One BR treatment in March 2019.Adverse reaction hospitalised for 50 days renal failure. But recovered numbers gradually increasing doubling over past 6 months. AlC from 3 to 12. Meeting last week with specialist who is considering Ibrutinib. I questioned as to why not Acalabrutinib as i understand both are available in Australia on the PBS. He appeared not to be aware of Acalabrutinib on the PBS. I then adked should i have a new Fish test. HE said why would you want to put yourself through this again. Last test done in 2016 at dx. Should i insist ?
My questions are Ibrutinib or Acalabrutinib? And which treatment is kinder to the kidneys. Efgr 40 -45.
Should i have a new Fish test.
Regards to all
Joffre
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Joffre1
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Joffre, I think there is a growing sentiment among Cll doctors that acalabrutinib is a better choice for starting out for most than ibrutinib because the drugs have similar efficacy, but acalabrutinib has less serious side effects. There is some study out there that would suggest Ibrutinib does a better job at restoring our immune systems, but that isn’t clear yet. I switched to acalabrutinib and am having less side effects with it.
I would think it is standard practice to repeat FISH testing before treating. It’s a blood test, so I am not sure what your doctor means by saying he doesn’t wish to put you through it, it’s just a matter of ordering the test from your next lab work. Perhaps the means he doesn’t want to put you through any worrying your FISH results have worsened and you have new mutations.
Repeat FISH testing is done to inform treatment choices. Since your doctor probably plans to put you on ibrutinib no matter the FISH results, he thinks the test is not needed. I would argue that knowing how your FISH test has evolved over the years might help inform other treatment choices. I am not an expert, but from what I have read, most CLL doctors in developed countries would repeat FISH before a new treatment.
Below is a link to an article discussing the importance of repeating FISH testing before a new treatment choice.
Your questions are excellent, and you seem to be more current with modern CLL practices than your hematologist. This is exactly why we suggest getting a 2nd opinion from a CLL expert before treatment. I don't know if that is an option for you under your PBS.
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Although I have no medical training, and would defer to an experienced CLL expert doctor in Australia, I would expect that you would be told that it may be many months until your CLL progresses enough to meet the guidelines for treatment, and that doubling time is not relevant until your ALC is over 30k. Please see this pinned post:
The reason to repeat a FISH test just before starting treatment is because the more aggressive mutations can become significant over time, especially after the BR treatment like you had in 2019.
However that information rarely affects the treatment choices these days.
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For the question of Ibrutinib vs. Acalabrutinib, I would expect that you would be told that there is more experience using Ibrutinib, and only a few patients develop side effects that require shifting to the newer Acalabrutinib. A CLL expert should be able to explain whether the larger once per day dose of Ibrutinib or the smaller twice per day dose of Acalabrutinib would have more or less impact on the kidneys.
A relevant excerpt from a recent Clinicial Care Options Answers to FAQs on State-of-the-Art Management of CLL
Guidelines recommend both acalabrutinib and ibrutinib as options for CLL treatment. What factors do you consider when choosing between these 2 options?
Jeremy S. Abramson, MD, MMSc:
For the average patient, we choose based on efficacy and safety, first and foremost. The ELEVATE-RR data in the relapsed/refractory setting are quite interesting. Compared with ibrutinib, acalabrutinib appears to be associated with less toxicity overall—including events such as any‑grade atrial fibrillation and bleeding, but also arthralgias and myalgias, which can be really troublesome for patients. In general, I prefer acalabrutinib over ibrutinib in most cases, with a few caveats.
First, if a patient is on a proton pump inhibitor such as omeprazole, that has a drug–drug interaction with acalabrutinib. If the patient cannot stop the medication or switch to an H2 blocker, then I would prefer ibrutinib. Second, if a patient is experiencing intolerance to acalabrutinib, then they can switch to ibrutinib. Third, I would consider ibrutinib in patients with del(17p) because we have the longest follow-up data showing long‑term durability of remission with ibrutinib in this population; we currently lack long-term data for acalabrutinib among these patients. Finally, I prefer ibrutinib when I see those rare cases of CLL with central nervous system (CNS) disease. We have much better evidence for CNS penetration with ibrutinib and a little more data on ibrutinib activity in CNS lymphoproliferative disorders.
Anthony Mato, MD, MSCE:
I think both BTK inhibitors remain reasonable options because both have great efficacy data. There is less cardiovascular toxicity with acalabrutinib, which is a major factor. But differences in discontinuation and toxicity rates have not yet translated into an observable difference in efficacy, so both are great options. As I mentioned earlier, selection really depends on how each agent has been studied—the patient populations, combinations, and so forth.
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