Hello, I am new here. My husband needs to start first time treatment for CLL as soon as possible. He was given info. about the clinical trial which adds Venetoclax to Ibrutinib and Obinutuzmab. Half of the participants will receive the Venetoclax. His other option is to be given just the Ibrutinib. We do not know how to make this decision. Since he usually gets side effects to every drug he takes, he is leaning strongly towards just taking the one drug. His oncologist has not really discussed the pros and cons but we will meet with him again in a few days. Any advice or input would be appreciated. Thanks!
Ibrutinib and Obinutuzumab with Venetoclax - CLL Support
Ibrutinib and Obinutuzumab with Venetoclax
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Johnnyislander
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Hello - the various therapies available for CLL are a bit of a maze to be negotiated for the newcomer. All drugs will have side effects, but different people will respond differently. Some experience them mildly and others severely.
The use of either Ibrutinib or Venetoclax as a mono therapy involves taking the drug for an indefinite period. Venetoclax, Ibrutinib and Obinutuzimab as a combination therapy is intended to be used as a time limited therapy of 24 months or maybe less depending upon the response. The idea is for a long remission from therapy once the CLL cells are no longer detectable in the bone marrow.
Your husband's choice is between a time limited therapy or an indefinite therapy. It would be advantageous to discuss this with your specialist.
Others on this forum will probably be able to refer you to videos and papers discussing these therapies in detail.
Good luck.
Thanks for your reply. I’m also thinking he should see a CLL specialist that he had a consultation with a year ago. He sees a local oncologist right now. Thanks again. The idea of remission is certainly the preferred outcome!
Yes, definitely do consult an actual CLL specialist before making this decision. seelel summed it up well - the triple combo could lead to long remission that is drug-free for your husband. whereas the ibrutinib alone is an "always" drug. You never stop (until you become resistant to it and need to switch to something else). However 3 drugs could cause more side effects (toxicities) than 1 drug.
I have been on ibrutinib 17 months and have no side effects - and it seems to be completely controlling my CLL. Wouldn't know I'm taking any drug, and wouldn't know I have CLL. I am not sure which choice I would make if I were in your husband's position.
Good luck!
kim
Thanks for your input. It is encouraging to hear!
Johnnyislander: I’d definitely make it a point to sit down with my CLL specialist before making such an important decision. The future of CLL treatment lies with combination therapies. So I’d opt for that option assuming my specialist didn’t have specific reasons to steer me away from that choice.
I have a friend who is a kidney doctor at a large Boston hospital. He is eighty years old but looks and acts about 65. He still see patients, teaches at a medical school, conducts research and travels the country speaking at medical conferences about his areas of expertise. I met with him last Labor Day to talk about my SLL. He quickly told me he couldn’t offer any meaningful medical advice given the complexities of my disease and the changing treatment landscape. However, he did share two pieces of “big picture” advice which have stuck with me: 1) Be a tireless advocate for yourself as it is easy to get lost in the medical beurocracy and 2) Make certain to utilize clinical trials where possible as often the best treatments are available through these programs. And equally as important, participate in trials not only to help ones-self today but to help patients in the future as a repayment for those who came before us and made current medical treatment possible.
I really appreciate your reply. The “big picture “ advice makes a lot of sense.
Yes, definitely see specialist. MD Anderson in Houston has clinical trial with venetoclax that seems to be having great results
See a CLL specialist for sure before treatment - I just did and approach, full explanation and many options presented. I don’t know your husband’s age or markers etc, but one thought is ‘don’t use all of the CLL bullets’ at once if not indicated. If his markers support short term treatment with one drug for remission, save the other drugs for later, if needed. Just a thought.
Thanks. That’s a good point and appreciate the input!
I start testing tomorrow for this study. My dr. Seems to think this is a good combination.
Others have explained this well. But if you want to try and obliterate the disease and have a period of time (hopefully many many years long) where you don’t have to take treatment and the illness is essentially not there then the combination treatment is the way to go. Monotherapy Ibrutinib should control the illness well but will be very unlikely to get to the point where it’s no longer detectable in the body.
FCR is a combination chemotherapy which was shown to be much better than using any of the three components alone. They are now looking at combining the newer drugs in order to try and reproduce that better ability to kill the cll cells than using just one drug.
Links to research showing that FCR is a better choice than “using any of the three components alone”? I think that there are a lot of factors that a doctor would consider before suggesting FCR or any of these drugs, alone or in combination. One would certainly be FISH results. This patient is fortunate that he has choices. Not everyone does because of geography or economic status. Hopefully I will be around long enough to see that change.
I think he meant FCR is better than F, C or R alone.
Exactly. Originally F or C were given alone. Then FC was given. Then there was a study that showed FCR was better than FC. The hope therefore is that if we give V+I+R or a descendant of one of these drugs (obinutuzumab is son of rituximab and acalbruinib is son of ibrutinib) then the results will be better than any drug given alone.
And in the case for example of Ibrutinib on its own it is great at slowing down the growth of CLL, or even reversing it, but not coming anywhere close to abolishing it.
We are entering rapidly into a time of choice and uncertainty in terms of which medication is best for us, and which order we should go in.
Do we go for attempting to abolish (FCR and the modern combination approaches such as proposed in the study this patient has been offered)
Or do we try to contain it knowing that the CLL will be still there but we are able to Co exist with it as it can’t grow (ibtutinib monotherapy)
Do we want to throw a combination of almost everything we have at it first time round in the hope of a cure, or at least a very long remission, and that by using combination treatment we will be less likely to cause resistance to that drug (the idea of FCR and also the newer combination treatments).
Or do we want to use only one drug at a time in the hope that we can string together a sequence of remissions? UK policy outside of a trial at the moment is this for non 17p/TP53 where FCR is used essentially to delay the start of Ibrutinib or venetoclax. Some data suggests that may not be the best approach in the short to mid term (ie most studies suggest Ibrutinib is more effective than FCR at preventing relapse even though it doesn’t usually cause MRD negative status). But we don’t know yet in the longer term whether that difference continues especially if FCR patients can take ibrutinib second line.
Just for clarity: MRD-ve status is close to abolishing the disease tho it’s possible some cells are still “hiding” as if for example we are looking at 10,000 cells and none of them are CLL there may still be some CLL cells if you could look at 100,000 cells. MRD-ve status doe not therefore mean a cure but it could be some of the patients who are MRD negative may actually be cured or at least be due to relapse in so many years they may as well be cured. If someone said I had a handful of CLL cells left and I’d probably relapse after 40 years at 48 that would be basically as good as a cure for me.
I’ve had, FR, BR and now Ibrutinib. I can easily say that I can take three pills daily for the rest of my life as long as it continues working. I have no negative side effects with Ibrutinib. My numbers are great and I have lots of energy. Ibrutinib wasn’t an option when I had the two previous treatments or I would have jumped on it. I can once again do all the things I enjoy. You would never guess I have CLL/SLL. Life is great with three pills per day. Sally
That’s great for you. And many find a similar efficacy. As a matter of interest what are your numbers? Did you reach MRD negative status? Of course if you feel well and the CLL is either stalled or in reverse then it’s probably not that important a question. You are an example of why ibrutinib is considered such a great drug.
My numbers are all in normal range and have been at around 3-4 months on Ibrutinib. I’m unmutated, Trisomy 12, stage IV. I have labs done every 2 months and visit my specialist every 4 months. My white count never shot up like the majority of people on Ibrutinib. I had gigantic lymph nodes that dissipated within days. My spleen disappeared. I can no longer feel it. I feel alive again. Do I want anymore tests to see if I’m MRD negative? No, because I don’t care. Mentally and physically I’m strong so I’m happy. Hope you continue to do well with your treatments. Best of luck, Sally
Sally, that’s great. Really pleased for you. As you rightly point out at the moment it’s far from clear whether pursuing MRD negativity is really necessary. Some experts believe it’s really important, others think not. And if you feel well and your numbers are good at least for now I’m sure that you are totally fine to continue. I don’t think it will be many years though before people start to take folks like you who are stable and try adding a second drug for a while with a view to getting to a point that all drugs can safely be stopped. But right now the evidence isn’t yet rock solid on that. So enjoy the amazing drug that is Ibrutinib. Hopefully you will stay really well for years. We are really ALL so fortunate that there are several good options for treatment these days for us.
I would happily add a second drug if my specialist recommended it. I agree we are so very fortunate to have so many options. Appreciate each and every day. Sally
It’s not quite at that point yet where such an idea is mainstream outside of a clinical trial. But maybe in the future . . . Great advice to enjoy every day!
That is great to hear!
Thanks, so much to think about!
Hello Johnny,
I am also slated to start the trial. (19 month trial)
Arm A is Imbrutinib and Obinutuzimab
Arm B adds Venetoclax after 3 months
It was explained to me that during the trial if the 3 drug approach does not work or symptoms or numbers show an issues the Venetaclax will be stopped. The opposite is also true. if I am in Arm A and the Arm B side of the trial shows great results I can possibly add the Venetaclax to my therapy. I can also end the trial at any time I feel is needed,
My wife and I along with my sister in law who is a doctor have discussed the trial and the possible side effects. I am 55 and I do not have any symptoms other than my numbers have reached the point where treatment is needed. My Hemo/Oncologist can do the 2 drug therapy if I opted out of the trial.
I look at it this way. I am hoping to get into Arm B.
All the costs are taken care of by the trial. Drugs, Ct scans, Bone Marrow biopsy monitoring etc. Also all costs of future drugs if we get a positive result.
If I choose to opt out then any future therapy is up to my insurance company and myself and we know insurance companies are there for the profit not the cure.
I went through the mental drama in my head after reading all the side effects and have to roll the dice. I will take my shot to get to remission and be able to work and retire and enjoy a full long life without CLL defining my life.
Hope this helps your husband and yourself.
Joe
This helps a lot. Everyone has been very helpful. I called the office of the CLL specialist that my husband saw about a year ago. She will be gone until May. They did say they will have other oncologists look at Johnś records and get back to us. My husband is 69 and his white blood count is now over 300,000 but he still has basically no symptoms! His blood work is showing concerns such as anemia, so he does need to start treatment. I think he has an unmutated something. Sorry that neither of us like to remember the specifics. So glad there are options out there and we are hearing about good results.
I had the threefold trial trisom12 unmutated Stage 4 cd5 cd19 cd20 23 38 52 79 500000 lymphocytes hemoglobin6.1 8 months Im MRD negative bone marrow free since January2018 No more medication just checkups
MsLockYourPostsPassed Volunteer
No one here can tell you which way to go with treatment, but I would certainly have your husband discuss his options, in light of his particular presentation of markers and symptoms, with a specialist familiar with his case.
We are all very different. I personally would normally have trouble dealing with a phase three trial and being randomized (guess that I’m too much of a control freak), but this one has crossover options. That would make me give it serious consideration if I were in your husband’s shoes. But, I would want to hear all of the pros and cons of my various options from my specialist before making a final decision.
There is a lengthy thread ( very lengthy - you would want to skim through most of it) on cllforum.com where several participants in the triple drug combination wrote about their experiences. There are also members there who have done trials with the two drugs. If you use the same title there, they may find you before you find them. Both this site and that one have many posts about Ibrutinib.
Remember, when reading personal accounts, that those experiencing problems are the ones most likely to post, so don’t get too wrapped up in any negative information you come across. There are people using all three approaches who are doing incredibly well.
Keep us posted. I don’t think that there is a wrong answer in your husband’s case, but there might be a preferred answer, given his particular CLL, as well as how he personally feels about each choice.
Interesting that you would struggle with being randomised. I was very happy to be randomised in the FLAIR trial because it seemed clear to me that there wasn’t a clear answer about what was best. And when we don’t know then randomisation makes sense. Maybe the hard step is recognizing that we don’t know and actually nor do the experts (or they wouldn’t be running the trials)
All the drugs in this study are already licensed.
The new “son of rituximab” (the O drug in this trial) has a great history behind it. And to combine it with ibrutinib (I) makes a lot of sense in theory. The idea is that the I will stop the cll cells from dividing and drive them out of the lymph nodes, therefore hopefully making it easier for the O to bind to them and cause the cells to die. Joint working!
The V drug also kills CLL cells very effectively by a different method. So the hope is that the three together will be even more powerful.
So there’s a lot of excitement about this particular combination of three drugs potentially becoming the gold standard of treatment.
Logically we would expect such a combination to work really well against CLL and be very likely to put someone into MRD negative status and hence hopefully a LONG CLL free remission would result. Also by using all three drugs together like this the theory would suggest you may be less likely to get resistance to any of them developing (a cell would need to be resistant to all three drugs to avoid being killed!)
If this particular trial had been offered to me personally a few months ago I would have been very happy to enrol in it if my CLL expert had advised me to.
Of course that’s not to say it’s the right thing for everyone to be in a trial. Some people will always prefer not to be. And that’s a personal decision.
"When we don't know then randomization makes sense." I would like to see that statement include, "for me". It doesn't make sense for everyone. Trials are having a lot of trouble recruiting participants, especially as the number of trials available grows larger. It's time for those designing them to pay attention to patient input if they want to recruit enough participants.
Part of my hesitation with regards to trials has to do with one trial in particular, in the past, in which the trial co-ordinators put pushing the drug ahead of patient safety. A friend was the poster boy for that trial, until the decision was made to increase his dose beyond a reasonable ramp up process. He is no longer with us as a result. Those running the trial were chastised very publically at ASH for their totally irresponsible action. It shut down the trial until things could be reassessed, and could have meant that approval was lost for one of the most important drugs currently in the arsenal.
Part of my feelings about phase three trials comes from having seen some that were very badly designed. The Chlorambucil vs Gazyva plus Chlorambucil trial is one which was clearly designed to push Gazyva through the approval process, not to compare the standard of care with something new. The result of this trial design is that many, especially in countries where there are no options for making adjustments to the FDA approval guidelines, end up taking Chlorambucil when it is not necessarily appropriate.
Many doctors in the US omit it from treatment, and I have heard of a few doctors in other countries telling patients, privately, to lose the Chlorambucil - not a good idea to do it on your own, as your doctor will be looking at results with the understanding that you are taking both drugs, but if your doctor knows..... In my case having to take Chlorambucil with Gazyva would have ruled the Gazyva out for me, because of the nature of my particular CLL.
FLAIR makes sense for many in England, where it means that one would get FCR, or might get it, but would also have a chance to get one of three other options not available otherwise, all of which have shown success. That doesn't mean that all trials make sense for all patients, in every country.
I'm glad that you find me interesting. I am not struggling with entering a phase three trial. There are a couple of well designed trials that I would look at twice. My decision would not be based on any mental struggle, but upon a careful consideration of the trial design itself, with input from my doctors, and the pros and cons of that trial for me. I would, in most cases choose to not be randomized, and would not consider a blind or double blind trial except in extreme circumstances. That's my opinion, which I have a right to, just as you have a right to yours.
Hi. First up I do agree that a trial is not for everyone and I mentioned that at the end of the post. So do agree with you there. I however think if more people understood just how little we know for sure about treating this illnesses especially now we have several treatments available and we have to consider sequence and whether monotherapy or combinations will turn out to be better. When we are talking about opportunities to help establish which combinations of newer drugs are the best well I think that’s for sure a worthwhile trial for the scientific advance. On here sometimes people make strong statements for or against a specific drug that are more based on emotion than fact. We need to be very aware of how crucial it is that people do design good studies and that we patients enrol into them. The British guidelines for treating CLL clearly state that due to the poor current state of knowledge “wherever possible” CLL should be treated in a clinical trial setting both for the good of future patients, but also because current patients are more likely to get better access to newer more specific drugs than in general practice, and in general receive slightly better care and closer monitoring.
Having been involved in creating and running trials before in different disease areas it’s very challenging to take account of all the different stakeholders desires.
And since the regulator ultimately decides which drug gets onto the market you do have to design a commercial study in order to the criteria in place at that time.
A lot has changed since the design of the studies you mention. And it’s easy to forget that.
Even FCR was a study designed to get R used alongside FC and you could argue that they should have considered having an R on its own.
But back then I don’t think anyone very thought a CD20 antibody on its own would be enough to treat CLL (especially as a cell doesn’t even need to adapt by mutation to simply shed the relevant antigen). In fact I don’t get the impression the uk experts I’ve spoken to would support monotherapy with any antibody.
As for your friend I am very sorry for your tragic loss. And whilst clearly mistakes were made, the sad truth is similar things have and will happen with new experimental treatments especially early in when we don’t know how to use them. People have died in CAR-T cell trials too.
We are very blessed and much in debt to the many who have volunteered for clinical trials in the past. To me volunteering in a carefully selected trial that makes sense and each arm has a reasonable chance of success is one way of paying that forward to those coming after us. But I would never want to put pressure onto people to volunteer for a trial as you do need to be clear about what you are getting into, and ideally have a genuine sense that either arm could be just as good as the other for you. We call that clinical equipoise which is vital for any trial to be ethical.
Rituxan was studied on its own and combined with fludarabine. There were also studies using FC before the FCR studies.
"To me volunteering in a carefully selected trial that makes sense and each arm has a reasonable chance of success is one way of paying it forward to those that come after us."
There are a couple of well designed (phase three) trials that I would look at twice. My decision would not be based on any mental struggle, but upon a careful consideration of the trial design itself, with input from my doctors, and the pros and cons of that trial for me.
Isn't that the way you considered the FLAIR Trial? You shared your consideration of the different arms of the trial vs your other options, and your consults with three specialists, with us in great detail, before committing to the trial. Aren't we saying the same thing?
Yes. I think we are. You thought I was saying everyone must volunteer for any study. Whereas I thought you were saying you were concerned about enrolling in any study. Truth is we have to be advised by our doctors about which trials are suitable for us. And hopefully over time studies are becoming better designed as we learn the lessons and the field evolves. Sometimes the FDA/MHRA/EMA can slow down innovation in this regard eg in many disease areas they still require placebo controlled trials which often therefore ethically enquire the kind of study you mention where a new drug is added to an older one to see if it is more effective and it means that the placebo patients at least get the older treatment.
Whilst there may have been smaller studies of rituximab in monotherapy the large trials that are quoted in the SPC (found at medicines.org.uk) were of the form FC vs FCR. There’s very limited data I can find of R being used in monotherapy which is interesting as at least some of our American members are treated that way.
In summary. I think we both agree: A good clinical trial mast answer a good clinical question we don’t already know the answer for. And it is a good idea for patients to carefully consider with their specialist doctor whether a particular trial is suitable for them as an individual.
I think we also agree that one of the psychological challenges of entering any trial is accepting that neither you nor your doctors actually know what’s the best treatment for you. I remember going deeper and deeper into the rabbit hole trying to figure out what was “best” for me especially as I was young (so even 5 year studies suddenly seem very short!) and eventually having to accept that we don’t actually know and hence a trial like FLAIR seams reasonable to me.
These decisions are incredibly personal and complex and I am sure we both agree that a consultation with a real expert in CLL should ideally occur before any treatment is initiated.
Hi,
I can’t imagine making a decision about what treatment is best to have without consulting with at least one or two CLL specialists.
All the best!
Hello Johnnyislander
I am in B+R treatment and it was tough decision to do that or Ibrutinib. I am over 65, so FCR was out. As I am un-mutated so normally Ibrutinib would be course of treatment. I was too late to get into trial at MD Anderson, but would have involved staying in Houston for months. I talked to 5 doctors for advice on which treatment. 3 CLL Specialists, 2 H/O. All had a different opinion, but all agreed that B+R was not bad choice either. Good luck. I know it is tough decision, but you have a lot of options if any one or more treatments do not work for you.
Ibrutinib and veneroclax have had some amazing trials together. Basically MRD negative , some new studies are involved with reducing. Your dose in medication once you become MRD negative
Can’t stress enough the importance of working with a world-class CLL specialist. This saved my life.
The history of cancer drug treatment has led docs to the use of combination treatments to minimize resistance.
I am in the Acalabrutinib, Obinutuzimab, Venetoclax trial at Dana-Farber. Everyone in it seems to tolerate the drugs well, as far as I know. This was certainly my best option. Other factors will help you and your doc determine the best course for him. Do you know how to go about finding a CLL specialist? I drive four hours to mine. Best investment of time I’ve ever made.
The CLL Society website cllsociety.org has a locator for CLL specialists.
Glenn
How is your job at Dana-Farber going Glenn?
Amazingly well. They are just as kind, compassionate, and committed to excellence “behind the scenes” as they are “on stage.” No wonder Forbes ranked them 8th best mid-sized employer in the country. Truly a special place and I’m privileged to think I can make a small impact on the quality of work done there.
I'm on ibrutinib and had a six month course of obinutuzumab. I think I've had nearly every side effect including AFib but I've found them to be manageable, better than my symptoms prior to treatment, and preferable to the alternative.
How many cycles
I just started in a European Trial with Obinutuzumab, Ibutrinib and Venetoclax. The trial is conducted with almost a 1000 patients, coordinated by the University of Cologne, Germany (Köln, Deutschland). There are a number of possible side-effects reported, especially if in the initial phases of the treatment. These side-effect can be well managed. But it is very important to rigorously follow the protocols. You can find these study protocols at the study-site. The study is called CLL113. My advice is to read the protocols thoroughly and use them to discuss them with your hématologist. It will make you aware of the incredible potential of the combined medication, but also of the risks involved. And use your inner intuition to take any final decisions.
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