Asking on behalf of my husband. He’s been stage 4 cll for 2.5 years without any treatment yet, he’s 42 years old and in great shape/very active which has really helped him. He’s been very lucky but it seems like it is time now due to his blood results and spleen size. His doctor wants him to start imbrutnib but my husband does not want to take that because he has always been extremely sensitive to any pills or medications. He always gets side effects from anything he has ever taken.
Is anyone else similar with the same issues and if so how did you respond to the medication?
What other treatment options would he have?
Any tips or advice would be greatly appreciated!
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Chewy5
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i am currently on ibrutinib for over a year. i have had few side effects and what i got have disappeared as time has gone on.
However-if i was starting now- acalabrutinib (Calquence) is the btk inhibitor i would ask for
The new non-chemo CLL treatments are rarely effective enough on their own to eliminate CLL to the point where it is unable to be detected i.e. achieving uMRD. So if your husband opts for a monotherapy, such as Ibrutinib, or the recently approved Acalabrutinib which has less side effects, then he will need to be on the drug indefinitely, as in 4+ years before having around a 10% chance of achieving uMRD. The side effects with Ibrutinib and Acalabrutinib generally fade with time, but there is a risk of developing high blood pressure on these drugs (about 10 - 15% on Ibrutinib and about half that on Acalabrutinib). A considerable percentage of those on Ibrutinib can't tolerate it and either try and see how they can manage on a reduced dose (for which we still lack evidence of long term effectiveness), or switch to another drug, such as Acalabrutinib or Venetoclax.
Given your husband's extreme sensitivity to medication, he may want to consider a 6 month course of Obinutuzumab/Gazyva (which has FDA approval for use with Chlorambucil, but can be given without it as specialists consider the Chlorambucil doesn't add much to the treatment). That's not likely to give him a long remission.
Then we come to the limited time combination treatment options. Ventoclax+Obinutuzumab (V+O) has been approved by the FDA,with other combination treatments being trialled. Your husband should ask his specialist whether V+O might be a better choice or if he can join a combination treatment trial through his specialist's practice. Treatment with these lasts a year or more and several promising combinations are currently being evaluated in clinical trials. Your husband would be trading off the risk of longer term potential side effects, for perhaps a greater risk of challenging side effects, but for a limited time. We don't have any way of knowing whether and if so, to what degree, we will experience side effects with given drugs, unfortunately.
Given your husband is only 42, if he is mutated IGVH, then he should consider FCR chemoimmunotherapy, simply because it's just a 6 month treatment and he would have a 55% of chance of achieving a very long remission - approaching 20 years for those on early FCR trials. A good chance of a long - perhaps indefinite remission may be very attractive to him.
Finally, your husband will need to consider the relative risk of exposure to the coronavirus involved in any travel/hospital attendance/admission for treatment. More visits will be needed on a clinical trial and treatments involving infusions will involve hospital visits. If his treatment includes Venetoclax, he may need to be attend hospital for observation during the ramp up phase.
If you live in the USA, the CLL Society Expert Access program is available to your husband. This will give him a free of charge second opinion from a CLL specialist. cllsociety.org/cll-society-...
You don't say where you are based but if you are in the USA then this would be my plan.
First, get my genetic testing done again (FISH not mutation test) if it hasn't been done in the last 6 months because it can change so that you pick up new mutations. Probably important to know even if you're having a new, targeted therapy.
My treatment goal would be to get a treatment that could give me undetectable disease (known as U-MRD) because that is the best predictor of a long and sustainable remission.
If I was unmutated like your husband then the evidence shows that chemo-immunotherapy FCR or BR or Chlorambucil will almost certainly not provide long and sustainable remissions. The treatment is generally approx 6 months long but with a remission statistically, probably an average of just 3.5-5 years for unmutated patients so not great. In addition there is the approx 10% risk of significant bone marrow damage which will last forever and may lead to myeloid leukaemia in the years ahead.
The new targeted treatments fall into two groups - whether they are long term, continuous treatment or time limited treatment. The continuous treatments rarely get you to U-MRD and the side effects are sometimes significant enough to stop.
With Ibrutinib, a BTK inhibitor, 78% of patients either developed significant hypertension needing treatment or had their hypertension get worse (Dickerson et al Blood 2019) putting them at a two fold increased risk of cardiovascular disease and stroke. Second generation BTK inhibitors such as Acalabrutinib have a much lesser risk of these side effects but the data is not yet very mature so there may be other side effects not yet apparent.
The time limited targeted treatment is Venetoclax, usually given with a monoclonal antibody, either Rituximab or preferably Obintuzumab. This drug has the potential to get you to U-MRD with just 1 or 2 years treatment. Neutropenia and possibly tumour lysis syndrome at the start of treatment are probably the most significant side effects and steps are taken to ensure this doesn't happen.
Possibly the best treatment is a combination of a BTK inhibitor (such as Ibrutinib or Acalabrutinib), Venetoclax and a monoclonal antibody but it may be difficult to get that outside a trial. Trial results with that combination have been spectacular with patients quickly getting to U-MRD status but again the data is relatively immature as this combination has only been around for a couple of years. Again this is a time limited treatment.
I haven't mentioned Idelasilib because the safety profile of this drug is generally unacceptable to clinicians and patients.
I would be looking for a clinical trial with a combination of targeted treatments.
Your husband is very young and has a lot of living to do. He needs the best remission possible, not to need to go from one treatment to another over a short number of years.
I am rather new to this site. You always seem to have fantastic advice. What is FCR? Today my doctor suggested Gazyva (alone). Do you loose your hair? Do you know anything about this drug? I know nothing about it.....I am getting so confused. I just need to make a decision!!! Very frustrated today!!!! Sorry
Older 'chemo' treatments work through alkylation - using drugs that cause breaks in the DNA when a CLL cell divides. Fludarabine and Cyclphosphamide (the FC in FCR) and Bendamustine (the B in BR) work this way. The R in FCR and BR is Rituximab, a first generation targeted therapy, which is a monoclonal antibody that locks onto CD20 protein cell markers found on B-lymphocytes, including CLL cells. FCR was developed at M D Anderson about 20 years ago by a team led by Dr Michael Keating. It proved to be the first CLL treatment that significantly extended life expectancy. The problem is that CLL cells without the 17p (short chromosome) arm or a working TP53 gene on 17p, lack the ability to detect CLL cells with DNA breaks and undergo apoptosis. So treatment of CLL patients with these markers is ineffective. FCR and BR also don't generally work well with unmutated IGHV CLL.
Obinutuzumab/Gazyva is a second generation (humanised) version of Rituximab, which contained hampster DNA. It has proven better than Rituximab. I've been treated with it in a combination Acalabrutinib + Venetoclax trial. Other than having a scary 'shake' infusion reaction the first time, I really didn't have any side effects, though it was hard to tell, given I was on other drugs.
Gazyva is FDA approved for CLL treatment with Chlorambucil, a very old alkylating agent that most specialists consider adds little to the treatment effectiveness and may even omit it. It's just that it was used in the clinical trial leading to its approval.
You are unlikely to get a long remission out of a Gazyva treatment unless it is combined with another drug or drugs.
None of the CLL treatments result in complete loss of hair, but perhaps partial hair loss, or with Ibrutinib, wavy hair! My wife though my hair thinned, but I didn't notice the difference.
We do not get free rides with any Cll treatment. If your husband has mutated IGHV Cll, he might consider fcr which is a limited term chemoimmunnotherapy. Fcr is typically six cycles of infusion therapy once a month for six months. It’s possibly curative for those with mutated IGHV Cll. It is considered more toxic than ibrutinib and can increase the risk of secondary cancers.
Outside of a clinical trial the other options are probably ibrutinib or venetoclax plus obinituzimab. Ibrutinib is a pill a day indefinitely with mild to moderate side effects for most people. Venetoclax is an oral pill treatment too, but it can produce a remission, no one knows how long.
I think of Cll has a lifetime fight, so with all the new drugs in development I personally would take a do the least harm now strategy and start with ibrutinib. Other drugs can be added later as they prove themselves in clinical trials. I think all three are reasonable choices. I would not choose fcr if I had unmutated IGHV Cll, but some unmutated people do well on fcr if they do not have 17p Cll.
That’d exactly my markers. I seem to have bucked the trend and done really well on FCR (in October I’ll have got to two years after starting and despite quite aggressive disease theses no sign of relapse yet and I got to MRD undetectable.
Of all the options available to you in the USA I would definitely include the covid risk into the calculation.
That might weigh against both FCR venetoclax and obinituzimab leaving really acalabrutinib or ibrutinib (and if possible acalabrutinib seems to be stronger but more easily tolerated).
But if you are not that worried about covid then venetoclax plus obinituzimab might be a good option to consider or one of the combination venetoclax trials as there is a good chance of getting to MRDU which most people are assuming will lead to at least in some cases really long remissions like FCR that might even be a cure.
I would definitely make use of the CLL society second opinion service and / or find out where your nearest centre running clinical trials for CLL is. At such a young age you want an experts view. You don’t mention what blood results are leading to treatment at the moment and it’s just possible that a cLL expert might feel it was better to wait a while before treatment especially during the pandemic. Of course it depends on what exactly is leading towards this decision
I am 13q mutated. I only needed 3 rounds of FCR. I responded quickly and it was uneventful.
I didn't want to take daily pills. May be necessary in the future but FCR has put me in remission almost 2 years. Discuss with his specialist all the options. If he starts daily pills and then change his mind, chemo usually does not work. You can always stop chemo and start pills. Second opinion is important too. 💕
In theory, chemo is likely to work after non-chemo treatments, but with the move away from chemo treatments and the increasing availability of new and varied non-chemo treatments (i.e. targeted/inhibition/small molecule treatments), there is generally no need to resort to a chemo based treatment (i.e. a treatment that works by scrambling the CLL DNA so that the CLL cell hopefully self destructs through apoptosis).
Actually, provided we don't develop resistance to a non-chemo treatment, it's considered probable that we may do as well on a repeat of the same non-chemo treatment. That wasn't the case with chemo treatments, particularly if only a short remission was achieved. That's because of the development of sub-clones with 17p del and TP53 mutations.
My experts said that I could take Ibrutinib or have chemo. To help my decision, they said if I started Ibrutinib and then decided to try the FCR, it ( chemo) probably would not work. So they wanted me to be sure about my decision.
I never asked for specifics as to why. Maybe it has to do with markers or being my first treatment? 💕
It would be interesting to know why. It was recognised that at least with chemo treatments, you get your longest remission with your first treatment. While that's probably the case with newer, non-chemo treatments, the different efficacy may mean that's less important.
I've seen you post many times that your dr told you FCR isn't effective post novel agent and there is zero data to support that statement that I've found. I too would be interested in your dr sharing whatever it is that made him tell you that. Like Neil said it's probably just not a logical sequence of treatment but clearing that up may prevent you from passing along unproven information.
I don't feel I need to clarify anything. Any information or opinions we express are clearly information that was told to us by our doctors and each individual should do their own research. At the time of my experts appts, I didn't really care why they said what they did. I trusted their research, experience and reputations . I probably would not have understood their reason. I don't get into the technical stuff with my doctors.
But if two extremely well known CLL experts both me the exact same thing- I would not say I am passing on any unproven information. Everyone knows they need to do their own homework and ask their doctors.
My husband is unmutated, 58 y/o, very healthy and is on the Ultra-V trial at Mayo Clinic in Jax, FL and he's had no side effects. I would recommend that you find a CLL specialist before starting any medication.
I would second the notion of possibly exploring trials, depending on logistics.
We were in the same boat as you a month ago - My husband is 57 and very fit and active. Diagnosed 18 mos ago... 13q, unmutated. We were leery of a treatment that didn't have an end.
After looking over some options he went with a 3 drug trial and has just started the Ultra V trial last Tues (in Nashville). Though it is early days yet, so far he is tolerating everything well and his blood work has made remarkable progress in a week.
Here is the thread where I asked the very question you are asking if you want to see some more thoughts about the crazy decision time:
Do you happen to know if he is NOTCH1 mutated? We did see one study that pointed to trends of shorter progression free survival for the NOTCH1 mutated group when on ibrutinib as monotherapy FWIW.
Thank you all so much. This is all very helpful and I will definitely be researching some things. He has a great specialist Dr. Rai, but he’s definitely up there in age so I’m not sure if he’s making the right decisions for my husbands concerns.
I am also sensitive to drugs. Have trouble with antibiotics as well as Tylenol. I have been on ibutrinib for 3 1/2 years with no problems. In 2 months my blood counts were normal. Only side effects are curly hair and weak fingernails. Ibutrinib saved my life. I am so thankful. I pray you will have good results. BTW, my brother with cll almost died from a blood infection during chemo. Switched to ibutrinib with no problem. He is back to work and well.
I realize how difficult the choice can be at this stage so just let me share my experience.
At 66, I was diagnosed Stage 4 CLL in January of 2018. Was on W&W until January of this year when my oncologist said my size of my lymph nodes and spleen size and the condition of blood work had reached a point to where I needed to consider treatment.
Instead of spending years on ibrutinib, his recommendation, if I could tolerate the ramp up, was obinutuzumab and venetoclax. A one-year regimen and I’d be done.
That’s the course I chose starting in February and, although the first cycle of obinutuzumab was slightly uncomfortable for about an hour, outside of that, and I’m including the 2 day venetoclax ramp up hospital stay, I’m now nearly halfway with practically no side effects, lymph node and spleen swelling and size has gone way down and my blood work has improved substantially.
So, I thank my oncologist, and God, for setting me on this course. All I can say is that it’s worked for me so far.
my view: as he is ummutated and for other reasons no FCR. Chemo can cause other problems like mutate DNA and cause other cancers possibly. If he is sensitive he'll be sensitive to FCR as well right? Ibrutinib amazing for many. With time treatments will get better. Ibrutinib will buy him time. For me minor side effects for a few months..easy bruising minor joint pain GI issues, no hair loss (actually helped my hair) all have resolved. Take it like a vitamin. No big deal. Maybe Acalabrutinib better. Also consider a course of Gazyva first. Stay positive..there are many treatments and they are getting better! I chose to hold off on Venetoclax so I had another weapon in my back pocket but no need for it now. Doing well for years on Ibrutinib. For 1st treatment great majority doing well even after 5 years. More effective as a 1st treatment. I see no downside of Ibrutinib and little possible damage unlike FCR chemo... since he is unmutated.
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