Just wondering, seeing as Zanubrutunib is now FDA approved in the USA, if one were to be starting a BTKi drug, having never been on one before, would there be any reason to choose Acala over Zanu?
My only rationale would be this (& I assume I'm wrong about it):
maybe starting with Acala could be useful in that, if side effects proved too bothersome, one could then switch to Zanu, whereas if one were to start with Zanu, and if side effects again proved too bothersome, there would be no other BTKi worth moving to? Or would moving "backward" to Acala be an option?
In short, all things being equal, would a BTKi-naive patient have any reason to choose Ibru or Acala over Zanu?
--Dave!
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Hi, in several large phase 3 clinical trials Zanubrutinib had less off target side effects than either Acalabrutinib or Ibrutinib.
In the ALPINE trial for relapsed/refractory CLL where Zanubrutinib went head to head with Ibrutinib the results were clear - progression-free survival was significantly longer among patients who received zanubrutinib than among those who received ibrutinib, and zanubrutinib was associated with fewer cardiac adverse events.
In the SEQUIOA trial where Zanubrutinib was compared to Bendamustine plus Rituximab in less fit patients having their first treatment. Zanubrutinib significantly improved progression-free survival versus bendamustine–rituximab, with an acceptable safety profile consistent with previous studies.
Although Zanubrutinib has not been compared directly (head to head) with Acalabrutinib there is no reason to think that Zanubrutinib would perform less effectively than Acalabrutinib. The same applies to 'fit' patients as a first line treatment - there is no data but no reason to think that Zanubrutinib would perform worse.
Patients that are intolerant of either Ibrutinib or Acalabrutinib because of side effects have been reported to be tolerant of Zanubrutinib and able to continue treatment with a BTKi, leading to control of disease and remissions. Because Zanubrutinib causes less cardiac issues than Ibrutinib and they also appear to be less than with Acalabrutinb (from the limited reports) then Zanubrutinib should also be more cost effective as those long term side effects will arise and require treatment.
A better tolerability profile should lead to better compliance and improved disease control and potentially, a delayed need for subsequent treatments. Overall this should provide a better quality of life for patients
In a recent survey (courtesy of CLL Canada) reports from patients who have experience of Zanubrutinib are overwhelmingly positive with 100% of patients reported either a good or excellent experience of Zanubrutinib and reporting that their health and general wellbeing had improved. Most of these patients had accessed Zanubrutinib via a compassionate access scheme or in a clinical trial and patients were predominantly from UK, USA, Canada.
40% of patients reported no side effects at all, 40% reported bruising or petechia which may appear as a rash (which improved over time), the remaining 20% were an unspecified nature. There were no patient reports of hypertension, diarrhoea, nausea, headaches, joint pains or infections – all of which are more common with Ibrutinib and Acalabrutinib. They could also take a PPI
Patients appreciated that the treatment is a tablet that is taken at home, albeit twice a day, therefore reducing their need for hospital attendance. Less side effects mean that patients are much more likely to comply with the treatment and this should lead to improved response and longer remissions.
Wow, Jackie--now that's an authoritative post! Thanks so much!
One question, though; here, lemme quote you:
"Patients that are intolerant of either Ibrutinib or Acalabrutinib because of side effects have been reported to be tolerant of Zanubrutinib and able to continue treatment with a BTKi, leading to control of disease and remissions."
Does this possibly suggest that if one were to start on Acala, maybe ride it a few years, then become intolerant (not resistant, just intolerant), they could then "start over" by moving to Zanu, meaning the Acala years were, like, bonus years on a BTKi? Or don't things work that way?
Also, if I'm wrong, doesn't the great news in your post mean that, for future patients, Acala has effectively been put out to pasture? That there's really no reason to choose it now?
No, it doesn't quite work that way It means that if the arthralgia or increase in your BP was a worry then you could change to Zanubrutinib and not have those side effects.
I would think that how long you respond to a BTKi would be similar whichever one it is. The benefit of Zanubrutinib and the theoretical reason why the responses are so much better is because it's tolerated so well that patients are more compliant, have less dose reductions or pauses and that consistency of dosing means a better, more durable response. The additional benefit is that patients and the healthcare system may not have to deal with serious cardiac side effects in the future.
I have just finished a submission for a UK NICE technical appraisal for Zanubrutinib for both relapsed and treatment naive patients so I had all the information to hand!
It is expected that Pitrobrutinib will be approved for use soon. This is a non-covalent BTK CLL medication that has fewer side effects than covalent BTKs. You could start on Zanubrutinib and then you would have Pitrobrutinib to change to if needed.
Yeah! As I lay awake at night, charting my future in treatments (I've got it all worked out lol), Pirto is currently my final stop, barring new drugs in the pipeline, which I assume are forthcoming, thankfully.
The acalabrutinib headaches are not nice for the first few weeks/months. Also the heart effects which caused me to discontinue it, occurred for me within the first five weeks. Zanubrutinib seems like the best choice first-line BTKi for now, until pirtobrutinib or some other reversible, non-covalent one becomes FDA approved.
I have taken both Acalabrutinib and Zanubrutinib. Zanubrutinib has more off target inhibitions than Acalabrutinib. According to my doctor, side effects are comparable but the profile is a bit different for each. This was also my experience. The Zanubrutinib gave me more numerous side effects than Acalabrutinib. Acalabrutinib was harder on the GI tract but Zanubrutinib came with much more bruising and some skin issues that I never experienced on Acalabrutinib. The joint and muscle pains were similar. The Zanubrutinib was significantly more effective for me and surprisingly I had a nice jump in neutrophils, RBC and hemoglobin within a week of switching.
Years ago I met the father of the woman who developed Acala. He told me there were very few/no side effects. I guess he was trying to allay my fears. I'm not at the point where I need treatment yet, but these posts are a great education. Thank you to all.
I don't think that Zanubrutinib is on the Medicare or Veterans Administration formularies for CLL yet, but it is for other conditions. I'm just not sure that FDA approval alone updates the formularies.
I'm not clear on the Off-Label Medicare use restrictions, even after reading this:
A review of evidence supporting NCCN category 2B off-label recommendations for determination of Medicare reimbursement eligibility.
I imagine the VA has a similar policy, but I found only really old or really specific condition stuff when I searched on "Veterans Administration" and "off-label".
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