I have been following so many posts about Ibrutinib before I take this drug next week & I want to thank everyone for their contributions which are so helpful & informative.
But I have now have two main concerns which I need advice on please.
1) I have read about the reduced dosage issues & as a 72 year old female weighing only 98lbs the dosage of 420grams seems rather high for a small body, especially as I don’t have swollen lymph’s, spleen, night sweats etc
2) There are so many positive comments about Ibrutinib which talk about their symptoms of CLL being cleared & either have no side effects of the drug or the side effects are more manageable than the original symptoms so Ibrutinib is good for them.
For me, I don’t have any symptoms so my quality of life is good, (apart from continually rising WBC which doesn’t affect me at the moment but will do at some time soon)
So I’m concerned that living on this strong drug, with possible side effects, is not right for me.
I shall be bringing this up with my consultant on Monday but I should be grateful for any input.
Thanks
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Benny12
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Hi i am on Ibruitinib 13 months in on Flair trial. It is my understanding that they do not take weight or height into consideration as they do with chemotherapy.I am only 4’ 10” and I take the full dose.
Like you I had no symptoms at all apart from low platelets and haemoglobin,indicators for treatment, when they drop too far, which they did in my case. I found it hard to accept treatment as I felt fit and well too. However it has been good for me I have reached a very good partial remission and 🤞hope for full remission which I believe is rare on ibrutinib. I have had many side effects but non of the major ones, all of which are intermittent and manageable so far. Keep us updated.
I am also only 5’ and slight. That was a question I raised with my consultant as chemo and IVIG are weight based so it seemed odd. I was told I should keep with the full dose for present ! I have only had minimal side effects and hopefully so will you.
There are some papers that suggest that a dose of 2.5 MG/Kg body weight attains a similar level of BTK occupancy as the full dose of 420mg of ibrutinib. Hence, it is not uncommon to see patients that are taking 280 and even 140 mg.
To my knowledge there are no papers on dose vs PFS outcomes yet. It is my understanding that many doctors start there patients at 420 mg for a few weeks and then reduce the dose onwards.
I would expect that a lower dose will have fewer or less marked AE. However, it is unclear whether lowering the dose will maintain clinical effectiveness. Some pharmacodynamics studies suggest that the lower doses indicated above may work for some patients.
See a CLL focused specialist, as opposed to a general hematologist. Many hematologists are not well informed about either novel treatments or recent results from either randomized or observational trials.
Google clinicaltrials.gov and find out about dose-response studies.
I am not a medical doctor, so please take these statements with caution.
I think you will do just fine. I am 77 years old and weigh just a tad more then you at 115. I have been on Imbruvica since January 5h with very few very mild side effects. My bad numbers are coming down and the too low numbers are slowly rising. I am very pleased, happy and humbled to be on Imbruvica 420. Please keep us updated on your journey. All the very best to you.
Hi Benny12. Speaking as one of the dose-reduced patients, I think it's important to start at full dose and do your best to stay there for at least 30 days - longer if you have no problems with it of course. Many many people are on full dose ibrutinib and doing fine. I have read elsewhere (and I think been told by my doctors) of the importance of the first month or 2 on ibrutinib. But after that... if you are really having difficulties, you can always discuss dose reduction with your doctor... and ultimately do whatever you truly think is best. It's your body, after all. Just remember that side effects you may experience with start of ibrutunib treatment will often reduce or go away with a little time.
What were your doctor's reasons for starting you on ibrutinib? Usually rising lymphocytes alone isn't enough to trigger treatment.
Thank you for your input Kim. I thought there must be a timeframe initially to keep on with it so that’s good to hear.
I’ve already had FCR, & R Bendamustine (2 cycles)& my lymphocytes are doubling again after 3 years. My new consultant is very keen on Ibrutinib. I’ve pressed for Bendamustine again but i can’t have it unless I pay.
I’ve decided to go with Ibrutinib as I’ve read so many good things about it on this site. I could wait a while but it would only be months & I travel a lot in winter so I want to get started now & see what happens.
I don’t want to let it get to the position I was in 9years ago ,when first diagnosed, when I was rushed to hospital & had two blood transfusions followed by chemo.
You are wise not to wait until things get worse! I too had gotten into a very progressed condition (transfusion dependent) before starting treatment. Good luck with the ibrutinib.
The thing is that chemotherapy often becomes less and less effective the more times you take it (perhaps due to clonal evolution). How many years of remission did you have after the first and second treatments?
nowadays I think most cll experts would not want to give chemotherapy more than once or perhaps twice if there was a very long remission after the first time (and maybe not even then). You are certainly not being given an atypical piece of advice. If you don’t see a CLL specialist you could always get a second opinion from one to discuss your own particular case.
Thank you Adrian. Yes I did think about getting a second opinion but I’ve decided to give Ibrutinib a try for now. It is unfortunate that after 9 years my original CLL consultant retired & I have a new one now who doesn’t know me & at first wound me up & I couldn’t relate to at all. It’s a bit better now after a long discussion.
I have been unusually treated in the past. FCR to begin with. 3 years remission, then one cycle of RBendamustine. 3 years remission & one more cycle of RBendamustine. Now another 3 years have past. So, so far it’s followed a pattern with my WBC rising virtually at the same rate in all the three 3 year periods.
It is actually an abstract from ASH 2018. Briefly, the authors conclude:
"These PK/PD [phamarcokynetic/pharmacodynamic] data demonstrate that after 1 cycle of ibrutinib at the standard 420 mg/d dose, the dose can be reduced without losing biological activity. Clinical efficacy of lower doses needs to be systematically evaluated. Such dose reductions would lower drug cost, lessen untoward toxicity, and facilitate rationale-based combinations."
I started Imbruvica at the full 420 some 3 years ago. My CLL-related blood numbers immediately improved, but after 3 months of fairly severe side-effects, my Hema. agreed to a dose reduction (to 280). My CLL #'s continued to improve every month, and the side-effects abated quite a bit. There was no dosage study at that time, but 280 seemed to work fine for me. Thus, this "case study of one" would recommend (note - no medical degree here) that you start at full dose, then reduce it if problems occur.
WARNING, however: After 15 months, I developed Afib and mitral valve damage, so watch for it, and get periodic EKG's - Afib does happen in about 15% of Imbruvica cases. But, for CLL, 240 worked for me.
Gary how did you discover you had developed Afib? Were there symptoms? I have been on ibrutinib for 19 months (dose reduced most of that time). I have often wondered if I would even be aware if Afib was developing.
The honest answer is that I had a pacemaker installed 8 years ago for a totally unrelated incident. It sent periodic reports to my cardiologist, who called me one day and said that I'd been in Afib for over a month. I visited her, and both a download of my pacemaker info and an EKG verified it.
However, as I said, I've thought about it, searched the Internet some, and asked my doc. Results: you might be able to hear or feel something "a little off" in your chest, especially at night, and if you're cognizant of the possibility. Much better, though (it seems to me), would be to either take your own pulse, or have a partner or friend do it. Afib races your heart about a hundred miles an hour, so it's easy to spot, IF you're having an episode (you'll often get it for only a few seconds or minutes- especially at first; that's not a problem, but mine continued over 2-3 months to become continuous; that's not good).
Hope this helps! And, ask your doc - he/she may have a better idea (although my docs rec to "get an EKG" seems like it could get pretty expensive after a while).
Thanks Gary. It seems to me an EKG won't be useful unless Afib is manifesting at the moment the EKG is done. I guess that's why they send people out with holter monitors for a 24-hour period...
Quite relevant to this discussion is Dr Rick Furman's update on this topic today on the CLL/SLL Groups.io community, of which I have quoted his analysis of the mean Ibrutinib levels at 420, 280 and 140 mg. Note Dr Furman's concerns about 140mg dosing.
"The IC50 for ibrutinib on BTK is 0.5 nM. (There are many differences between cell free and non-cell free assaying. The 0.5 nM is cell free, so the likely needed concentration is going to be higher.) In the paper, the authors cite the mean ibrutinib levels were 22, 22, and 8 nM for 420 mg, 280 mg, and 140 mg respectively. The authors show, in the nine patients they studied, that the 280 mg and 420 mg doses did not achieve different concentrations in the blood. This would support the fact that for these 9 patients, 280 mg was sufficient. But at the lowest dose there was a very significant fall off of the mean serum levels, and thus everything depends upon whether the 8 nM is still sufficient to inhibit BTK. This is also the mean, and we don't know what the time of exposure that is required to achieve full inhibition.
With this being said, it seems worrisome to take a chance with dosing a drug that is potentially saving one's life. The authors publish on flat dosing without including patient weight, so it is not possible to generalize these data. We do believe subtherapeutic dosing is a recipe for developing resistance. It would seem prudent to me to follow recommend guidelines, that are proven effective and only dose reduce for toxicities, which are, in essence, and clinical read out of dose level.
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