Why are clinical trials our only option for the most part, why does our treatments cause more mutations and a cancer that is harder to treat, at some point, our cancer will outpace our options, and we will have none. We must be very intelligent on our line of treatments and make sure each we choose wisely, each needs to last more than a couple years, preferably 4 or 5 years before the next and pray they have something else to beat the mutations created each time.
ALCALABRUTINIB FAILING: Why are clinical trials... - CLL Support
ALCALABRUTINIB FAILING
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CAM729
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Unlike some of the earlier true chemotherapy agents, the newer targeted treatments don't damage our DNA causing more mutations. When exposed to treatment, cancers can often act more like bacteria and viruses. New cancer cells develop mutations to evade the treatments, much like you've undoubtably been reading how the Covid-19 virus has mutated. It's more of an "evolutionary pressure to survive induces the mutations" as opposed to "direct DNA damage from the drug causes mutations."
This fact is the reason the current thinking is to *not* necessarily be on the oral targeted agents forever. Original thinking when these came out was more along the "treating the CLL like diabetes" where one would just stay on the pills forever to manage the disease. But unlike diabetes, the CLL cells developed resistance. So now the thinking is shifting to "how long to we treat to get in a decent remission, where the CLL is kept at bay at least 2+ years, such that when it grows back re-treatment with the same drug is an option."
I think with all the research going on, and discovering more pathways critical to the cancer, there will continue to be options in the pipeline. Not to mention a planned drug holiday, so that the CLL doesn't get resistant and one can simply re-start the med. I am hoping to do this; I am getting re-tested for uMRD in December since January will be the 2 year mark for oral Venclexta. I am technically uMRD, but at 12 cells per million the last uMRD test after 1 year of treatment, we decided to continue another year, and see if that number can be drilled down further. If it's the same or less, I am pausing the Venclexta. I happen to have few side effects, so going back on it would be preferable to an unknown drug with unknown side effects for me.
Your rationale here seems valid and well-stated. My onc/haematologist shows no interest in fine-tuning her approach to treatment. I am wondering if it is the flow cytometry test you are referring to when mentioning the test for MRD. Is there a cost associated with it? I am in Ontario, Canada and am told this test is not available. Am thinking of travelling across the border to get it.
I was wondering wheat the test for uMDR was too. I don’t think any test has been mentioned to me either (UK based) and the success, or otherwise, of my treatment is based on blood test results. I would like to investigate having an ‘Acalabrutinib holiday’ but wouldn’t know how to begin.
Ask your specialist about taking a drug holiday. This concept is being discussed more and more lately in oncology circles. There isn't a lot of data suggesting who actually would benefit "the most". But other diseases where I have seen "drug holidays" tried, it seemed to be on a case by case basis.
physiciansweekly.com/study-...
cllsociety.org/2022/01/what...
From your profile I see you have an 11q deletion, which is associated with bulky nodes. If you go off the med, be prepared for them to grow again if you relapse. If you get 2 years before the CLL starts up again, IMO that would be a win. I am hoping for 2 years off, with my aggressive 17p del variant.
lankisterguyVolunteer
Hi CAM729,
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We both have been dealing with CLL for 12 or more years.
I've chosen the next new treatment 5 times, and had 6-7 rounds of treatments. Each time I had very few choices, but fortunately there was usually one or two, sometimes only a clinical trial.
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In the near future you may be able to try Pirtobrutinib nature.com/articles/s41408-...
if it gets FDA approval in the next few months.
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On a longer time schedule there are trials for bi-specific antibodies that target several different CLL specific surface proteins like ROR-1 or CD-1
See vjhemonc.com/video/z9erpexg... (there are 4 interesting videos at the bottom of that page- if you can decipher the "med-speak" used.
or onclive.com/view/fda-grants...
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Len
I feel the same way. It isn’t just the drug but if the disease burden is merely controlled the remaining CLL cells can make different clones with different markers
I have been on Acalabrutinib for just over one year. I asked at the beginning how long I would take it for. My consultant just said, for as long as you tolerate it and for as long as it is working. I know it's early days for me but my blood numbers are, according to my consultant, in normal ranges. I feel perhaps if I was to stop, then the numbers would climb again. So at the moment, my Acalabrutinib is my best friend!
Just for your information -- I had normal numbers with ibrutinib but due to minor surgery went off it and stayed off for three months and was still in remission. Then I went on the related drug acalabrutinib about a year and a half ago. My oncologist/ hematologist said what yours did but she often simplifies her approach and almost dismisses my questions. I do not trust her to have my best interest at heart and now wish to get tested for MRD. I might not be getting better numbers as i am taking half the dose. If i can get tested then i can decide if i should take the full dose or holiday from the drug. I have noticed that there are various approaches among doctors and thus we must also do some of the decision-making.
Why are you taking half a dose?
When you say you are taking half a dose of Acalabrutinib, do you mean you are skipping one of two capsules per day?
If this is the case, your numbers would likely not improve since this med only works for 12 hours. So, effectively you take a drug holiday every day for a half day. This does not make sense.
I took 2 out of 3 pills when using ibrutinib and stayed in remission, took holiday of some months and went onto acalabrutinib. My numbers have been steady all along for 5 years. I would like to take 2/3 dose but 2 pills cannot be divided that way. All my life I have used smaller doses of most meds without problems. They recommend the dosages used in trials which would be maximized i surmise to increase probability of success. I am trying to minimize side effects. Mainly arrhymia.
I understand that Calquence is now available in pill form as well as the usual capsule. The pill would offer the opportunity for approved dosage reduction.
Sorry, but I don't see how you can do anything dose reduction wise with the tablets. They are the same dose of 100mg and the instructions specifically state not to break or crush the tablets. It's a missed opportunity, but perhaps that would complicate obtaining FDA approval for a lower dose.
Neil
I get my Calquence directly from Astra Zeneca under a special program. It is not available yet through doctor. The company is aware I take half a dose.
I am taking Zanubrutinib at half the recommended dose. Since a regular dose is 2 pills twice a day, I just take 1 pill twice a day with good results. I'm concerned that my disease may be more able to become resistant, but the side effect of fatigue is real for me with this drug. I am left with the "only time will tell" situation.
Do you cut that pill in half?
Don't need to since full dose is 2 pills (capsules) am and pm. I just take 1 capsule am and pm.
But then you do take full dose daily although it is spread out. I take half dose.
No, full dose is 4 capsules per day (2 in am and 2 in pm). I take 2 capsules per day.
Are your capsules/tablets not 100 mg each? If so your 4 a day would equal double the recommended dose. Modifying dosage to just one capsule is recommended by calquence in case if adverse reactions or concomitant medications.
I get the sense that you don’t fully trust your current oncologist. I am not familiar with the health system in Canada, but if it’s possible, I would try to find a doctor that you feel comfortable to work with. It seems to me you are trying to tuneup your treatment without having the expertise necessary. If I was in your situation, I would try to find a doctor I could trust and someone that can answer my questions. This is a very complicated condition and we need to work with competent doctors with the right level of expertise and knowledge about the different treatment options. I hope you can find someone you feel more comfortable working with or at least get a second opinion. Peace 🙏
Thank you for your thoughts. It is very difficult to change doctors here. I have tried.
I am sorry to hear that… It must be very difficult to navigate this condition without a team you trust…
Where in Canada are you?
Where are you located in Canada?
In Toronto
I am in Toronto too. Which doc do you see? I have Dr. Spacer at Sunnybrook.
Sorry, Dr. Spaner
Interesting. What is he like? I saw Dr Spanner a couple of times. He is a clinical scientist at Sunnybrook who offered to take me on as a patient. He spent over half an hour each time with me and explained a lot of the science for me. I said i would stay with St Joe's as it is 5 minutes from my home. But i am thinking of calling Spanner back as i am so fed up with my specialist who spends less than 5 minutes with me and is very dismissive of things other doctors discuss.
I quite like him. He answers my questions. I am on w&w right now, but getting close to treatment after 3 1/2 years. There is also a specialist at Princess Margaret as well, but didn’t want to go downtown. I didn’t know there was one at St. Joe’s. We don’t have many to choose from. Dr. Spaner was suggested to me via this site when I was first diagnosed.
Unless your absolute lymphocyte count (ALC) has been normal or low for a while, there is no rationale for undetectable Measurable Residual Disease (uMRD) testing. My CLL specialist doesn't test until a year or so after numbers have all dropped. So if your lymphocyte count is elevated even slightly, there is no call to do it.
Flow cytometry may be used in these tests, as well as PCR. They range in sensitivity and the prices changes accordingly. uMRD testing isn't needed for everyone.
accc-cancer.org/acccbuzz/bl...
Here's a video by Dr Koffmann if you enjoy watching over reading:
powerfulpatients.org/2019/0...
Thank you for response. My numbers went down quickly 4 years ago and stayed down. But blood tests do not give the detailed information that flow cytometry can. Our government budgeting runs our system which has some big disadvantages. Main one is waiting for appointments. I need a holiday from cardio side effects. But as mentioned I need better insight that MRD measure can give. Possibly full dose can take me towards a better prognosis, or not. Was lucky to get a different doctor in absence of regular one but was not allowed to keep him permanently although he was willing -- as admin makes decisions at that hospital department. I only got the acalabrutinib because I had that one appointment. Otherwise not available and would have had to stay on ibrutinib with worse side effects.
Hmmm if you have time and money, a trip to a US center may get you the testing if you can't get it in Canada. The Adaptive Technologies NGS sequencing one, is what my doc used for uMRD, and it was around $2500. This particular one does require a baseline sample, however. I did a bone barrow biopsy years ago before treatment during a relapse, so my doc had a baseline. Since you are already under treatment, I am not sure if this particular one would be useful. I am not sure what the costs might be, if you can pay out of pocket for other types of testing in Canada.
It's tough when you feel the doc treats you dismissively/won't answer questions. That makes dealing with this so much harder! I hope you are able to find one that you are comfortable with.
I am especially interested in a low MRD...low enough to be considered close to cured...or enough to feel secure in going on a holiday that will last many years.
I think you are misunderstanding what MRD means. MRD may or may not correlate with a "cure". It's just a test saying how many CLL cells there are in a sample of blood. Early MRD tests look at 10,000 cells, newer ones look at a million. So while I am technically uMRD at 12 cells in a million, I am not sure how long it might take for me to have symptoms if I stop medication. I personally have "bad physical symptoms" with relatively low levels of lymphocytes when my variant is growing; others have no physical symptoms at all and only start treatment due to lab values. All it takes is 1 single defective cell hiding in a lymph node somewhere, and the CLL *might* come back. We can't screen or test every lymphocyte cell in our body, and have no way of knowing in advance how aggressively the CLL may grow back, if at all. There are some people here reporting stopping an oral targeted treatment for a surgical procedure, and not re-starting after their doc noticed their CLL wasn't growing after the stop. But there are also reports of people stopping a med and their lymph nodes ballooning within days. I think one will just have to try, and see. There isn't a "number" that positively "correlates" with a long term remission. This disease is extremely heterogenous, people may not react the same.
I am very clear as to the meaning of MRD. The information it gives is more precise and detailed than regular blood tests give. This can be useful in making treatment decisions and planning one's life. Of course one reads the information as it pertains to one's personal situation. No general rules obviously. You already indicate you have more detailed picture of your disease than i have of mine, and its progress or degree of remission. My doctors did not even discover i had it until i was on stage 4, despite various blood tests. I do not want more arrythmia and it's dangers than necessary.
🙏🙏🙏🙏
I started Ibrutinib March of 2019 and Alacabrutinib around June of 2020. I wonder how long this will last. Not looking forward to moving to something else. I am happy with Alacabrutinib.
My CLL specialist said acalabrutinib can be effective for years. I read some articles which stated the average time before problems develop is 4 years.
It's important to differentiate between the median (not average) time a treatment is effective for those for whom their treatment remains effective and those for whom it's their second or later treatment. I'd also argue strongly that there should be a third group - those who are have never been treated with an older chemo treatment, as they are likely to do better. Also, many patients quit ibrutinib because they couldn't manage the side effects. Acalabrutinib is much better tolerated.
Neil
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