After being on Ibrutinib for 8 months, my numbers are all back in the normal range. My oncologist refuses to say I'm in remission, and simply says that if I stop the Ibrutinib my numbers will go back up. However, when I sought a second opinion about 9 months ago, that oncologist said he would not be surprised to see me go into remission after 6 months of treatment. How does a person know if they are in remission and can stop treatment? What happens if I just stop the Ibrutinib without telling my oncologist? If my numbers go back up will starting back on the Ibrutinib lower my numbers again, or will it just stop working? Thanks for any thoughts.
How is "remission" defined for CLL?: After being... - CLL Support
How is "remission" defined for CLL?
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Living2
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hi Living2, I asked my hemotologist this question. I’m on acalabrutinib, I’ve been on it since November. She said that I will need to be on it until it stops working. She said that if I stop taking it my disease will progress and might even become aggressive. I was hoping (wishing) that after taking it for a long time, I can eventually stop taking it when I’m in remission. Unfortunately That’s not the case with BTKs.
Thanks for the information.
This is pretty much what I was told by my heme-onc, though in my case I’m on ibrutinib.
When first talking treatments she discussed BFR chemo as an option and for that she said most people get a remission of 3-5 years (if I am recalling correctly). But the CLL would likely come back. Ibrutinib meant taking a pill every day until such time as it stops working. (Variable by individual.)
I’ve been fortunate to have only minimal side effects. I’m hopeful the ibrutinib keeps on working and thankful it has worked as long as it has.
there are other combination drugs, like O and V or OVA and so on. These drugs are time limited. (2 years) if you become umrd negative you’re in remission and they stop the drugs.
I am a bit confused too. If its working & you can tolerate the side effects, why stop??? I would be scared to make my CLL more resistant. One person here I read was on Ibrutinib for 9yrs until it stopped working, that’s great without having to try anything else. And in that time, something better may be available for you🤷🏽♀️
Thanks for your thoughts.
Living 2, I think the definition of remission is a bit of a moving target which depends on who you talk to and in what context.
Some people on the forum taking ibrutinib have announced that their doctors have told them they are in remission. Since ibrutinib and other btk drugs rarely get people to mrd negativity, in that context I think remission simply means that their labs and wbc have returned to normal numbers. It doesn’t mean their cll is eradicated. My labs now while I am on acalabrutinib are mostly normal, although I don’t see myself in remission because I assume I still have Cll cells that will grow if i interrupt treatment.
The more technical definition of remission, typically used in clinical trials, is where both our blood and marrow is mrd negative or mrd undetectable. This means that based upon the most sensitive testing they have, no cll cells can be found in our blood or marrow.
MRD negativity is therefore the holy grail for some, that is, people want to be off cll meds and with undetectable cll. Venetoclax based treatments, and FCR for a lucky subject with good genetics, are more likely than btk drugs to get folks to mrd negativity.
It’s important to remember, though, that MRD negativity is no guarantee our cll wont return. The end game for many cll doctors for us is length of survival, not mrd negativity, which are different metrics.
I tried venetoclax to get to mrd negativity and for me, the side effects were too difficult. I never got there. Upon the advice of my doctor, I am now just on acalabrutinib again. Will those who get to an mrd negative remission outlive me with my Cll being controlled indefinitely with acalabrutinib and me never reaching an mrd negative remission? It’s a good question, and I don’t think anyone knows the answer. Some FCR remissions have been very durable, its unknown how durable venetoclax remissions will be.
Thats all a long way of saying that remission with cll can mean different things. Remission is not necessarily the end game for everyone with cll. Survival might be more important. And for some folks on btk drugs that mange cll, not eradicate it, they might live as long or longer than those who achieve remission with long term cll control. Some may do better with venetoclax remissions, no one knows for sure, thats why we have treatment choices.
Thats all my lay understanding and I could easily misunderstand these things. I dont know that cll will ever have a one size fits all treatment.
Cajunjeff and Living2,
Skyshark has provided references to the iwCLL guideline definitions of Complete and Partial remissions, etc., above: healthunlocked.com/cllsuppo... but as Cajunjeff covers, these are for treatments which try to totally eliminate the CLL, so the definitions were based on what older chemoimmunotherapy treatments tried to achieve.
Likewise, the NCCN Patient Guidelines, used in the USA and from which the iwCLL guidelines were developed for international use, defines the different outcome categories from treatment per the extract below; nccn.org/patients/guideline... defines these in the section;
Checking treatment results
You will need to have tests to assess treatment results. These tests include an updated medical history and physical exam, blood work, and sometimes imaging. There are four types of treatment results based on these tests:
* Complete remission is the best result.
With a complete remission, enlarged organs and lymph nodes are back to normal size. You have no leukemia symptoms like fever. Blood counts are within normal range. No leukemia cells are detected in the bone marrow with common tests.
* Partial remission is a good result.
Enlarged organs and nodes have shrunk to less than half their size. Blood counts are returning to normal.
* Stable disease is less than a partial remission. The cancer is not getting worse.
* Progressive disease is a worsening of the cancer.
Cajunjeff, as you note, in clinical trials Minimal Residual Disease is also evaluated, but specialists can request this testing for people not on clinical trials.
Living2, you are unlikely to achieve a remission on ibrutinib in under a year; it takes at least a year for the new combination treatments (nearly always including venetoclax) to usually achieve complete remissions. BTK inhibitors like ibrutinib take many years to get there - in fact, as Cajunjeff covers, with these drugs, the goal is to keep your CLL under control. You may do better survival wise by avoiding the higher risks of infection, etc, that can occur with faster acting treatments. Some people never get to normal lymphocyte numbers on BTK treatments, but the CLL lymphocytes in the blood are dormant and provided you have good enough counts of platelets, haemoglobin and neutrophils, etc., and your spleen and nodes are near enough to normal, it doesn't really matter. However, if you stop taking ibrutinib or other BTKi drugs, your CLL can sometimes quickly return in what's called a Tumour Flare, in which case resuming treatment will eventually get you back to where you were - provided that by stopping and starting treatment, you don't cause your CLL to become resistant. This is because ibrutinib is an inhibitor drug; it inhibits CLL cells from dividing, which is when errors in the DNA division process can occur. If the DNA error results in a CLL sub-clone resistant to ibrutinib, it will continue dividing and your CLL will no longer be controlled. Unfortunately, there doesn't yet seem to be much in the way of guidance of who can safely stop taking BTK drugs after they've achieved a remission, though generally, you'd expect that it would be more likely if you had good markers.
Neil
Thank you Neil. Your explanations are always educational and I value them greatly.
BMB and PET scan were used to confirm my MRD.
I take Acalabrutinib and at my last check all was stable and my numbers within normal ranges. My consultant said she would consider me in a good partial remission. Full remission not possible because if I stop taking the treatment, my numbers would increase again.
Ask for a uMRD (min residual detectable disease) test as a 1st step.
You would risk a flare up and even a spleen rupture. It happened to others on this forum.
cancer.gov/about-cancer/dia....
Cure means that there are no traces of your cancer after treatment and the cancer will never come back.
That's rare in CLL, a chronic cancer.
Remission means that the signs and symptoms of your cancer are reduced. Remission can be partial or complete. In a complete remission, all signs and symptoms of cancer have disappeared.
By this definition, a complete remission would mean maintaining uMRD, all blood values in normal range, and no CLL-associated symptoms. With BTKi monotherapy this might be achievable for a minority of patients. But is it worth getting hung up on definitions?
The patient and physician, with lab support, can gauge how well the treatment is working and when it's time to try something different. Also, the "best" treatment may put the patient into remission, but what use is that if the treatment can't be tolerated?
It's rare indeed but the data for V+O in particular (especially in younger patients) is really promising, with a number of people at MRD- 5 years later.
It remains to be seen, but a good percentage of as yet untreated CLL patients with the most favourable markers might need only one time-limited course of treatment, as has been the case for roughly half of FCR-treated patients with IGHV mutated, 13q del CLL. In the latter case CLL specialists speak in terms of cure hematologyandoncology.net/a...
Yup, that's what my specialist keeps saying! I'm 13q but also Trisomy 12, yet he still thinks I might have a chance at a cure.
I am in remission on Calquence but have to continue taking the drug ad infinitum. The drug keeps you alive whatever’it is so be thankful you are still here
Hi Living2, I too have an interest in how remission is defined having recently been told I am in remission, this after 10 years on Ibrutinib and 11 years of regular IVIG infusions.
My specific blood tests (UK values) which are continually High or Low taken on 28/04/23 are:-
Platelets (low) 122
Chloride (high) 110
Creatinine (high) 109
EGFR CKD-EP (low) 57
Phosphate (low) 0.63
Serum IgM (low) 0.2
Serum IgA (low) 0.35
All my other blood results are average around the lower end of normal accept for my Serum IgG which was 10.1 at my last blood test which was just 13 days after my regular 3 weekly infusion which has gradually improved from less than 5 during the pandemic lockdown when I missed 2 infusions.
I don’t know if any of this is of value to yourself but I would be keen to know if this indeed confirms I am in remission.
My best wishes
Aerobobcat
Hi Aerobobcat,
If you look back at earlier posts, you'll see that the only relevant result from what you've provided is your platelet count. If you meet the other remission criteria, on the basis of your low, out of reference range platelet result, you have achieved a partial remission "Blood counts are returning to normal". where you have plenty of good company.
Neil
Thanks Neil, that has given me some hope that I might be able to reduce my Ibrutinib dose to try and reduce the side affects I continue to suffer.My regards
Hi, I've been on ibrutinib for 5 years, like you I responded well to the medication and saw normal blood results within the first 6 months. However I experienced some pretty severe side effects so I reduced the dose to 280mg per day which gave a small degree of relief and then went on to to reduce to 140mg which made a big difference. 4 years later I've seen no negative effects on my bloods. Consultants are generally very reluctant to sanction deviation from the recommended prescribing (and that's a discussion for another time), as was the case for me, so you may just have to take your own decision on this as I did. There are plenty of ibrutinib patients doing very well on a reduced dose and no doubt you are getting regular blood checks so you can monitor the situation as you go. As for stopping completely I doubt that would be a good idea, most likely you'd find that the CLL would creep back and be potentially more resistant to the ibrutinib.
Good luck.
Mike.
Hi Redlion, did you have any difficulty getting a reduction in Ibrutinib dose? I’ve been trying to get a reduction from my 280mg but my haematologist is not so keen. All I know is I’m really struggling with my mobility and in constant joint and muscle pain together with many other issues.
My regards
Aerobobcat
Aerobobcat and Redline, I had immediate bad side effects from the full dose of Ibrutinib but also spectacularly good results.I received a reduction to 170 and things improved but I still had side effects as well as good results. After about 9 months with my numbers close to normal I requested to go off the drug and my doctor agreed. It's been over a year now and my numbers have been increasing but very slowly. They are still well below what they were during much of my watch and wait phase which lasted almost 10 years. If I ever need to go. back on the drug I will try the 70mg lowest dose first. Some people, especially older people, react strongly to drugs. My doctor said I was "exquisitely sensitive" to the Ibuternib. I understand that because of cost issues some patients even go on and off the drug regularly and do well. So I think sometimes you as the patient need to just assert what you want. Of course there's a risk but CLL in general is not a killer disease.
Hi 22011, many thanks for your response and your own experience with Ibrutinib. Yes, I too managed to get a break from Ibrutinib early on in my treatment, this was because it was making my pre-existing symptoms of my Behcets syndrome more difficult to deal with.
However, they only agreed because I wanted to stop the treatment altogether that was at the beginning 10 years ago.
Since then I have been suffering so much more with joint pain and upper and lower limb Neuropathy without any relief.
I now have a date for spinal nerve denervation so I am hoping that this may make life more tolerable.
My regards
Aerobobcat
Hi,After repeatedly trying to get my haematologist to engage with reduce dosing without success and researching the issue I decided to take matters into my own hands and just did it. After 6 months with no adverse effects on bloods I advised him of the situation at which point it was difficult for him to not agree with me. My body my choice. One of the issues I had was also with joint pain and arthralgia which was largely resolved by going to 140mg/day.
Cheers.
Hi Redlion, thanks for your response which has similarities to my own experience. Due to a pre-existing condition and the difficulties I had with chemotherapy I was put forward for the Ibrutinib trial at the Royal Marsden hospital.
During the early months I suffered more with the side effects and asked for the treatment to be stopped. In truth I had such a difficult time with treatment, 15 hospital admissions with Pneumonia and Sepsis on 4 occasions.
However, I was advised to have a break from treatment and then gradually increased doses of Ibrutinib finally settling on 280mg.
At the present time I’m awaiting the Haematologists decision to try a reduced dose, so time will tell.
My regards
Aerobobcat
That's a good thought Mike. I'm definitely going to discuss reducing my dosage with mu oncologist. Thanks again.
That is a very insightful notion. I too had bad side effects on full dose of Zanubrutinib so I switched to Acalabrutinib 1/2 dose & its been 30days. I see a new Onc 6/19 & hopefully we can reason together. All I know is ending up in a crowded diseased filled ER can not be on the agenda🤦🏽♀️ PERIOD!!!
I agree that remission means different things to different people. Technically I am not in remission. I took Ibrutinib and Venetoclax for 2 years and did not achieve uMRD status. Like Redlion above, I have now been on Ibrutinib alone for almost 4 years, but at the lowest dose of 140 mg. It is controlling the disease very well. If you are really worried? I would ask my doctor about the possibility of lowering the dosage.
Conferring with my specialist and observing the definitions, I have interpreted remission for my circumstance to be the point at which I am confirmed MRD negative with no progressive disease at a measure reached after being treated rather than after stopping treatment.
The remission after stopping treatment would be considered a continued remission.
I was told by a prominent research manager in 2019 that the research community was given approval to use the term MRD negative as a measure in defining remission. I do not however remember the entity that granted approval.
Living2 -
Numbers going back up may depend on your markers and other factors yet to be discovered.
There's no protocol for stopping BTKi monotherapy yet. The combo treatments in trials do flow cytometry, and often, bone marrow biopsy as well to establish MRD levels.
But the pandemic has forced a few people to go off therapy while on Paxlovid, and some of those did not go back on. I'm hearing anecdotes in other forums about this. I think that the cases I hear about are either tied to COVID treatment or after BTKi side effects, and the doctor deciding to wait and see if numbers rise.
A previous HU post:
healthunlocked.com/cllsuppo...
I would think that agreeing with your doctor on timing a drug holiday to start before a regular blood test for comparison to previous tests would be good.
Also, I'm not clear on the thinking regarding CLL rebound after a drug holiday being more harmful. Is there evidence that such a rebound leads to new B-cell mutations or more aggressive disease, or is that just hypothetical?
=seymour=
maybe Neil, can answer your last question? Neil? 🙂
Treatments select for sub-clones that are resistant to the drug. Inhibitor treatments inhibit CLL from dividing, so theoretically after stopping treatment with a BTK, the mix of CLL sub-clones is more likely to include some with resistance to a BTKi. You'd find that out on recommencing treatment if your CLL didn't respond as well as the first time. Some members have reported that happening, but might it have happened anyway? So I'd say hypothetical and difficult to prove until you did a Randomised Clinical Trial for early stage CLL to see if there was any statistically significant difference in the development of BTKi resistance over time. You'd expect some difference, but how much?
Neil
I appreciate it, thanks Neil
The proof of existence of subclones is possible with clone sequencing tests, like ClonoSEQ. While they only count the raw numbers of different clones, and not the actual resistance mutations, I think they can see whether new clones developed during or after treatment. ClonoSEQ is being used in more trials in the US,and some patients even request it. It's best to do it both before and after treatment. The trial I am in is also doing it once during treatment.
I believe I saw a paper on another sequencing method to identify unique clones that was done in the UK ir EU, but I got the sense that it is not yet a standard.
=seymour=
Good question. At the end of my 12 month O+V treatment regimen, my FISH test came back with comments "There is no evidence of residual abnormal B-cells...no abnormal blast population identified." I asked my oncologist, "Does this mean that I'm in remission?" He replied, "Yes." I asked how long I can expect to be in remission and he indicated that it varies patient to patient. However, he did say that O+V is still a fairly new protocol and 2 to 5 years, or maybe longer, as more patients are in remission longer and longer. I read somewhere that roughly 80% of patients are in remission 5 years out. My mother died of Lymphoma at age 78 20 years ago. If she were alive today, I bet she would be able to live many more years with the disease. Also, I believe that AI is going to put medical research on steroids and amazing treatments are coming down the pike.
I agree. We have a chronic illness/disease and when our numbers get better we stay in a maintenance state with the medication. It took a while for me to accept that. I continue to live in one day at a time and embrace the present moment. I will be 70 this year and continue to work P/T to keep busy and not fixate on it. It helps that I enjoy my work!!!
I think of it this way (informed by conversations on this topic with my CLL specialist):
CLL is at its core a disease of the bone marrow - where your blood is constantly remanufactured as older blood components are removed from your body. It's easy to fixate on counts like ALC because they are a single number, inexpensively gathered, that gives you a rough idea of where you are at. But they're not the cancer; the cancer is in your bone marrow.
Beating your blood counts down to normal levels is a great sign; it means that your rate of bad lymphocyte creation etc. are low. But it does not mean your cancer is eliminated from your bone marrow.
I think of this as "moving the battlefield". Early on, the signs of progress are in your blood and easily seen. But as the battle moves more directly into your bone marrow, in effect battling the last 20% or whatever of bad bone marrow cells, the signs are more localized.
My counts got to near-normal 4 or 5 months into treatment in my combination trial with fixed duration drugs. But when asking "how much longer", the answer was very clearly "at least another 6 months and likely longer".
At some point I hope to reach uMRD, and then they will do a confirmatory bone marrow exam to confirm. But until then, the battle is not over, it's just in quieter and darker places.
I can relate to your analogy. Because having CLL Leukemia 13yrs 8mos without treatment then hitting stage 4 & needing treatment. So you fight with the basics by following the 8 Laws of Health, then as certain numbers change you add supplements to combat/normalize them, you maintain Covid/RSV/Flu Protocols at all times & pace yourself. Now on treatment I must remember to be grateful that I am still alive & see what side effects needs to be addressed or how much energy I have for the day’s chores🤷🏽♀️ I really try to focus on all the good because I seen my death when I hit stage 4/got Covid Pneumonia & the Lungs Collapsing recently after starting treatment. There is so much good, my hair & nails are growing more on therapy. My appetite is less, responsibilities less & I have a permanent excuse to be late or not show up at all lol. CLL Leukemia will never take my humor away 🤣😂😆🥰
The 8 Laws of Health
Always follow doctors orders , I am in complete remission was on venetoclax for 2 years all numbers now normal for 6 months, for the last year no cancer cells detected in bone marrow , but the treatment was 2 years and thats what I followed.Now I go back in 6 months for followup,maybe your doctor could communicate a little better, good luck , 2 years ago I was on deaths door but had the best hematology team in the world, I am proud of them and grateful.
Living2 -
I am in an aggressive fixed duration, triple combo trial of pirtobrutinib, obinutuzumab, and veneteclax. They Monitor my progression with ClonoSEQ in blood and bone marrow, CT scans, and the usual CBC and Differential plus flow cytometry at intervals.
Their goal is to achieve uMRD6 in 7 to 9 cycles. A CT at end of Cycle 1 found that the node on my face shrank from 5cm to 2cm. Last week, I had a neck and brain MRI due to some neuropathy in one hand and the other side of my face. It saw the original node on my face as still 2cm.
So I asked my doctor if it's possible to be uMRD6 yet still have a node larger than the iwCLL Complete Remission standard of no nodes >= 1.5cm.He saud yes. So I could be technically in Partial Remission, yet uMRD. He said that uMRD is what counts in such a case. This odd possibility will remain until the iwCLL standard is updated to reflect current practice. It was last updated 5 years ago in 2018. Things are changing rapidly in treatment of CLL.
=seymour=
I stopped whilst I was in hospital with covid and my white blood cell went up and I became very I’ll so the hospital put me back on my meds which put my levels back in line again.
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