study the cure for this terrible diagnosis.
The investigators hardly have cases, so our collaboration for the investigation is necessary.
Friends, something positive we are going to get out of all this.
Priss
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Hi Priss this doesn’t apply to me at the moment anyway. I am 2.5years into ibrutinib but it is great to think someone is wanting to investigate this phenomenon.
They are going to do it because by statistics more cases are going to come out and in this way avoid chemotherapies unnecessarily. That is why it is very important to know what is happening. This researcher told me that he himself saw my lymphoma, I sent him the biopsies. That is why it is not explained why my RT did not act in the two months that it took to treat me. It has no explanation
That is great news that this investigation is happening, Priss! Good for you for bringing people together in this. This phenomenon of fake RT when ibrutinib is withdrawn really does need to be more widely known and understood by all doctors treating CLL patients.
It’s really fascinating. You should ask the investigator to let you get involved in writing this up and give you credit for it as a co author! I have often said we should use this group for reasearch more. I know many worry about sharing their data but case serries are usually well anonymised.
I continue with the proposal to speak with you. The next week I meet with the researcher to do exams and I will inform you and we will look at the way of speaking.
Where is the researcher and what countries will be included in the study? Does he have a written proposal with study information and his contact information which could be shared in other groups or doctors? Good that someone is going to look at this seriously.
Yes, I have a contract for what they are going to do with my blood. They will only use my blood, nothing else. Her studies will be published to the scientific community and my blood will be conserved for those who want to investigate it in order to request it. My anger at the blood bank for further studies.
They want to study because it changes from small lymphocyte to large lymphocyte once Ibrutinib is left for a few days and then restart it.
Sorry I’m not sure I really understand what fake Richter’s is.
So you get RT with biopsy diagnosis after being on Ibrutinib for CLL, then you stop Ibrutinib and restart it? And that clears the large cells from lymph nodes?
I had been on ibrutinib for 3 months ( approx) I had to stop using ibrutinib - 11 days later, I had 3 biopsies taken from one swollen soft lymph gland in my armpit - all of my lymph’s around body were really swollen. I had saturating night sweats for about a week, something I hadn’t had for 8 months, I was fatigued and breathless. All of these symptoms disappeared within the week of their own accord. Biopsies confirmed Richters Transformation. I restarted ibrutinib approx 10 days later, a day after PET scan which showed an absence of any such transformation. I believe I have experienced pseudo- RT. If @Priss69 is correct in her assumption - we make up a very select subset - possibly only 2 in Europe(?)
In Europe that is known there is me and another boy who is going to undergo the study. Where do you dress There are very few cases in the world, I think so far there are only five cases in the United States and in Europe there is me and Miles who lives in England.
Thanks for your explanation! So none of the nodes where showing high activity on PET? And the biopsy from one node shows RT? But then the symptoms cleared by themselves, before you restarted medication? And they continued on Ibrutinib because the PET scan did not show the heightened activity that would follow a transformation to Richter’s?
That is what happened in my case. I am so grateful that Adrian Bloor and his team recognised that I didn’t present as someone with RT - although the biopsies confirmed otherwise - and chose to carry on regular treatment. He surmised that if it were ‘really’ RT, we would know within a month.
The diagnosis of RT post Ibrutinib is complicated by the Ibrutinib withdrawal syndrome which can be very aggressive as explained at iwCLL 2019 ( cllsociety.org/2020/02/iwcl... ) and by the unreliability of PET scans for diagnosis from ASH 2017 ( cllsociety.org/2018/03/ash-... ). The need for biopsy to cinch the diagnosis of RT seemed critical, but the study your referenced seems to even throw that gold standard out the window. This is a critical and obviously poorly understood topic that needs more research. Thanks for highlighting it. I plan to reach out to some researcher that I know and see what they might add.
You have money to finance the study. He told me that he wants to avoid that people who have been falsely diagnosed with RT are not treated with chemotherapy as happened to me.
They also want to see if mine was a safe RT or wrong diagnosis. He himself saw my biopsies because I sent them to him and he saw my lymphoma. What I have never seen is a case of RT that in two months from when RT is diagnosed does not appear. He thought I was a case of RT when I didn't really have RT.
My study will serve to help others. Always help science. If I die, this investigation has been worth it.
Tell him you're on my side, he knows I participate in different sites to try to locate all possible RTs. Little is known about RT and what little you know is the horrible forecast. Now they have come across the false RTs and had no patients to investigate them. That is why I am trying to find all possible patients, as it will be an unprecedented investigation. Elias Campo is known in the United States. He works for the United States.
If you write, tell him that you are on behalf of Toñi (full name deleted, but available via Private Messaging - Admin). It is my real name. He knows that I participate and share my experience here with you.
Toñi, I've deleted your full name now that Dr Koffman has read your reply. While it is appropriate to post this important post of yours unlocked to ensure very frightened people who think they may have RT can find it, I presume you would like to maintain your privacy. Use this site's Private Message/Chat facility to exchange personal contact information.
I put the full name of a patient? I think that my message was not well explained. Of this group I only know one person with RT. I just put the email address of Dr Elias Campo who is the one who is going to do the research.
By the way this is crucial and I would try make sure that every case is also reported to the pharma company. In some Duristrictions the company can take advers event reports direct from patients. But it’s often better for the focotr to do it but they may need promoting. By the company hearing the regulator also heArs and there has to be an assessment. And in these instances a pattern is Emergig That May find its way into the patient and doctor information which is crucial.
My wife with CLL since 2011 had a RT scare in 2013 before treatment with Ibrutinib in 2014.
It all started with very large nodes in her neck that continued to grow over a 7week period.
One of them was removed and the results said RT and that she would need a transplant.
There's much to the story but to make it short after 6 weeks the node was sent to Leeds and the good news it was a virus that made the small B cells look large and mimic a RT.
Thankfully she avoided the chemo and went on a trial with Ibrutinib.
Each time she stops Ibrutinib the nodes come up very quickly and she feels sick.
I don't want any single person to pass because I pass. I don't want anyone to go through aggressive chemotherapy just because of a misdiagnosis. I will do everything possible so that this never happens.
Thank you for this post Priss is this happening only with ibrutinib or other meds also? Thank you for putting this out and for doing something about it.
It seems like it’s an ibrutinib thing. Basically we know ibrutnib works by stopping the cells from multiplying. Think of it like a break applied. But the cells really WANT to multiply. So imagine a car with a very strong handbreak on but the engine at fulll revs. It doesn’t go anywhere so all is good. But if someone takes the handbrake off (stops the ibrutinib) then the car lurches forward really rapidly. Interestingly when lymphocytes multiply rapidly they get large and they look under a microscope very much like the cells of DLBL which is a “diffuse large B cell lymphoma”. Normally when you have cells like that you’d made the diagnosis of Richters transformation (it’s normally DLBL it transforms into) and treat very aggressively typically with Chemo plus venetcolax these days. And it’s a huge worry. BUT there are two clues that it’s not really DLBL in most of these new cases that have been identified. 1. The cells are not really as active as all that and don’t light up on PET scans and 2. There are no symptoms suggesting a rapidly growing blood cancer (the so called B symptoms).
If you imagine our car lurching forward then stalling that’s also what’s been happening in some of these cases and a re biopsy even without any treatment has at time’s showed the cells reverting to a more normal look.
But this is a rare effect and not one that everyone needs to worry about. And for once it’s actually good news since it turns out for several people they didn’t actually have DLBL at all.
There are so many weird things that can happen that we should try not to be alarmed about all of them. But it’s certainly something it’s nice we know about here and chances are there will be some CLL experts even who’ve not heard about this yet (hence the plan to write these handful of cases up).
There are thousands of people on ibrutinib. This has only happened to a small number of those who have had to stop it suddenly. So it’s as I say definitely not a reason to worry about taking ibrutinib. And of course it also doesn’t mean that it’s impossible to actually get a real richters whilst on or off treatment. Again fortunately most of us won’t ever have it though.
Given the much smaller usage of other BTK inhibitors compared to Ibrutinib, it would be wise to consider that pseudo RT may occur following withdrawal from any BTK inhibitor. We may not be aware of this happening yet, due to far fewer patients on other BTK inhibitors.
It only happens with Ibrutinib. I have spent a year trying to find out and find funding for the research. I want people to be treated with chemotherapy and worst of all, the terror of this terrible diagnosis. Doctors say RT equals death. People die and there are very few survivors. The damage caused by both chemotherapy and psychological treatment is terrible. I was destroyed. I came to prepare my own funeral.
We have only seen cases with Ibrutinib so far. I would be interested in plausible mechanisms for why this could only happen with Ibrutinib and not other BTK inhibitors. It might even happen with PI3K inhibitors, because they also block the B Cell Receptor pathway. Keep in mind that the FDA approval of Acalabrutinib for CLL treatment was only 9 months ago. The FDA approval of Ibrutinib was nearly 4.5 years ago and I expect it is still more prescribed than Acalabrutinib. Idelalisib is not much used and not generally used for first line treatment.
We are making progress with RT treatments. It's too slow, but RT is survivable.
Tomorrow I go to Barcelona and on Wednesday I have a consultation with the doctor and exams. I'm going to tell you what they explain to me. All of this gets interesting.
Thank you for all you are doing. Such a vital matter that could affect many of us…
The problems with stopping Ibrutinib suddenly may be wider than the fake RT symptoms. Someone mentioned how when they stopped Ibrutinib, their spleen (which had been shrinking nicely while on Ibrutinib), rapidly expanded and caused a lot of problems. (I think they said it ruptured but I can’t fully remember the case now).
A similar thing happened to me, though I was on Idelalisib at the time, not Ibrutinib. I was told to stop the Idelalisib for a while because I was getting a nasty rash. Within a few days my spleen expanded so rapidly that it ruptured. I needed emergency surgery to save my life.
I had only been on the Idelalisib for two months and it had shrank my spleen and nodes but lymphocytes had gone into the blood and not yet been dispersed. So, there were a LOT of lymphocytes floating around that could flood back into the spleen.
I realise this was a different problem to yours, as I was taking Idelalisib at the time. But there are some similarities to what happens when Ibrutinib is stopped, which a researcher might find useful.
Wishing you all the best for your talks with doctors this week.
The damage that a medication can do when it is interrupted is incredible. Researchers want to find out why this is happening and to know why there are patients who get it and there are others who don't. They also want to know more about RT and how it behaves with Ibrutinib. There are hardly any cases like these and the doctors are enthusiastic.
This October 2019 paper from the State Key Laboratory of Experimental Hematology in China, illustrates a promising way to tell the difference between blood from healthy patients, patients with CLL and patients with DLBCL. I wonder if further research based on these findings, could result in the development of a non-invasive test to tell the difference between true Richter's Transformation and pseudo Richter's Transformation, when patients on CLL who go off Ibrutinib develop concerning symptoms? It's much easier, quicker and far less risky for the patient to analyse a blood test, than doing a PET scan to find a hot node and then performing a node biopsy. Less costly too. Please pass this on to Dr Elias Campo for his assessment.
Raman spectroscopy model can distinguish between CLL and DLBCL
Raman spectroscopy (RS) can provide fingerprint-type information on biochemical molecules.
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Most importantly, we found specific biomarkers for DLBCL compared with CLL by S-line analysis. From the S-line analysis, we found that the main spectral regions in the DLBCL and CLL models are similar but the 1445 and 1655 cm-1 peaks have different patterns in the two models. In the CLL samples, the shifts at both 1445 and 1655 cm-1 are not different from those in the HD samples. However, in the DLBCL samples, both the 1445 and 1655 cm-1 shifts are upregulated, which infers their potential as biomarkers for DLBCL.
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Our exploratory study primarily demonstrated the great potential of developing RS blood plasma analysis as a novel clinical tool for the noninvasive detection of DLBCL and CLL.
Dépistage des biomarqueurs par spectroscopie Raman en étudiant les caractéristiques des empreintes digitales de la leucémie lymphoïde chronique et du lymphome diffus à grandes cellules B
Cet article d'octobre 2019 du State Key Laboratory of Experimental Hematology in China, illustre un moyen prometteur de faire la différence entre le sang de patients en bonne santé, les patients atteints de LLC et les patients atteints de DLBCL. Je me demande si des recherches supplémentaires basées sur ces résultats pourraient aboutir au développement d'un test non invasif pour faire la différence entre la vraie transformation de Richter et la pseudo transformation de Richter, lorsque les patients sous LLC qui cessent d'ibrutinib développent des symptômes concernant? Il est beaucoup plus facile, plus rapide et beaucoup moins risqué pour le patient d'analyser un test sanguin, que de faire un PET scan pour trouver un nœud chaud, puis d'effectuer une biopsie du nœud. Moins cher aussi. Veuillez transmettre ceci au Dr Elias Campo pour son évaluation.
Le modèle de spectroscopie Raman peut faire la distinction entre CLL et DLBCL
La spectroscopie Raman (RS) peut fournir des informations de type empreinte digitale sur des molécules biochimiques.
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Plus important encore, nous avons trouvé des biomarqueurs spécifiques pour la DLBCL par rapport à la LLC par analyse en ligne S. À partir de l'analyse de la ligne S, nous avons constaté que les principales régions spectrales dans les modèles DLBCL et CLL sont similaires, mais les pics de 1445 et 1655 cm-1 ont des modèles différents dans les deux modèles. Dans les échantillons CLL, les décalages à 1445 et 1655 cm-1 ne sont pas différents de ceux des échantillons HD. Cependant, dans les échantillons DLBCL, les décalages de 1445 et 1655 cm-1 sont régulés à la hausse, ce qui en déduit leur potentiel en tant que biomarqueurs pour le DLBCL.
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Notre étude exploratoire a principalement démontré le grand potentiel du développement de l'analyse du plasma sanguin RS en tant que nouvel outil clinique pour la détection non invasive de la DLBCL et de la LLC.
Sorry for not answering you earlier, but I was out in the field for a week and I didn't have internet.
Tomorrow, Dr Elias Campo will pass on your information. He is excited about the investigation. They have my blood when I was ill with Leukemia, then the RT biopsies and now they have clean blood from treatments. The idea is to study my human genome and understand why it transforms when I stop treatment. Also if it is an open door to know how you can prevent leukemia from transforming into lymphoma.
Tomorrow I have a scan and analysis and on Wednesday results. I feel fine but you never know the surprises you may find. I plan to keep you informed of everything.
When I went to the hospital to donate my blood for a study, they told me that they had seen RT that went slowly but they had never seen an RT where no trace appeared after two months of the biopsy. The prognosis of life of a RT without treatment is four and a half months. I hope it was an Ibrutinib error. I feel fine. I pray that on Wednesday they tell me that my scanner is clean. What is certain is that there are already cases where the Pet comes out clean and in the biopsies RT comes out after a surgery and subsequent Biopsy. There are people who have been treated without having declared RT and now there are doctors who are not going to treat and monitor the patient to see if symptoms appear. On Wednesday I have a consultation and I am already nervous about the results. I feel fine and I can't find any lymph nodes. All this is crazy.
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Update for UK FLAIR Study Participants who have come to the end of 6 years of Ibrutininb treatment.
