I have been on Ibrutinib a little over a year now Male currently 49 yrs. old my WBC count was as high as 350k now hovering at 85k. I am now on my second oncologist first one was adamant about FCR which I refused since I wanted a chemo free treatement. I have read so much about the new combination Venetoclax and Ibrutinib placing patients into MRD negative status, that I am anxious to try this to get my WBC count down to normal. My new Oncologist seems happy with where I am and doesn’t want to take any chances on adding something new. I live in Maryland and was thinking about making an appointment to the University of Maryland UMGCCC Center. I just don’t want to go to another Center if I am going to hear the same advice. Your thoughts and would love to hear from anyone who is currently on the combination treatment. Thanks!
Ibrutinib Partial Response: I have been on... - CLL Support
Ibrutinib Partial Response
I think adding venetoclax to ibrutinib is the future for Cll treatment. I don’t know that you can do it very easily outside of a trial though. There might be a hurdle getting your insurer or Medicare to pay for a second super expensive drug when the first is working.
I think there are a lot of specialists that would agree adding venetoclax is a great idea. It’s worth trying. The harder part, outside of a trial, might be getting the insurer to pay.
That could change if venetoclax gets broader approval. I think that will happen before long.
It’s difficult to know what your haematologist’s objection is since I&V is showing remarkable success as a ‘kill them off and clear them out’ combo!
I was lucky enough to get the I&V arm of the Flair trial but can’t give any feedback as I’m only 8 days in and keeping fingers firmly crossed.
I’d urge you to seek that second opinion and if there’s clinical reasons why Venetoclax shouldn’t be added, they’ll tell you. However, it could be what you need at this stage if it’s available and fundable.
Just to add, Venetoclax needs careful monitoring due to the risks of Tumour Lysis Syndrome so you may require overnight hospital monitoring as it’s ramped up.
Best wishes,
Newdawn
When I saw Dr Peter Hillmen in around August 2018 he was clear that at that point he did not believe there was yet enough evidence to use I plus V outside of a clinical trial, even if someone had deep pockets and could pay for both. And of course he is a strong advocate for that as a future option pioneering it in Clarity and Flair. I guess he was saying it’s just a bit too soon. Studies like Flair will help determine what the best treatment combinations are.
I have heard of a few American members being given the combination of V plus I outside of a trial already. But not many.
I suspect we are going to see an explosion of new studies in the coming years coming up for not just venetoclax but other drugs to be added to someone who is doing reasonably well on Ibrutinib to see if the addition will improve things.
Another option is to at some point simply switch from ibrutinib to venetoclax. When to judge the right time to do that in an individual case is likely to be far from an easy decision. These kind of decisions are going to only get harder as we get more options available to us and really to me provide more force if more was needed to the argument that we need the treatment of CLL to be concentrated in the hands of fewer real expert teams who can then develop lots of experience and hence clinical feel of what is the best thing to do for patients.
As you are in the USA you might also want to try the CLL society second opinions over the web if your insurance won’t fund one.
Agree to a point Adrian but at this stage it sounds like Litevibe would benefit from a second opinion anyway because there may be other combinations that would move him further towards MRD/CR and have the facilities and expertise to introduce them.
I added the careful monitoring because not all sites will be up to speed on the use of these drugs and it may explain his present haematologist’s reluctance to try Venetoclax.
Even outside of a trial, the medical oversight should be equal and the medical attention and monitoring comparable.
Newdawn
There is debate as to how important MRD negativity actually is. If we think of CLL like a racing car zooming, if ibrutinib can put the breaks on and even turn it into reverse does it actually matter if it doesn’t destroy it totally?
Does a partial response make clonal evolution and the emergence of mutations more or less likely than intermittent aggressive treatment? If the only cells that are left behind are mutated and aggressive will they grow back quicker than if a few more benign cells are left still around?
Only clinical trials will demonstrate this.
One CLL specialist expressed to me that he has a hunch that MRD negativity may be important early in the disease in order to get the most complete remission and recovery, but perhaps not so much later on.
Perhaps we will all end just accepting that we can’t abolish this disease and need to create an environment in our bodies where we can live together with our cll better?
And perhaps that is what ibrutinib is about philosophically. Is it possible that by being in at least one sense more “gentle” on the disease that it may be more “gentle” with us in return? Could that explain the great results we see in ibrutinib studies despite so few getting to MRD negativity?
There are so many mysteries. So many unanswered and at the moment unanswerable questions.
Flair will help. We have in FCR what is now considered in our fast moving disease area an old fashioned approach at getting to MRD negativity fast and hard, compared against the smoothly applied break and reverse gear of ibrutinib monotherapy vs attempting to mimic the old aggression with two different combinations with ibrutinib (ie adding rituximab or venetoclax).
The real question will be in say ten years or twenty years time will people who started their treatments with one of these very different strategies be just as likely as each other to still have their disease under control with whatever they are then on?
Does starting ibrutinib sooner lead to long term benefits in the same way it seems to be in the short term compared to FCR?
Or does starting with FCR buy some extra years of health that only really become obvious a long way down the line. Would five or more years delay in Ibrutinib be a good or bad thing?
By which I mean is it possible that delaying the start date of Ibrutinib delays the time it might stop working?
Or perhaps because all current treatments are good and there’s so much else coming down the pathway perhaps it does not matter at all what we start with.
There is much about all this that is confusing. But we must not lose sight of the fact that each of these medicines kick CLL cells into touch in a meaningful way for most people, but that nobody’s suggesting anything we have currently licensed will be a true cure for the majority of patients.
It’s very easy to become either attached to the drug you have taken or be full of buyers regret if you feel you’ve missed out on something better.
Truth is most of us especially the younger ones will probably need to be on more than one different treatments over our illness course. And even if the first medicine doesn’t do as well as we hoped we can always reach for a second or third even.
And for sure it sounds like a second opinion from a cll specialist is important for this case and indeed for all of us when a particularly difficult decision point looms.
Whilst this is all very interesting Adrian, if we address the poster’s specific enquiry, at this stage he’s clearly keen to find a way to greater treatment efficacy at this stage.
We can have academic debates about how important MRD is on the CLL landscape but for Litevibe, an ALC of 85 a year in with Ibrutinib is suggestive of another look at the treatment approach he’s receiving.
I’d urge him to seek another opinion and explore all available options out there on trial or non trial.
When I heard Prof Hillmen speak at Leeds about the amazing success of the I&V Clarity Trial, I had a strong impression he expected to see this rolled out widely. However it’s difficult for us to know the full financial availability and access to these drugs in other countries at the moment. It’s been very useful therefore to hear from our members from the US on this. There’s a tremendous emphasis on Flair on the site and we need to be mindful that it has limited application.
Newdawn
Actually, whilst I do definitely agree that he should ask for a second opinion, it is very possible to argue (and I wouldn’t be surprised if his specialists may say this) that perhaps the ibrutinib is working just fine.
His count is significantly less than 50% of what it was at the beginning. That’s part of the definition of a pretty good response according to the guidelines. Depending of course on what else is going on.
Perhaps the specialists view might be that Ibrutinib has caused a response and should be allowed longer to work. Depending of course on symptoms and node size and the whole overall picture.
I’ve seen too many promising ideas in medicine prove not quite as good as we thought they’d be in clinical trials. Sometimes in the UK outside of clinical trials medicine in all areas has been accused of being too slow to adapt to new ideas. It is also possible to be too fast,however. And personally until there is a Strong consensus among a group of specialists that it’s time to start using combinations like V plus I outside of a trial I don’t think we should rush to do that. Or not at least unless the individual realizes that what they are doing is experimental and they are effectively putting themselves into an uncontrolled experiment situation.
And please don’t think I am trying to put a cold blanket on the whole idea of this particular combination. Far from it. If I hadn’t thought it sounded like a very reasonable thing to be studying in a clinical trial, I wouldn’t have volunteered for FLAIR, since as we know that’s one of the options.
Flair will have huge applicability to the whole world when it’s data starts reading out. It’s one of the few large more real world but still randomised trials out there.
If the V plus I arm beats all the other arms in the mid and long term it would be a good grounding for arguing that it could become a new standard first line treatment even outside trials. And indirectly this would support the use second line or third line too
Anyway I think we all agree that it’s worth him getting a second opinion, and seeing what is said.
Things are changing all the time in this field. And individual cases need to be throughly assessed in their entirety by a good specialist before specific recommendations can be made by physicians.
I definitely think that the British haematologists were right when in their 2018 guidelines they argued that due to the nature of the disease and how much we still have to learn, that wherever possible CLL patients should currently be managed in a clinical trial environment.
This is because of the uncertainty that exists about what is the best treatment. Which means that allowing a random choice to be made gives an individual patient the best chance of getting whatever turns out to be the best treatment in the study. And of course at the same time it gives the gift of clearer knowledge to future generations.
There are many studies ongoing at the moment and I would encourage people to at least consider whether it is right for them as an individual to be part of one. It won’t be right for everyone of course. But I suspect Flair might not be the only trial I personally volunteer for over the years unless of course I beat all the predictions and somehow manage to ace a cure out of FCR!
Switching from ibrutinib to venetoclax while ibrutinib is still working would be just as problematical as adding venetoclax. Venetoclax is approved in the US as a second line drug after failing the first, adding V to I is still investigational.
Now you might convince an insurer that they would be paying about the same if you stopped ibrutinib and switched, but that would be very much dependent on an insurance company that wants to work with you and has the flexibility to do so.
That said, from all I have read, stopping ibrutinib while it is working and you are having a good partial response, would not be advisable.
Litevibe, I think there are a lot of doctors in the US, and probably elsewhere, who think adding venetoclax is a great idea for you. There are trials that you might be eligible to enter. And its possible you can do it off label with an understanding insurer. I am exploring the same option and I'll let you know how it works out for me.
I do agree that a partial response on ibrutinib especially if that response is gradually leading to more and more response (ie a dropping lymphocyte count etc) then it may well be sensible to continue that treatment. We can talk in generalities. But we really can never advise another member on here what the best course of action is for their specific case. That’s what the cll specialists are for.
Litevibe,
You are your best advocate. I can only speak for myself but getting a second and third opinion can’t hurt. There is so much going on and things changing so fast that it’s a lot to digest and treatment decisions are huge, timing of when and what to do. I would arm myself with this information and if the answers are consistent whatever those opinions are then you have your answer. If you have conflicting opinions then you have to make that call if you want to change or remain with your current treatment and provider, but exploring additional opinions I believe is important and comforting, especially with so much going on with new and emerging treatments. Hope that helps
WOW! I am truly Blessed to have a great group of people respond to my thread. The biggest issue is I am just an expense in the Insurance providers eyes, ecspecially when the medications are over 100k a year. I am just trying to excercise all options at this point, since my Insurance is Employer funded, one day the Board could say we are not paying for that medication anymore and I don’t have a backup. I Just feel like a pawn in the Insurance business.
That always weighs deeply in the back of my mind and can be somewhat depressing at times!
In your position, I would look into the cllsociety.org on line second opinion program. I know that they currently have slots, and recently received funding for this year. I believe that one of the specialists involved in the program could give you sound advice about how to best proceed, and, if there is a clinical trial that is a good fit, could point you in that direction.
The advantage of a clinical trial is that the trial drugs would be free. If there isn't a clinical trial for you, they might also be able to direct you to a CLL specialist near you, in a major research center. Often those centers have a staff dedicated to finding funding, or other options, for patients. Two people I know are currently getting Venetoclax for free through the company, thanks to their specialists. Often these specialists will work with a more local doctor who deals with routine monitoring.
Litevibe, This is definitely a paper that you need to read: "Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy"
Blood 2014 123:1810-1817;
bloodjournal.org/content/12...
Check out the authors....some of the top CLL specialists;
Jennifer A. Woyach, Kelly Smucker, Lisa L. Smith, Arletta Lozanski, Yiming Zhong, Amy S. Ruppert, David Lucas, Katie Williams, Weiqiang Zhao, Laura Rassenti, Emanuela Ghia, Thomas J. Kipps, Rose Mantel, Jeffrey Jones, Joseph Flynn, Kami Maddocks, Susan O’Brien, Richard R. Furman, Danelle F. James, Fong Clow, Gerard Lozanski, Amy J. Johnson and John C. Byrd
Progression Free Survival of patients with persistent lymphocytosis is not inferior to those achieving complete or Partial Remission by 12 months. This is a landmark analysis day 365 comparing patients with PR-L at 12 months vs those with CR/PR at 12 months. There is no statistical difference between these groups, although there is a trend toward improved survival in patients with PR-L.
Please read this last sentence again. I certainly hope that you do fall within this group!
gardening girl
Can you post a functioning link to the article? Thank you!
Here it is. bloodjournal.org/content/bl...
Interestingly the group described as with ongoing lymphocytosis were people with much less of a Response in terms of lymph count than seen in the original quarry of this Train. They are defined as people who hadn’t seen a 50% drop in their baseline levels.
So sorry, see if this works:
bloodjournal.org/content/12...
If this link doesn't work for you message me with your email address and I'll email a pdf.
You may find the link below of interest.
In addition, investigate the research data and doctors specifically involved with the study of I+V.
clinicaltrials.gov/ct2/show...
JM
Litevibe, need to know a bit more about your Dx to offer opinions. Specifically are you 11q? 17p? Unmutated? Complex karytype? These blood factors describe high risk CLL patients. And high risk patients need second opinion from a cll specialist. And typically can justify V and or after I.
I'm not a doctor but I think you probably don't have anything to worry about yet as the cells circulating in your blood should be senescent.
Without additional Rituximab the Ibrutinib can take quite a while to bring your lymph count down and your count was very high to start with.
If all your nodes are negligible (perhaps confirmed by CT) that's another positive sign of continuing response, if they start increasing that would probably be indicative treatment failure unless you have a concomitant infection.
It might be worth asking your Dr if they tested for CD49d on your lymphs when they did your profile. This is associated with a poorer response to Ibrutinib and a combination therapy is needed.
More about it here: eurekalert.org/pub_releases...
and more technical paper here: jem.rupress.org/content/215...
Wishing you all the best
Jackie
Taken off ibrutinib
Am I getting better or worse? 
FCR versus Ibrutinib
Stopping Ibrutinib?
