Reduced dosing of acalabrutinib

[Savvyman]

I recently reduced my daily dose of acalabrutinib from 200mg to 100mg (half the manufacturer's recommended dose) due to a full body rash I developed during the first month of treatment. In a few weeks, the oncologist is likely to recommend that I return to the full daily dose of 200mg if the rash doesn't come back. Believing that less drugs is better, I'm considering advocating to stay on the reduced dose of 100mg/day if my blood work continues to improve. My question is has anyone reduced their daily dose to 100mg and if so, has your blood work continued to improve? Has anyone seen any kind of evidence that 200mg per day is better than 100mg per day? Thank you!

[cajunjeff]

You ask a good question, here is my layperson take on it. There are much more data on reducing the dose with ibrutinib than there are with acalabrutinib. That data are conflicting, that is, in some studies reducing the ibrutinib dose does not impact outcome and in others reducing dose leads to a worse outcome.

I think the approach for most doctors is to give the full recommended dose so long as its tolerable. Acalabrutinib has already been through clinical trials to determine the optimal dose.

I am sure you can find many people who are on reduced dose of acalabrutinib who are doing fine, and you might do fine as well. The data being inconclusive, its still possible using a reduced dose could lead to resistance and a poorer outcome.

All the top cll doctors, and all good doctors in general, want to use the least amount of medicine necessary to get the job done. I think whenever or if ever the data are conclusive that we can do just as well on a reduced dose, we will all be on reduced doses.

In the meantime I think doctors treat us on a case by case basis. Reducing your dose due to an intolerable side effect makes perfect sense. It makes perfect sense you would not want to risk a rash recurrence by returning to the recommended dose.

I doubt you will get any absolute answers. I would assume that upping the dose creates an unknown risk % of the rash returning and staying at the lower dose creates an unknown risk % that lower dose acalabrutinib will be less effective in treating your cll.

I suspect your doctor has balanced those risks for you and thinks being on a full dose is best for your cll. Its a good discussion for you to have with him.

Here is one of the inconclusive studies I refereed to:

Some studies have shown worse outcomes in patients requiring dose reductions while others have shown no decrease in treatment efficacy [7, 12, 13, 15]. These controversial findings highlight the numerous confounders that potentially impact ibrutinib dose modifications and outcomes, rendering it difficult to draw any definitive dosing recommendations at this time.

jhoonline.biomedcentral.com...

I am on acalabrutinib and would love to be on a reduced dose, but since I am tolerating it well so far I want to stay at the dose proved effective in clinical trials and not take the risk a lower dose would not work as well. If acalabrutinib gave me a bad rash at a higher dose, I would certainly consider a lower dose.

[Savvyman in reply to cajunjeff]

I'm relatively new to this group but I have seen quite a few posts from you. Thank you for taking the time to communicate with others.

I agree that there aren't many absolute answers out there but your opinions are nonetheless valuable. My biggest fear would be developing a resistance to the meds if I stay on a reduced dose. I think I've over the hump in terms of side effects and I'm hoping that my body will continue to adjust to the meds. If so, I'll probably go back on the full dose when recommended by the doc.

Thanks again for your sharing your thoughts Jeff.

[cajunjeff in reply to Savvyman]

You are welcome Savvyman. I think you are making the right decision based on the available data.

It might well be that the data eventually show for certain that we can do just as well on a reduced dose. The standard of care for most top cll doctors as of now, so far as I can see, is to maintain people on the full recommended dose that they can tolerate until the data show less is safe.

And its never a one size fits all thing. My guess is that a doctor might be more inclined to experiment with a dose reduction on a 100 pound woman than a 300 pound man.

[avzuclav in reply to cajunjeff]

I agree about the weight, cajunjeff .

If you want to see why they chose 100mg BID, check out Figure 1-B of this NEJM paper: nejm.org/doi/full/10.1056/N...

acalabrutinib BTK occupancy by dosing

[Justasheet1]

Hawk,

Great reply and great to see you posting again. I hope that you’re feeling well.

Jeff

[Hidden in reply to Justasheet1]

Thanks my friend,

I posted a new thread yesterday

[Savvyman]

Thanks hawkeagle. I hope you found a successful treatment when acalabrutinib stopped working. If I stayed on a half-dose and it was simply less effective, I could live with that, but if half-dosing might make my CLL resistant to acalabrutinib, I might be better off going back to two. Thanks for your advice and good luck on your journey.

[Hidden in reply to Savvyman]

And to you! Best wishes for your treatment!

[spanish36]

I have taken 2x100mg Acalabrutinib capsules daily for 12 months. I have endured any rashes; fortunately. Other than nausea, headaches during my first two months my side effects after that period have proved minimal. The good news is that my relevant blood test readings are now approaching the normal range after being at high levels at my start date. Life is so much better these days. I hope your taking just 100mg daily works for you?

[Savvyman in reply to spanish36]

Thank you for this info. I'm glad to hear that your blood is returning to normal. I'd love to stay on one a day but if there's a chance that by doing so, the medication will lose it's effectiveness, I may return to 2 a day. Thanks again for responding.

[spanish36 in reply to Savvyman]

You are most welcome. I can but add that after 12 months taking 2x100mg Acalabrutinib my daily life is greatly improved. I no longer need to take long rests daily. I have returned to activities such as kayaking, active walking and enjoy going out with friends and family. Life has returned to what it used to be several years ago before my CLL made every day so difficult. I wish you a similar recovery. Cheers.

[Junebug20 in reply to spanish36]

I love reading you have returned to normal activities again. My husband has CLL and started on Acalabrutinib 1 1/2 weeks ago. All his bloodwork is way worse and he can barely function. The headache is now gone. He goes again tomorrow for his second blood draw. It’s good to hear there is a light at the end of the tunnel.

[stevesmith1964]

Personally , discuss with you oncologist,and follow hs direction

[LeoPa]

Is that a theoreticall question or do you have proof that despite the lower dose your blood work keeps improving?

[cajunjeff in reply to LeoPa]

I think if you started everyone on a reduced dose of acalabrutinib, almost everyone would show their labs improving over time.

The question is whether the labs would improve as well as they do on the full dose and if using a reduced dose leads to an earlier or greater chance of developing resistance.

[LeoPa in reply to cajunjeff]

I see. Thank you.

[ClassyLady3]

I have been on 100 mg Acalabrutinib for 7 months, and my blood work continues to improve slowly month by month.

[Savvyman in reply to ClassyLady3]

Thank you for responding. Did the docs start you on the reduced dose of Acalabrutinib or did you reduce from 2/day to 1/day due to reactions? Thanks!

[ClassyLady3 in reply to Savvyman]

I started out on 20g day, but couldn’t tolerate the side effects of muscle spasms. By decreasing ing to 100mg, they are lighter and I can tolerate them.

[skunkbay53]

My husband did 3 months of 2 a day Calquence then started Rituxin infusions. A couple months later he went to 1 a day Calquence. His blood did continue to improve. He has been in a form of remission now for 7 months. Only taking 1 100mg per day

[Savvyman in reply to skunkbay53]

Thank you for this info. Did your husband start Rituxin because the first 3 months of 2 a day Calquence wasn't working adequately or was the switch to Rituxin infusions planned from the start of treatment? Thanks!

[skunkbay53 in reply to Savvyman]

No both treatments were planned out by his hematologist...he planned on the combo treatment

[BaseballGardener]

There are several options on how acalabrutinib is administered. I am familiar with the 100 mg capsule, whereby you take the drug twice per day. There is the same capsule, whereby you take the drug every 24 hours. There is the same capsule, whereby you take the drug 3 times per week (Mon, Wed, Fri, for example). The recommendation is to drink plenty of water, as the destroyed WBC are excreted through the kidneys. My mom had the same reaction you describe: excessive bruising on the arms after 1 month of taking the drug twice per day. After 1 month the drug scheduled was revised to 100 mg/daily. This regimen continued for 10 months. During this time the WBC count was reduced 90%, and the RBC and platelet count started to improve. I agree with your suspicion; if your hematology report continues to improve, then it might be a good idea to stay with the once daily routine. Let the data speak for itself. The bruising may take a long time to diminish, and triamcinolone may be used topically. You should also monitor for any blood in your stools, and have that discussion with your doctor. Every case is unique, of course, and is dependent on many factors (age, other health conditions, etc). There is no magical one answer for all. My mom's doctors were very happy that once daily was the "sweet spot" for my mom. Best Wishes, stay determined, you will win over this disease!

[Savvyman in reply to BaseballGardener]

Thank you for this info. I'm glad to hear that your mom is doing well!