Apparently the Ibrutinib worked so well that my spleen had literally shrunk in days.The only problem was the WBC count going up to 1000s causing my skin to go into stress.Large bruises, petechiae all over body and rash.My platlets dropped from 70 into the 40s and the headache and blurred vision was getting worse by day 12. Went to hospital for emergency ct scan. All good. Had a blood transfusion, platlets up to 110.My rbc still can't be measured due to the WBC in blood stream.The 7 days on predazone helped my skin calm down completely. Feeling like myself again and ready to deal with this.
Dr gave me two choices.
1. To have one round of chemotherapy and continue with Ibrutinib 140mg three times a week.
2.Start back on Ibrutinib 140mg three times a week.
I picked plan 2. Slow and easy.If I'm truly allergic to the drug I feel that I'll know.I believe this drug could work for me.
Thanks for letting me rant.
Miller1960
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Miller1960
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I’m sorry to hear about your complications with Ibrutinib.
Good to hear that things have calmed down at the moment,
Re plans for going forward, I can understand why you chose the second option the doctor gave you – in your position I think I’d have done the same. It’s very hard when doctors themselves don’t know which might be the best choice.
I started with three 140mg capsules of Ibrutinib daily, and had a lot of side effects. (Mostly joint problems, though my platelets stayed OK). After about 2 months, the worst of the side effects went by themselves, but later others came – including rashes.
I stuck it out for 6 months, then reduced the dose to 2 capsules. Things improved, but the stomach problems continued. 15 months after starting the Ibru, my doctor agreed that I could reduce to 1 capsule daily. My stomach pains eased from then onwards. Such a relief. My lymphocyte count is still not back to normal range but at least it’s still going in the right direction. (It rose to over 600 thousand after starting the ibrutinib, and is down to 43 thousand now.)
People’s experiences vary greatly, on ibrutinib. It seems to be a very unpredictable drug, but often the worst of side effects do wear off with time. I do hope that will be the case for you.
Thanks for the feedback. A powerful and amazing drug that effects people differently. I'm surprised a person's size doesn't influence the dose. I'm 5ft. and weigh 112lbs.
Read this post for the viewpoints of Dr Furman, who was strongly involved in the Ibrutinib clinical trials and has used Ibrutinib extensively since then, with dose reductions where practical:
I've read Dr Furman's article and hear his statement that "Subtherapeutic dosing will likely lead to resistance, which is of no value to anyone. I implore everyone to not take chances with their health."
However, it appears that some people may be getting much MORE than the therapeutic doses of Ibrutinib for their particular size/shape. This can also be causing problems for their health, which need to be taken seriously.
It's all very complicated and I hope more research is being done, on best doses for different people. Ibrutinib is a very powerful drug and not yet fully understood.
I agree, but note that even Dr. Furman admitted that he adjusts doses:
"I do dose reduce patients frequently, but always remain safely above the 2.5 mg/kg dose."
The original paper, which had Dr. Michael Keating's name on it, by the way, concerned a tiny, pilot study of only 14 patients. The danger is that patients would read it, and reduce dose to save money or avoid side effects without doing the dosage calculations that a doctor should, and without consulting their doctor. This is especially a danger in the U.S., where we have failed to convert to the metric system as a society, and where older people don't regularly do the math.
lbs kg 2.5g/kg/day 5g/kg/day
100 45 112mg 225mg
200 90 225mg 450mg
300 135 337mg 675mg
Dr. Furman cites the higher 5mg/kg for margin of safety to assure that all B-cells will bind. Since we now know that some ibrutinib binds to other types of cells, this margin is especially important, I think.
I would add that large, heavy weight people may actually be under-dosed at 420mg/day. I presume that oncologists do make the calculation, and do not mindlessly give the 420 dose to such people.
As I recall, there was also controversy regarding pricing of the doses, where allegations of gouging were made against Janssen (Johnson&Johnson) and Pharmacyclics (AbbVie) when they announced intention to eliminate the 140mg tablet:
My take is that in light of the side effects in a percentage of patients, the manufacturers could provide even smaller doses that could be added up to attempt to avoid those side effects by aiming at the 5mg/kg target. I really don't understand why this isn't done - it's done for so many other therapies.
My haematologist said he is generally reluctant to reduce the dose , but as I'm not very big ( 5 ft.4 inches and weigh 118 lbs.) he was happy for me to reduce.
As time passes and more data collected, I hope Ibrutinib doses will be more adjusted to suit different individuals.
Yes, a lower dose for a smaller person makes sense to me. It seems reasonable that the dosage could be adjusted for the weight and size of the person. The question of equal dosage for a 200 pound person and a 120 pound person seems questionable and taking into account the severe side effects. I hope I can convince the hematologist to start me on 120-140 mg a few times a week rather than the hefty dose of 280 mgs.
Yup! Look up my prior posts. After one week on Ibrutinib my left hand swelled to size of boxing glove - 9 days in hospital. No treatment x 6 months - lymph nodes exacerbated - MD said you are dying of CLL so we agreed to try Ibrutinib at 140mg 3 days a week which was good so in a few months went to 140 mg 4 days and 280 mg 43days. Have side effects , of course, but nodes negative, counts good so far after a couple of years. Best to you. MC
So good to hear that the lower dose was the path to improvement for you. I hope to start with a lower dose so I can avoid or at least minimize some of the side effects. So happy your counts good after a couple of years. These posts are so helpful.
Sorry to hear that Miller. I'd keep an eye on the Canadian approval process. You also might call Astra Zenica and see if you can get it without charge. I don't know if they'll do that outside of the U.S.
I would have also chosen your option #2. From what I've read if the FCR doesn't completely wipe out the CLL it can become mutated and much harder to treat.
I guess Venetoclax + Rituxamab is also not available in Canada yet.
I had a really uncomfortable blistering rash on IB for 5 months, even when I reduced dose and even stopped it for a while. The skin doctor they sent me to couldn't diagnose it. I've been on Acalabrutinib for 6 months and have only had one minor outbreak (which Prednisone stopped immediately) and may have been related to a very bad cold I had just before. It's slower at reducing lymphocyte count but my ALC and platelet counts are still heading the right direction.
Comparison of acalabrutinib, a selective Bruton tyrosine kinase inhibitor, with ibrutinib in chronic lymphocytic leukemia cells
The gist is that ibrutinib matches off-target signal proteins on some other cell types, and acalabrutinib less so. So, acalabrutinib is more specific to B-cells than ibrutinib is.
Even so, acalabrutinib may still bind to some other cells, I suspect.
Thank you, Miller1960, for your post opening up the discussion of lower dose Ibrutinib. I have wondered if I could start with a lower dose of Ibrutinib when I begin on June 10th. I like your comment of "slow and easy". I am concerned that the regular dosage will not address the reasons the hematologist is so insistent that I start treatment. The last blood tests have shown diminishing hemoglobin and platelet numbers but ibrutinib sometimes reduces the hemoglobin and platelet numbers so how is that helpful? As well, my fatigue is extreme and ibrutinib, I've read here, also has an extreme fatigue side effect. I'm so needing treatment but if it makes me worse with some important health issues, what will happen to me...
2) When treatment is started, how do we ensure CLL is controlled and not given the opportunity to develop into an even harder sub-clone to treat?
Treatment guidelines include an allowance for the dip in blood counts that often occurs. Guidelines in Australia for platelet transfusions are under 20(thousand) if you have a fever and 10(thousand) if otherwise well. That's a long way below the treatment trigger count of under 100(thousand). Likewise, haemoglobin needs to fall below 6(0) before you risk organ damage (but you won't be thinking/feeling well before then).
1. I have a strong treatment aversion, most pronounced when I was pressured to take a chemo therapy. I refused because of the devastation I saw with the husband of a dear friend. Sadly, he passed away.
However, I am now tired of being tired and I know that I must begin some treatment with the hope that I will experience some relief from swollen lymph nodes, fatigue and falling hemoglobin and platelets and other unhealthy numbers. Hematologist would prefer if I start treatment immediately but has given me 2 months to have the 2 week blood test numbers watched, as well as give me an opportunity to research ibrutinib. Another blood test Monday. I also am dealing with infected mosquito bites and an extreme allergic reaction to the bites such as swelling.
So I feel like I am now boxed in... treatment or more of this unsatisfactory living situation. I'm almost ready to say ok, let's do this.
2. I wish I was as informed as you and other commenters but I have relied on research papers. However, I have learned more about treatment options from this excellent blog. I'm not much of a blogger so I have to learn how to ask questions and respond.
The comment you made re: "When treatment is started, how do we ensure CLL is controlled and not given the opportunity to develop into an even harder sub-clone to treat?" has me wondering if I understand about sub-clone development. I remember reading a comment about how ibrutinib developed into a different blood cancer and then chemo was needed. I would not want that to happen. I want to minimize the side effects and since I am at the lower end of physical size that it would make sense to start with a lower dose. Now I have to convince my hematologist. When I asked what would happen if some serious side effects occurred, he off handedly said, well we'll just find something else. Here, I have learned what some of the something else could be. I am impressed how brave the posters are here with treatment decisions and adjustments and handling side effects and other health situations. I feel like I need to be dragged to treatment. I want to be sure of everything but am discovering that the drugs manufactures don't know everything... such as dosage. Isn't that one of the standards that need to be researched before drugs are offered to patients. It just couln't be a one size fits all. Ah, well, now I'm ranting a bit.
Chemotherapy for CLL isn't as bad as for other cancers. People don't lose their hair, but some experience thinning. There hasn't been a new chemo treatment for CLL developed in ages. All the new treatments are non-chemo, targeted therapies.
There's what's known as an optimum treatment window and from your specialist's recommendation, I'd say you are at the sweet spot now. It's a bit of an art predicting it, but ideally you don't want your tumor burden and your bone marrow infiltration to get too high, or you increase the likelihood of having a rougher time with treatment.
Dosage IS determined during trials - by the brave souls in phase 1. As experience is gained from more patients, then it becomes clearer if one dose doesn't fit all.
Clonal evolution is simply the process by which DNA copy errors creep in as cancer cells divide. If the DNA errors provide a selective advantage to a given subclone, it becomes dominant as the other clones are killed off by the treatment. If is unable to be controlled by the treatment (your CLL has become resistant), then the solution is indeed to switch treatment drugs. Obviously it is best to avoid this happening. With CLL still incurable, we need to obtain as long a remission/control as possible to stay ahead of clone development.
This is why it can be very dangerous to reduce the treatment dose. You want to maintain a sufficiently high blood serum level to kill CLL cells so they don't get the opportunity to divide and develop tougher to treat CLL.
Thank you, again for your patience and knowledge in replying to my comments.
1. I think it's reasonable and medically prudent to reduce the dosage because of my weight. Would you agree? However, what is the magic number? I definitely do not want to have any mutations develop to create even more complexity to treatment.
2. I don't want to overload my body with the Ibrutinib treatment whereby I am incapacitated by a range of serious side effects. I am hoping for an increase in quality of life not a slide down to who knows what... my greatest fear is agreeing to Ibrutinib treatment and then serious side effects necessitate experimentation for some drug that will mitigate the side effects. Then I will have lost autonomy.
I'll read again the article you posted re: dosage. I've learned so much by reading this blog...
Have a wonderful last days of May... loving the spring that finally arrived here and the spring fragrances.
The 'magic number' used in setting the dose used in the trial that resulted in FDA approval for CLL/SLL was 2.5mg per kg of body weight. Note that the trial for Mantle Cell Lymphoma used 560mg compared to the 420mg used for CLL. You need to discuss whether dose reduction is prudent with your specialist, but personally, if I had access to Ibrutinib, I'd want to get my tumour burden way down before experimenting with dose reductions IF I was experiencing concerning side effects.
When you read through posts from members taking Ibrutinib, keep thought uppermost that people doing well on Ibrutinib don't post to share that - it's people who wonder if Ibrutinib is causing side effects. We have occasional posts where members on Ibrutinib with little to no side effects reply in response to members asking for experiences. Unfortunately you won't know if you fall into that category until you try it.
I would say we lose autonomy to varying degrees when we learn we have CLL. While most of us then have to come to terms with the stress of living with watch and wait, that still has to be preferable to being told we have to start treatment immediately, which does happen to some of us and to those diagnosed with acute leukaemias.
At least through this forum, we have the opportunity to regain our autonomy through learning about our illness and how best to treat it. Remember that many of us don't have access to Ibrutinib, with chemo our only option, even if we are unmutated IgHV - and we can't even get that tested!
Thank you for putting the CLL challenges in perspective.
I didn't know that Ibrutinib is not available to everyone!
Would you elaborate a little about what you said, "... I'd want to get my tumour burden way down before experimenting with dose reductions IF I was experiencing concerning side effects." When I think of CLL, I have never thought about the cancer cells being tumours.
Agree with your statement about losing autonomy with the CLL diagnosis and gaining some autonomy with learning about CLL. I used to read research papers but this blog brings CLL home where reality hits the road. When I was on w&w, as long as I felt relatively well, I never thought about it, except for 3 month check ins. As energy lowered which was sometimes difficult, I adjusted, it was the unexpected severe mosquito allergy effects that threw me for a loop and everything changed as I lost weight and the reality of my worsening CLL changed everything... wake up call!
Now with the dire warnings from the specialist that I must get treatment if not now, soon depending on the numbers, I must lose my autonomy and give in to the treatment that is being offered. Scary for me... yes! The unknown effects... Giving myself the best chance to limit life challenging side effects. Hence, the last autonomy straw I'm holding on to... the dosage decision. I'll get weighed tomorrow when I do the blood test, or I might have to go to my family doctor who is treating the mosquito bite infection. Then I can calculate the dosage and bring that info for my June 10th appointment.
I have noticed a few posts where a person will talk about that they are experiencing little to no side effects, but the majority of posts are talking about the side effects and the challenges in dealing with them.
I'm using the word tumour in the sense of "A new growth of abnormal tissue that is often uncontrolled and progressive". CLL doesn't form solid tumours, (lymph nodes grow dive to infiltration), but we do have a mass of abnormal CLL cells that can cause what is medically termed Tumour Lysis Syndrome (TLS) if our tumour burden is bad enough, particularly when treatments are very quickly effective. TLS occurs when the massive die off of CLL cells overwhelms our body's ability to deal with the released cellular components and can be fatal if uncontrolled. Allopurinol is prescribed to alleviate the risk.
In my opinion, you are severely and dangerously restricting your degree of autonomy in only focusing on Ibrutinib dose. You have access to a very effective drug that many in our community just don't have and would very, very much prefer compared to what limited choice they have - old chemo drugs. You have access to a huge amount of feedback of tips of how and when to take Ibrutinib to minimise potential side effects (night seems to work best for some, morning for others), along with many, many more tips on how to minimise bothersome side effects, if you actually experience them.
With regard to posts about side effects, when did you last contact your doctor to say how well what they prescribed worked? Ever rung a company to tell them how happy you are with a service or product? If you have, what's your ratio of complaints to complements?
Excellent reply re: tumour load. So much to still learn about!!
Yes, so true about being vocal about problems not about effectiveness or good products. I guess I just expect good products and only voice concerns when they aren't good.
I'm concerned about TLS because I have read where some trials were stopped because of rapid die off of cells and some subjects succumbed to the overload. Another scary side effect but this time of extreme effectiveness. Good to read that there is an "antidote". I will have to make copious notes to include everything I'm learning. The hematologist will not be pleased with my new concerns.
Are CLL patients in treatment expected to hand over our lives without questioning?
I seem to be a CLL patient to the exclusion of everything I have loved to do...
Thank you again for your patience with my processing the impending treatment. I must be thankful for having the option of Ibrutinib? Why isn't it available where you live and will it be coming soon as a treatment option?
The TLS deaths occurred during the dose escalation phase of the Venetoclax clinical trial. The trial was temporarily halted until a more cautious protocol with hospital monitoring of at risk of TLS patients was implemented, which successfully prevented further deaths. Those trial patients gave their lives so others with CLL could be treated without having to worry about being given a life threatening dose of what has become recognised as an extremely potent treatment option. Venetoclax in combination with other drugs currently under trial, has a high probability of providing a cure or very long remission from non-chemo, time limited treatment.
Some doctors might prefer unquestioning acceptance of advice, but I think that more astute doctors appreciate that questioning patients wish to better understand the whys of their doctor's advice and are far more likely to follow it, resulting in a better outcome for the patient and greater success rate treatment statistics for them.
Ibrutinib (prior to any negotiated discount), costs around US$150,000 per year indefinitely. It's a maintenance drug. FCR in comparison costs about $US50,000 for 6 months treatment. Countries providing universal health care are understandably reluctant to allocate taxpayer funds towards a treatment option that costs so much extra for limited benefit. About 30% of those eligible for FCR experience very long remissions, arguably a cure (or about 60% if only given to those with IgHV mutated. CLL. Perhaps 15% of those on Ibrutinib reach minimal residual disease after 5 years and we don't know how long a remission will last if they stop treatment.
The TLS reference is now clarified. There is a wealth of knowledge here! So grateful that answers to all our questions are so thoughtfully and precisely given. More to follow...
Firstly, thank you AussieNeil for this conversation as it was a big part of my process to accept treatment. My fatigue overtook my ability to continue with continuing the discussion. I eventually hit the wall with my extreme fatigue and taking your information, Neil, gave me the confidence to ask to start with a lower dose. Which I did supported by info from you, Neil. I have completed my third 11th day with:
- one 140mg capsule of Ibrutinib which I take before bed
To mitigate potential side effects:
- one low dose BP meds Sivem-amlodipine 5 mg tab in the morning
- one Apo-Allopurinol 300mg tab in the early afternoon (for kidney function)
- must drink 2-3 liters of water/day (for kidney function)
- no coffee
- weekly blood test
Day 3: lymph nodes on the side of my face, etc. shrinking
Day 7: Suddenly a hip bone pain that completely incapacitated, couldn't walk, move, etc. I'm allowed Tylenol extra strength, max 30oomg. Gradually, on the 4th day of this bone pain, I began to be able to limp around. For the entire time, I could only sleep sitting up. I still need 1 Tylenol to go to sleep. This was overwhelming!
Day 12: some nose bleeding but didn't last long.
I still feel this is a gentle regime that doesn't scare me although I was tested by the bone pain experience.
Petechiae on left arm.
I will be on this dosage until the end of July at which time a review of results and possible increase in Ibrutinib dosage....
Before the Ibrutinib and continuing with the approval of Hematologist, I took/take daily dose of 2 Magnesium Citrate 150mg for leg cramps, 4 Vitamin D3 400IU (usually take 2000IU) and 1 Vitamin B12 100mcg
I have much hope for the fatigue to be gone. It feels as if it is lessening. I am willing to weather some side effects to have my energy back... to go for walks, to garden, to be active with grandchildren.
I am in a trial that included 6 months of FCR along with 420 mg of ibrutinib daily. I began treatment in August of 2015 with ibrutinib taken for a week or two prior to the first round of chemo. Within 3 days of my first dose, the lymph nodes in my abdomen had shrunken considerably, I lost 2-3 inches in my waistline overnight(I started out with a cluster that was 8" x 3"). The trial originally had us on ibrutinib for life, but after 2 years of 0 MRD, I was given the option to discontinue Ibrutinib (that was about 1 1/2 years ago). According to the 2.5 mg/kg calculation, I should have only had to take 1 pill a day instead of the 3. I didn't have any really bad reaction to ibrutinib when I was taking it, but now am having a lot of joint/muscle pains/cramping. I've read that the excess ibrutinib can bind to other things, and wonder if it's accumulated in my body and is causing these weird, sometimes debilitating, pains. I'm thankful to be in remission, but hopeful that I can be more active again.
Ibrutinib only has a short half live in the body, which is why you need to take it daily to maintain control of your CLL, not every other day or weekly, for example. It doesn't accumulate, so I would suggest that there is another cause. I hope you can discover and resolve that cause.
WOW! You guys amaze me more and more every day with your knowledge of CLL. I took Imbruvica for a year, with good results - however my one. reduced the dose to 280 after only 1-2 months of most every side-effect listed on the label. My MD may have known, but I had never seen the "2.5mg/kg" guideline. Using it, and my weight, the dosage reduction fit nicely - and greatly reduced the side-effects.
I'm no doctor, and each of us reacts differently, but I'd certainly discuss a dose reduction with him. Somebody earlier said something like, "I can't believe that one dose fits all". The 2.5mg/kg resolves this, why not use it (but ALWAYS discuss with your doc)?
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5 months on Ibrutinib with side effects
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