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CLL Support Association
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Potential cure for CLL

Has anyone followed the research in the UK in the Clarity and Flair trials that are underway. They are looking at the venetoclax and ibrutinib as a combined therapy. The Clarity trial took 50 patients, some in the final stages of the disease and mutations. They had a 100% response with 30% showing undetectable CLL in six months of treatment. Flair is now taking the trial to patients who have not received previous treatment. Some are using the word "potential cure", but as CLL is so slow to progress, it will be 10 years until we know. There is an easy to read BBC article here bbc.co.uk/news/stories-4292...

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that article was dated february 2018. Lots of new stuff and reports since then

One ongoing trial gazyva,imbruvica,venetolax. looks promising(and expensive)

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Meds are very expensive but free if on clinical trial.

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There are many people here in the UK on the Flair trail...do you have CLL? Usually it is polite to introduce yourself first...I see you just joined a few days ago.

Your title is misleading as well....we are still far from a cure considering CLL is a section of your DNA deleted....so, really, if you think about it...how is that DNA going to be majically restored?

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why such a harsh reply to someone who is trying to share what he/she thinks is good news?

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It was not meant to be harsh....I did that last week...I will keep working it on then....I just question any new users who starts posting things with Titles like this one....clearly an intelligent person.....has facts, figures and links....

But again, I question any user who joins in the last few days or month, never says anything...then posts something like this...

Again, I will work on handling it better

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Actually the title was lifted from the BBC Article. I think everyone here is smart enough to know the facts after reading the article. CLL is genetic switch that goes wrong sometime In your lifetime. Just like other cancers, taking out those faulty cells and restoring a base line is critical. As with all CLL patients, we have bad cells and good cells. If we can kill all the bad cells then, for me that is a cure. I’m going to stick with my positive thinking....

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This has nothing to do with positive thinking or negative thinking...this has to do with how normal humans generally socialize both in real life and online.....they exchange personal information, form bonds with some, but not all the other people....then participate in various discussions.

You never said a word before offering a fairly technical paper that you clearly seem to understand....but show a lack of awareness that there a tons of people here on the Flair trial....doesn't that seem just a little strange to you....well it did to me

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Leave it alone. We are all on this journey

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Give him a break lad

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Boy you are very full of yourself ! I am a new member also and I might post or not post but was not aware your approval was necessary

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My approval is not necessary but I am sorry to say, I never bothered to join the politically correct club.

But again, my real issue is people do not join a forum (or real life club) then the first thing they say is not about them...but about some "miracle cure" Humans simply do not behave that way....they generally try to exchange personal information not technical data.

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Good morning, Scottxxoo. I have never heard CLL described as part of our dna being deleted. Could you elaborate a bit more on this? Thank you.

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DNA is locked deep in the cells. Maybe he means RNA when the cell divides. Or confused with p17 deletion etc...Bloods are a science so it’s easy to get confused.

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Thank you, rockas!

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No I am, not confused, you seem to have some facts a little off...the nuclear DNA is deep inside the cells, of course...but the Mitochondrial DNA is out side the cells....not in the nucleus you are again, offering only part of the information.

Second 17p is considered more aggressive than 13Q or T12 but it is again, a deletion of a section of the chromosome which is really, just a deletion of the DNA chain itself. The only huge difference, and it is not that huge (i think) is 17p is a deletion on the short arm of the Chromosome...not the long arm

Blood science is a little bit like flying.....there is nothing really all that hard about it....but there is so very very much to learn that for most people, well it seems hard. I learned to fly when I was 16 and I learned about blood cancer when was skinny lad....didn't know know good from bad....oh wait...that from this....

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Scott but not everyone with CLL has a deletion of some type, do they?

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No, in the case of Trisomy 12 that is the addition of an extra 12 Chromosome....and FISH normal means the regular run of the mill suspects (11Q, T12, 13Q and 17p) are not the culprits so it is left unknown....it might be a deletion, might be an addition....or even a translocation....some part of this gene on this chromosome decides to move to another chromosome....I think Mantle Cell Lymphoma is a translocation....

As I said, this is extremely complicated science, with many many causes that all basically end up with CLL or something like it. Like getting run over by a train or a piano dropping on your head....the end result is pretty much the same even if the cause is different.....

Maybe I should of used a different analogy....but you get the idea...

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No I mean DNA, not RNA. Our Chromosomes are lengths of DNA....the Chromosomes only "appear" for lack of a better word when the cell divides.

In my case, I am 13Q deleted...that means a section of the 13 Chromosome (Q=Long Arm) is simply gone, deleted.....this can be between 50KB an 2.5 MB in terms of size (if I recall what I rad two years ago correctly).

But Tristomy 12 is actually an extra chromosome....not a deletion....Tri=3...so instead of 46 Chromosomes a person with Trisomy 12 has 47.

RNA does all kinda of things....there is all kinds, mRNA is messenger, tRNA is transcription.....but RNA is only 1 strand of DNA....

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Thank you for the explanation, Scott. So the 13Q is the marker that is most favorable, if I understand correctly? I don’t have any markers. I have CLL without any markers. However, I do have borderline Zappa-70, but the results indicate it is neither positive or negative. I find that worrisome...like...when are the markers going to materialize? When is the sky going to fall? So my CLL doctor says I am in the middle of the road. W&W, with intermediate risks, and he predicts I’ll have 10 years before treatment is needed. I was diagnosed October 2017, and since my initial diagnosis...my labs have improved. But...we just never know.

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13q del is indeed the most favourable marker. FISH testing only checks for a few of the many possible CLL cell DNA changes. If the changes in your clonal B-lymphocytes that resulted in them becoming CLL cells can't be identified by FISH testing, you are said to have a "Normal karyotype". Now it obviously isn't normal, or you wouldn't have CLL. A better description would be "None of the common DNA changes found".

Neil

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Thank you, AussieNeil. Your comment clears it up for me.

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Yes, I never heard this either and am interested to understand. Our blood has changed due to WBC and RBC but DNA?

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The Blood cells have changed due to a deletion/addition of the Chromosome(s). The high WBC count and ANC (Absolute Neutrophils) are a symptom of what is going on.....the B cells are defined as cancer because they multiply out of control and do not die (Apoptosis) so more and more the cancerous B cells fill your blood stream crowding out the other normal good cells....

All this stuff involved all kinds of genes and pathways (BTK, BCR, JAK2, STAT, etc etc) and not even the really smart people (of which I am not one of) understand the how and why of all of this.....

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Still unclear about the DNA part but thanks for responding.

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To to think of it simple.....if you take the entire 3 billion base pairs of the DNA double Helix and chop it into 46 sections.....now you have 46 Chromosomes....it is not exactly like that...but close enough. A deletion from a chromosome is the same thing as a deletion from DNA

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Is there anyone here on Flair I+V? They offered me that trial but since my symptoms has subsided and my bloods have returned to normal (well lymphocytes are still 25) I was moved to watch and wait. I would be interested to here about the trial and in particular those on I+V.

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Hi rockas and welcome.

Are you personally affected by CLL or just reporting this as an item of interest?

The Clarity and now Flair trials are well known to U.K. members on here and I’m on the I&V arm of Flair. The CLLSA had the superb Professor Hillmen to speak at a conference in Leeds on the success and promise offered by this combination. This video shows him describing the outcome. Of course we await with interest the outcome of Flair in the fullness of time but it’s certainly true that there are some further promising combination therapies out there which give us all hope.

Tell us about yourself and it would be better if you restricted your post to the community.

Best wishes,

Newdawn

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I was diagnosed in Feb this year after contracting a nasty virus. I’m 47 and currently on watch and wait as my bloods have remarkably improved since I was diagnosed.

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Hope you remain stable for a very long time rockas but as you can see, there are some very promising therapies out there now should you ever need to use them!

Regards,

Newdawn

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Thank you very interesting.

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Some doctors are starting to use “possible cure”, especially related to patients who reach -MRD status. As you say, it will be years down the road before there is definitive proof of a cure, but a very long remission without symptoms sounds good in the meantime.

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Although now I believe my doc means MRD or a deep remission that will likely last longer than my lifespan - I know my doc feels that we are getting very close to a cure with newest meds.

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Agreed. We are all going to die of something most people don’t know when or how, I guess we all know how.....just not when. For me it’s about living long enough to see my son grow up and stand on his own two feet. So 10 years of remission for me would be great, 20 years would be amazing and any longer I’m into old age and all the other risk associated with that. So maybe there is never a cure but living a long good quality of life is a close enough to a cure for me.

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I believe this is the answer.

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🤞

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I am on the Acalabrutinib, Obinutuzumab, and Venetoclax trial in the U.S. at the Dana-Faber Cancer Institute. Just short of my seventh month in the trial, I went MRD-. No one is talking about a cure from this trial. There is no science to back up that claim. We know that some people with non-complex CLL achieved remissions without endpoints after treatment with FCR. Those are starting to look like cures. But, this combination treatment is very safe and tolerable. I expect at least two years with no signs of progression after discontinuing all drugs after fifteen months. Anything more will be a pleasant surprise. If I do progress, the same drugs may hold CLL at bay. The thinking is to knock it down quickly with enough complexity that the chance for mutation is minimized. So, maybe I get another knock down. By then, amazing new treatments will be out of the pipeline. Or, maybe my remission will be long and durable. We, now, are the ones who will help bring about a cure by participating in clinical trials, which is, for many of us, where the best life-prolonging treatments are to be found.

Lastly, it is known that for many people, CLL can be a manageable chronic disease. So, the good news is, whether we are “hopping lily pads” from one treatment to the next or treating CLL as a chronic condition, there is great reason for hope.

Glenn

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When did you change your nick? Add sweeeeeet on going MRD....

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I changed my nickname when I started to see the real possibility of MRD negativity approaching more quickly than I had anticipated. Those results left me confident that my “worst case scenario” is that I will be “hopping” from good treatment to more sophisticated treatment to get through this “swamp” of CLL to a reasonably long lifespan.

Thanks, Scott! Now I just need to stop needing the Neulasta shots. They hit me hard for five days.

Glenn

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I had one of those shots yesterday. I agree they can hit hard. I never knew what bone ache was until last evening. Not fun.

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Hope - Has your doctor or nurse mentioned taking Claritin for the bone pain? It doesn’t help everyone, but makes a huge difference for some. It’s worth asking about it. Don’t just try it on your own , as there could be issues related to drug interactions.

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Yes helps me.

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Hello:

No it wasn’t mentioned to me but a couple of Advil numbed the pain and let me sleep. Today the pain is much improved. I had 2-3 of these shots after my chemo treatments last year and interestingly I never had bone pain. Fortunately, I read about bone pain on the forum previously so I wasn’t concerned last evening. Had I not read about this potential side effect I would have been very concerned. I appreciate the tip on Claritin. I’ll ask about it next time.

Thank You!

Mark

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Perfect answer and my thoughts exactly 💙

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My doctors at Froedtert in Milwaukee WI, have whispered the word cure. I love that attitude even if it's a little early. Thanks for sharing.

J.

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My last Hematolgoist used to tell me I would live forever...and I loved hearing it...but you know...after leaving her office found it hard to keep believing ...

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I went through a seemingly long period of time when I was depressed and stressed but then I started a new plan. I started believing that this problem wasn't going to beat me. Now I found out I have at least one spot of Melanoma. It still will not beat me. I believe in my future. And believe it or not, I'm a happy man because of it. I feel really bad about Chris, but I think somewhere along the line, he came to that same conclusion. He always seemed so upbeat, it was hard to believe he had gone through everything he had. Take care my friend.

J.

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Hi Scott, I hope I dont get my head chewed off but you are not your usual funny self. I think I can guess why. When someone you care about passes away it is so sad and changes our perspective on life. Iv been affected by it too. Anne

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I still do not understand the mantra that CLL is an incurable disease. It’s not. Some people who get stem cell transplants are thought to be cured.

Also, a very significant number of mutated Cll patients who received FCR have had no evidence of disease 20 years out. If you had a twenty year remission with most any other cancer, you would be considered cured.

For those that do have twenty year remissions with FCR, most achieved mrd negative status fairly quickly. How fast someone gets to mrd negativity is therefore an important predictor of who will have long, most likely permanent, remisssions.

A lot of people taking ibrutinib plus venetoclax are getting early and deep mrd negative remissions. That’s why some doctors think an ibrutinib venetoclax combination could be curative. How many will be in remissions in twenty years? Well we will not know until twenty years have passed. What we do know nowfrom ibrutinb/venetoclax clinical trials is that the combination gets some folks mrd negative very fats, the most important predictor in FCR trials for a deep and long remission.

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If CLL is only a treatable disease or a curable disease is a topic that is way way way above my pay grade, in truth. This is such a complicated disease involving things the smart people can't understand even.....

And then of course we get the philosophic discussion....if we make it go away and it never returns is that being cured, or just permanent control.....do we need the deleted/added sections of our genetic structure repaired to be "cured" or just make the cancer cells go away....I really can't answer that. Personally though I would not think cured, but rather controlled....

But that might be incorrect thinking....we get chickin pox....and our body fights it off and we think we are "cured from that virus" but really it is just controlled by our immune system....the virus is still inside us....

So I don't have an answer to that question cure vs treated....

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I have good reason to fully embrace the hope that I&V will be curative being on that combo and it would be fantastic to reach MRD for a fair number of years, preferably forever! I think this feels different dependent on age and if I was 30 or 40, it probably wouldn’t feel quite so ‘curative’. Getting near to natural longevity is my aim and I know they’ll be a price to pay in many ways. I’m still very thankful to have that chance however and have already had a second CLL related cancer and some near misses with sepsis.

However the treatment can exact a high price for many of us too. The risks exist and not an insignificant number of people become refractory to Ibrutinib or have to cease due to cardiac/bleeding and other issues.

As the immune system rests on two major pillars: the innate, general defence and the adaptive, specialised defence, I’m not sure I could feel cured living out the rest of my life with Hypogammaglobulinemia. The damage has been done and my immune system is essentially severely damaged even if/when the CLL cells are removed. BTK’s don’t fully restore that antibody function.

However, with the invaluable benefit of IVIG, I’d live gratefully with that knowing the malignancy had been eradicated.

This is an interesting discussion looking at the yay and nay side of this debate;

ashclinicalnews.org/feature...

Regards,

Newdawn

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I am very curious about this I+V combo as I was just told in the last hour that I need to start treatment. If one gets to MRD remission quickly, do they keep taking the drug? How long is normal to take the drugs?

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That’s what they are trying to figure out with all the different clinical trials going on with this combination, so the answer to your question depends on the protocol of the trial and how the trial is designed. A typical ibrutinib/venetoclax trial might have someone starting on ibrutinib to reduce disease burden as to reduce the risk of tumor lysis when venetoclax is added.

In some trials they might have one arm stop all therapy at mrd negativity and the other arm continue with ibrutinib maintenance therapy.

I do think the hope is people will be able to have long periods of remission without taking any drugs. We do not know the impact of long term use with ibrutinib or venetoclax, but there is reason to worry that there might be some unfavorable event with long term use.

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Where you are in the world will have something to do with which treatments are available to you. If you are in an I+v trial, the design of the trial will control whether you stay on the drugs long term or stop at some point, usually upon reaching MRD status or very close to it. If your doctor prescribes the combination “off label” ( the combination not yet FDA approved) it would be up to the doctor which way to go, with your input of course, but something new will probably come along before that decision is an issue.

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Hi again. Mr. Killjoy here. Here's a link to an OncLive that coincidently came out today. It is with Dr. Matthew Davids at the Dana-Farber Cancer Institute in Boston. He is also my doctor. He discussed "cure" in the context of one- and two-drug protocols, including in the CAPTIVATE, FLAIR, and DUO trials. He mentions nothing of the the three-drug trial (Acalabrutinib/Obinutuzumab/Venetoclax) I'm in.

onclive.com/web-exclusives/...

In this OncLive article, a panel discusses the following trials: iLLUMINATE, Alliance A041202, and ECOG E1912

onclive.com/publications/On...

Glenn

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Thank you for sharing. Knowledge is power.

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Hmm, I was interested to read Dr. Matthews take on CLARITY, however somewhat disappointed as I can’t find comment on it in the text of the discussion at all. AmI missing something?

Speaking as a CLARITY participant I always become focused when someone mentions it.

Gave I missed something in the referenced text?

best, rob

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Hi Rob. With apologies, I was fairly exhausted when I added that post. Still am, but I think I corrected it. I had been reading about CLARITY somewhere, but not in the article I referenced. I have changed my post to be more accurate. Sorry for the confuse. How are you coming along?

Glenn

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The Captivate trial in the USA is showing very good results as well,

Be well,

Hoffy

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Thank you for sharing this article. It brings me some relief and hope.

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