I’m looking for some experiences please about taking an ibrutinib holiday. I see there have been some posts about clinical trials either stopping or reducing days it’s taken. I would really appreciate any feed back.
My story is I’ve got really good bloods now and have been taking ibrutinib for 4 years, and what a miracle it’s been. I quickly reduced my dosage to one a day due to sore joints. It’s been fine but lately the aches have returned so I’d like to trial adjusting my dosage to one every other day. I saw my specialist at the hospital last week but didn’t have this possibility to suggest trying and also because it’s not funded in New Zealand the specialist doesn’t prescribe it so experience is limited. I initially got it through a private specialist who also didn’t really know a lot about the medication, for example he didn’t believe ibrutinib would cause joint pains and was cynical about one a day. Thanking you Wendy
Written by
Zoethedog
To view profiles and participate in discussions please or .
I see that you aren't really talking about a drug holiday, but further reducing your ibrutinib dose to alternate days. Theoretically, that will increase the risk of your CLL developing a BTKi resistant sub-clone, because there may not be enough BTKi in your system to inhibit CLL cells from dividing and the daughter CLL cells ending up with DNA damage that allows them to escape inhibition. You are approaching the median time for when people become resistant to a BTKi and going to alternate days of a reduced dose of ibrutinib might just hasten that happening - we really don't know.
With respect of drug holiday, as Jeff / Justasheet1 noted, you need expert advice before considering that and to be honest, experts are still gathering data so that they can provide advice to patients who are seeking a drug holiday from maintenance therapy. Your situation is further complicated because in countries with universal health care, prognostic testing is only done prior to starting treatment when it can be used to guide treatment choice. I couldn't see any mention of prognostic testing in your past posts and bio, but you seem to have had fairly stable CLL (~14 years in watch and wait). What we don't know is whether your CLL changed back in 2019 due to the emergence of a tougher to keep under control sub-clone, perhaps with TP53 or 17p del, for example.
Because prognostic test results can change (with the exception of IGHV mutation status), it's only considered a nice to know for the patient When that treatment choice is lacking, the testing usually doesn't get done either. The challenge with ending BTKi maintenance therapy is that even after 4 years, if you have the wrong prognostic factors, as soon as your CLL is no longer inhibited by the BTKi, it's possible to have tumor flare, when CLL comes back with a vengeance - so much so that it takes biopsy assessment by CLL specialists familiar with Richter's Transformation (RT) to determine whether or not the tumour flare is RT.
The other options that you might want to explore, is taking venetoclax to get you into uMRD status, or switching to a second generation BTKi which have lower side effect profiles. There zanubrutinib/Brukinsa would be the best option to you, because it can be taken once per day and dose reduction is easier than with acalabrutinib. Again, you are into unknown territory. If you do decide to pursue this with your doctors, I'd recommend more frequent blood testing and having enough BTKi on hand, so that you can hopefully quickly get your CLL back under control.
Neil I am very grateful for all your input here, thank you so much. I will heed your and Jeff’s advice. And just accept I’m in a hospital situation that has its limitations around what our national drug funder funds. There are other hospitals in N Z who are better up with the play, mine isn’t and I’ll just need to suck it up !!!
Again thank you for spending the time to inform me, and I’m taking your advice.
Neil, I always try to glean what ever I can from your posts. So, when you say she's reaching the median time for resistance to ibrutinib, is this the median time for front line treatment as well as second line treatment?
Skyshark is more in touch with the statistics, but yes, those on early ibrutinib trials had been previously treated and we get longer remissions after our first treatment than in subsequent treatments, due to resistance developing in sub-clones. Of note, some on the early ibrutinib trials are now into their second decade of treatment. Also, a significant percentage of ibrutinib trial participants dropped out not because ibrutinib wasn't controlling their CLL, but because they couldn't stand the side effects. The second generation BTKi drugs have much better long term acceptance with their significantly lower side effect profile.
ELEVATE_TN trial of Acalabrutinib for Treatment Naive has an overall PFS of 72% at 60 months (was 80% at 42 months). There is a distinct gap opening up between A monotherapy and A+O. PFS for A+O at 60 months is now 84%, unfortunately it's not for everyone, all the gain is for TP53 wildtype (IgHV mCLL/uCLL not shown).
ASCEND trial of Acalabrutinib for R/R (relapsed/refractory) has an overall PFS of 62% at 42 months.
At first look it appears that BTKi has about half the time to progression in R/R patients compared to first line. ELEVATE_TN had 33% mCLL while ASCEND has 16%. TP53/17p aberrations were 13% in ELEVATE_TN and 28% in ASCEND. This reduction in the "easy to treat" mCLL and increase in "difficult to treat" TP53/17p makes the results appear worse for BTKi R/R. The R/R cohorts will self preselect patients with a bias to those that failed to reach median on prior treatment(s 1-9), it should come as no surprise that they continue to have shorter times to progression. It's quite probable that R/R trials results will be close to the median of the 50% that failed to reach median.
Two reports from ASH this year are some of the first that start to answer the question "What order should we use the novel treatments?"
What a wabbit hole this is turning out to be, 321 posters/abstracts for CLL, adding BTK pares it down to just 105, +relapse 17, or +R/R 29.
BTKi taken to progression will affect the next line of therapy. Not enough in the abstract to see if short duration use of BTKi in V+I, A-V-O, BVO or an early switch due to intolerance has an effect. This also found V+O was better for R/R than VenR. Prior CIT before BTKi also reduced time to median PFS.
"Patients with BTKi-exposed CLL, particularly those with prior disease progression on BTKi, had worse outcomes. Our study identified CK as one of the most important baseline predictors of adverse TFS and OS in the overall cohort of patients, supporting karyotype assessment for prognostication prior to Venetoclax treatment."
Short duration (SD) VenR for R/R CLL is repeatable with reported good response to BTKi and Ven mono after progression. MURANO had increased 33% TP53 mutated but 30% mCLL was about the same as TN, so not quite as heavily biased to the "difficult to treat". The patients that were in follow on study for re-treatment were of course even more heavily biased to the poor markers. 61% of those assessed had TP53/p17 aberrations, 4% mCLL and 55% had 3 or more genomic complexity.
Progression free duration is short on non covalent BTKi after relapse on covalent BTKi, This paper on 2nd line pirtobrutinib raises the question whether pirtobrutinib would be better as 1st line. Different BTK mutations appear during pirtobrutinib.
I think 1st line doublet SD Venetoclax combinations and hold of from BTKi monotherapy until later after repeated SD Venetoclax combination re-treatments will give a longer total duration than BTKi as 1st line. But those repeated SDs come with the risk of Venetoclax resistance which would prevent it's use at EOL.
I expect AVO and/or BVO SDs to become the gold standard in CLL 1st line treatment very shortly. This will make it imperative that Obinutuzumab is administered and not given up on due to IRR. It can require quite heroic measures to de-sensitise patients and get the first 100mg dose into them.
Your post reminds me why I should take a holiday from health unlocked, I asked quite a simple question more directed to those who had experience of reLooking at their ibrutinib schedule. Whatever you’re saying is completely beyond me and doesn’t seem relevant to my question
Point taken, but I did point out in my initial reply to you that "You are approaching the median time for when people become resistant to a BTKi and going to alternate days of a reduced dose of ibrutinib might just hasten that happening - we really don't know." johnliston asked for more information on that for first (front line) and relapsed/refractory progression free survival and I asked Skyshark if he could provide that info. His first paragraph is reasonably relevant to your situation, bearing in mind that results on ibrutinib aren't as good, because people find that they can't tolerate the side effects - just as you have experienced
I have gradually lowered my dose of Ibrutinib and take 120 mg a day. Im in the uk and when I asked about a holiday I was told I would lose the funding if I stopped. My dose was then lowered around a year ago. The consultant is happy with my numbers and I am in remission. I need ivig every 4 weeks. I get joint pain and lowering the dose has helped but not stopped it. It is less often and much better than before. Anne uk
Thank you so much Anne for your reply, it is good to hear of your experience. Oh that joint pain can be a real dampener on joy!!! I’ll add you to my information gathering. And we could keep each other posted. Thanking you
I am surprised every time I am told my numbers are good. They would like my platelets to be higher. 126 at the moment. I was diagnosed in 2001 and had chemo in 2010. I have also been taking Ibrutinib for 4 years. It was relatively new in the uk and now they accept it causes joint pain. Like you it worked really quickly. Straight away I had my hands curl up with joint pain. I had painful knees and couldnt drive. As the dose was lowered there was an improvement. My hands and wrists now and again. Its hard to know if other pain is the Ibrutinib but I can cope.
I have stopped for a few days to have treatment. It hasnt affected my numbers but the pain started again and it was worse when I took them again.
I worry that the low dose might not be enough and unless the pain flares up I will carry on and hope it keeps working. Anne uk
Bit extreme, move to Liverpool! Or anywhere that's willing to follow the Clatterbridge Algorithm.
All paths have Acalabrutinib on them as 2nd line. Zanubrutinib is also approved for 2nd line for everyone. Both of these 2nd generation BTKi drugs have fewer reactions than 1st generation Ibrutinib. You would have to progress to a treatable stage before re-starting treatment.
Hi Wendy,I had also joint pains with ibrutinib, so my specialist change it in acalabrutinib (CALQUENCE). The joint pains are really reduced to a minimum.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
When that treatment choice is lacking, the testing usually doesn't get done either. The challenge with ending BTKi maintenance therapy is that even after 4 years, if you have the wrong prognostic factors, as soon as your CLL is no longer inhibited by the BTKi, it's possible to have tumor flare, when CLL comes back with a vengeance - so much so that it takes biopsy assessment by CLL specialists familiar with Richter's Transformation (RT) to determine whether or not the tumour flare is RT.
We are all one big experiment for the drug companies
Confused are the dr.s still using chemo with new drugs
New to CLL and worried about upcoming holiday.
Cardiac side effects from drugs: Predictable?
Update of Marty’s Idelasilib “Holiday.
