Experience with lower dosage of BTK Inhibitors (Ibrutinib, Acalabrutinib, Zanubrutinib)

[MikeOr]

For those who were initially on lower than the stanrdard dosage of BTK inhibitors, what was your longer term trajectory ? Did it work in lower dosage, or you had eventually to bring it up ?

[gardening-girl]

Mike, I didn't start out on a reduced ibrutinib dose, but switched to 280 mg two years into treatment, only after calculating that at my blood volume, estimated to be about 3.5L, the 280 dose should be effective. I've been on the 280 dose now for 5 years.

[LeoPa in reply to gardening-girl]

How do you estimate your blood volume?

[gardening-girl in reply to LeoPa]

There are several blood volume calculators available. This is the one that I used: mdcalc.com/blood-volume-cal...

If you are interested in reading the clinical trial publication on which I based my decision I can try to dig that paper up. Let me know.

[Davidcara in reply to gardening-girl]

What is the dose per blood volume?

[gardening-girl in reply to Davidcara]

Dosages were not actually reported that way. Here are the two papers.Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia New England Journal of Medicine 2013

nejm.org/doi/10.1056/NEJMoa...

and

Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies

Journal of Clinical Oncology 2013

ascopubs.org/doi/10.1200/JC...

[LeoPa in reply to gardening-girl]

Thank you.

[PaulaS Volunteer]

Hi Mike, This is a very relevant question.

I started on the standard dose of 420 mg Ibrutinib daily. After 6 months this was reduced to 280 mg, due to side effects. Side effects improved but not entirely, so after a further 8 months, I reduced to 140 mg Ibru. I’ve been on that for the last 3 years.

All through those reductions in dose, my bloods continued to slowly improve, with no other symptoms that might suggest CLL progression. My ALC hasn’t yet reached normal range, but it’s stable and other things (eg haemoglobin and platelets) are OK. I’d like to see my ALC come into normal range but my haematologist isn’t bothered about it, as long as other things are OK.

I believe more thought needs to be given to people’s weights when deciding on Ibrutinib doses. It’s been said that a dose of 2.5 mg Ibrutinib for every 1 kg body weight is a reasonable daily dose. I weighed only 54 kg when I started, so 140 mg would've been fine for me. It may also depend on prognostic markers and genetic factors, but I suspect some people are getting bigger doses than necessary.

gardening-girl , how did you know that your blood volume was 3.5L? Is blood volume a better way to calculate drug dose than body weight?

Paula

[gardening-girl in reply to PaulaS]

Paula, I used this blood volume calculator: mdcalc.com/blood-volume-cal.... And no, I don't know that blood volume is a better way to calculate dosage, I used it because the very first clinical trial publication reported the concentration of ibrutinib in the blood necessary to inhibit the BTK, and reported doses that resulted in a range of blood concentrations. Using that information I calculated that I could achieve the necessary concentration at a 140mg dose and compromised with my oncologist on the 280 mg dose.

[Jooby59]

I was on full dosage of Venetoclax for about a year but the nausea became unbearable. I then reduced to 300mg for a few months and now been 200g for 4 months and everything still normal. I was having monthly blood tests but as bloods ok he has reverted to every three months.

[Killerv]

Started Ibrutinib 2/14 (3 pills). Down to 2 pills after about 4 years. Down to 1 about a year and a half ago. Blood counts still perfect.

[morepork]

Yes, I'm another one carrying on on 280mg Ibrutinib as the full dose gave intolerable side effects; and I only weigh currently 45 kgs. Like Paula my ALC's have come down to a range which is higher than normal but within a stable pattern (ditto low Ig's and platelets) so haematologist and I feel OK about that. Gone onto 3 monthly tests and phone consults , with yearly face to face probable. 😊

[LeoPa in reply to morepork]

Oh my. 45 kgs that's less than half of what I weigh. You definitely need more pork 😀😉 just kidding. I love the handle.

[Rogerinhorn2015]

started full dose 3mos ., 280, then 70. Have been on 70 for 5years. Normal bloodwork (only low platelets-110). Have maintained & very grateful. Hope the same for all others.

[Hermance]

It worked at a lower dosage, a third of the dose was OK (my weight was 50 kilos) but the side effects were bad enough to warrant discontinuing treatments: neuropathies in both legs, loss of sensitivity in the legs.

[Pogee]

Hey, Mike—After reading the results of the clinical study of ibrutinib, I decided to start on 280mg, which was two years ago. I'm very pleased to say that I haven't had any of the expected side effects, which typically include a high percentage of folks having upper respiratory issues. That was critical to my decision, as in my 79 years I've had COPD, multiple bouts of pneumonia, sleep apnea, and asthma. I also take a daily amount of pure powdered wheatgrass, which has helped keep my platelet levels normal. At the same time, my white blood cell count has dropped from about 79,000 to 17,000. I'm a male, weigh 175 pounds, and think that 280mg has been a perfect dose for me. Good luck to you!

[tola2222]

I started on 280mg Ibrutinib (11q del, Unmutated, Weight 72Kg). Reached U-MRD in less than 3 years. Continued on 140mg maintenance.

[moty3012]

started Ibrutinib 3 pills 10/18. after 2 months blood count jumped to 750,000 and i was hospitalized. dose redced to 2 pills. numbers gone down to 7000-9000 in about 18 months. i had some side effects so i decided to go to 1.5 pills (week 2 pills and week 1 pill) and i am now 9 months on this dose. counts are steady, side effects lesser.

[dooner6]

I started out with IBRUTINIB dose of 560 mg. Wiped my butt so we reduced to 260 and Waldens is fine.

[Lainievrr]

My husband was on 3 tabs a day fir many years and then he needed surgery so he went off ibrutinib for two weeks and when they tested his blood he was in full remission so they decided to leave him off and see what happened... three years later he is still in full remission and not on the meds.... he is enjoying a wonderful life...even recovered from Covid like a healthy person.... there is hope out there with all these amazing meds...

[narl]

Reducing down to one tablet worked just fine for me just to my numbers went down a little slower, but then I had to stop at all together because it caused a fib