We have not been able to see our regular oncology doctor for a month now. So, when a substitute doctor from Miami (who is a hematologist and oncologist) talked with us....he has decided to reduce my husband's dosage from 420 to 280? My husband's neutrophils have dropped to .8 from 1.3 and 2.3. Does decreasing this dosage help? Will this affect the effacacy of the drug to battling his CLL? (Just wish our regular doctor had been there, but he is on a well deserved vacation and will be going to a conference as well.) BTW...this doctor was horrible in is treatment of us....would not recognize my questions as a caretaker, and spoke in confusing metaphors with my husband. Sigh...
Will reducing Ibrutinib dosage increase neutro... - CLL Support
In my own case, decreasing the ibrutinib (I am now on just 140 mg) did seem to increase my neutrophils. That's why my CLL specialist advised me to reduce my dose (becaue my neutrophls tanked at one point). That's also why he hopes to keep me on that low dose when I undergo chemo-radiation starting in a few weeks. He is hoping that will help me keep my neutrophils at or above 1.0, which is the threshold required for staying on chemo. The chemo and the radiation will suppress my neutrophils. He didn't want the ibrutinib contributing further to that, hence the dose-reduction on the ibrutinib. So all I can say is that some CLL specialists seem to recognize that ibrutinib can lower neutrophils in some patients.
Good luck to you & your husband.
So sorry that you had such a bad experience with the substitute doctor. After a couple of years on 420 mg ibrutinib my dose was reduced to 280 mg several months ago and so far I have experienced no differences in my CBC with WBC differential.
From a common sense point of view, a one size fits all dosage of these powerful medications does not seem right. Should someone who weighs 100 pounds need the same dosage as someone who weigh 200 pounds? Do all people respond the same to a given medication?
There does seem to be lacking some validated guidance from the manufacturers on this subject. This leaves it up to the individual doctor to adjust by trial and error.
Unfortunately, common sense isn't easy to apply with Ibrutinib, because the kind of bonding of the drug within CLL cells isn't the standard, reversible bonding with which research pharmacists have plenty of experience, but irreversible covalent bonding, which is quite rare in pharmaceuticals.
The dosing level used in the CLL trials which led to the FDA approval at that dose, was determined in earlier trials, with the aim of inhibiting CLL progression. For Mantle Cell Lymphoma or Marginal Zone Lymphoma it's even higher at 560 mg orally once a day. While work is now being done to determine if the dose can be safely reduced, particularly in lower weight patients, I gather the initial focus was on trying to ensure maximum occupancy of the drug in new CLL cells before the drug concentration dropped away.
You are right Neil...
Ibrutinib and Zydelig (idelalisib) work to block BCR signals.. so you need enough drug to make the road block. Less drugs do two things, some signal get through in some B cells reducing the effectiveness and this can lead, over time to changes to the attachment point were the road block is set-up... effectively mutation causes total drug failure.
This is different than chemo or immunotherapies that use body mass calculations for drug dosage.
Dr. Sharman has an excellent bit on why maintaining dose is important...
A tiny trial at MDAnderson looked at dosing but haven't published yet...
Dr. Sharman's article was an excellent description. In it he describes the concept of "optimal biologic dose" as separate from "maximum tolerated dose". He cites to need to learn what is the "optimal biologic dose". That was three years ago and yet the question is still unanswered by a rigorous scientific study. And I find it highly unlikely that the drug company is going to fund a study on how you can buy less of their product.
So I suspect doctors are going to continue to trust their instincts and respond to their patients and how they react to the drug. In some cases this might mean dosage reduction. In some cases it may mean an alternative treatment. In all cases, the patients need to follow their doctor's guidance.
Great article Chris. I hope the combination therapies get to first line treatment soon.
Chris, I am running off Dr. Sharman's article and will give it to our doctor when we see him next. Unfortunately, my husband's prescription was up and the substitute doctor prescribed the lower dose and it arrived this week....My husband did not have any real side effects except the falling neutrophils.
I haven't had any problems with my neutrophils, but did have trouble on 420 mg of Imbruvica. Started April 5 and was on for two weeks and experienced a very bad rash. Went off for two weeks, started back at 140 for a week, now up to 280 mg that I'm on now. The 280 will work a little slower, but it does work. I'm anemic and as of Monday with a new blood draw, I'm almost out of the anemic range. My white count and ALC are going down nicely. So, at 280 mg it continues to do the job. Would probably have made more progress by now with the 420, but can't tolerate it. Sorry you had a bad experience with the doctor. Some doctors have big egos and those are the ones I want to kick into next week. My best to you and your husband. Carole
Be careful about reducing the dose to avoid some side effects. I visit Dr. John Bryd at Ohio state, the principle investigator of ibrutinib, and he advised against reducing the dose due to side effect issues. Instead, to deal with my side effect issues he recommended acalabrutinib. And this week the FDA just approved using Ventoclax and Rituximab as an alternative. Can you get a second opionion, but from a CLL expert? have you tried the free second opinion program at cllsociety.org?
Thanks, we do have another CLL specialist at UW Madison Hospital....nationally recognized so we will contact her...this is so distressing at times....
Hi larry...I'm interested in knowing your side effects. What did you experience? Will wait to hear and thanks. Carole
Brittle nails. Muscle and joint pain. Virus activation. Cocksackie virus--mouth sores. Some GI track issues.
I'm on 280 mg of Ibrutinib down from 420 which I couldn't tolerate and have had no side effects like you're describing. I do have some heart rhythm problems that are being looked at by my cardiologist and we don't know if it's the meds or not. Are your neutrophils low? Mine are in the normal range and I haven't had any viruses or mouth sores. I think GI issues are just part of the program for IB. Let me know on your neuts.
Ibrutinib is notorious for triggering afib. Acalabrutinib has been prescribed to treat cll patients who have had probs with ibrutinib. Currently acalab... isn't FDA approved for my cll situation but my insurance company blessed the Rx my doc wrote. I am traveling and can't get to my labs until the end of next week so I can't give you the neutrophil data.
I wore a heart monitor for 48 hours last weekend and I don't have A-Fib, but the doctor doesn't know what is causing my terrible irregular beats. Will be having two more tests this week, then wear a monitor for 30 days. If nothing shows with those tests I may need a change of meds.
Dr Keating from Anderson recommends 2.5 mg per kilogram body weight. Good luck
Can you translate that? My husband weighs 192 pounds.
Check with Dr.Keating via. Patient Power.Do not change on your own all ways consult with YOUR Dr. Stay healthy.
I was put onto the maximum dose from day one. At the time of starting I had already had 0.00 nutrophils with platelets at 5. Having suffered sepsis 6 times in 8 months following trying venetoclax this was seen as my only option. I weigh 8 stone but despite a few side effects my nutrophils and platelets actually started to recover after a month. Now 4 months in my nutrophils are at 5.60 and platelets 200. I’m still struggling with HP and need weekly transfusions I am home and feeling positive. I know there are many out there who have had a good result from venetoclax but it wasn’t the right drug for me however maybe Ibrutinib is my best match for now and the higher dosage did the trick.
Looking forward my specialist will consider car t when I am stronger.
Hopefully your husband will find the right fit for him to very soon.
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