Zanabrutinib

[MovingForward4423]

Happy New year, everyone!

I was treated with Ibrutinib for about 2 years, and taken off after a grade 3 event (SVT Tachycardia). It was decided I would stay off treatment until progression. Although I should get somewhere between one and three years in remission, my consultant has already started to talk about Zanabrutinib rather than Acalabrutinib.

Does anyone have any real-life experience with Zanabrutinib? I have read the various studies and trial results that look very promising. I responded incredibly well to Ibrutinib, with my lymphocytes dropping from almost 200 to 26 in 18 days. Within a few months, my blood count was normal, and my spleen had shrunk back to near normal from being half the size of my stomach.

Just personal experiences please, I have access to reports etc...

Rich

[MovingForward4423]

To add to this, does anyone have any updates in regards to reversible BTK's. They seem to be emerging out of stage 2 trials?

[CycleWonder in reply to MovingForward4423]

By reversible, are you referring to non-covalent BTKs such as Pitrobrutinib? I am on this one as part of a phase 3 trial.

[MovingForward4423 in reply to CycleWonder]

do you have resistance to standard BTK?

[CycleWonder in reply to MovingForward4423]

No. I was treatment naive when I started on Nov 1st of this year.

[MovingForward4423]

CLL right?

[Davidcara]

was on Ibrutinib 20 months, switched to zanubrutinib at healthcare organization’s request; less toxicities and less money. Took zanubrutinib for four months; stopped when I got covid in July and will stay off until labs or symptoms say it is time to restart.

Had little issues with Ibrutinib, hypertension that was controlled with three medications. After switching to zanubrutinib, I only needed two meds to control hypertension.

Felt better on zanubrutinib. Although it is 21 extra weekly pills, which is a bit of a pain. But overall worth it for sure.

[MovingForward4423 in reply to Davidcara]

excellent. Thanks for sharing. Yeah 2 tabs a day is a pain. Small pain but when you have to do that all the time…..happy new year

[Davidcara in reply to MovingForward4423]

well actually it is two tabs twice a day, but yes easy enough compared to the alternative

[KirstenSL]

Hi Rich

I am participating in a clinical trial involving Zanubrutinib mono therapy for an initial period followed by combination with a new generation BCL2 inhibitor.

I have been on Zanubrutinib for just over a year, starting mid November 2021. Zanu by itself reduced my lymphocyte count from 275 to 98 in four months (peaking at 542 after 3 weeks as it cleared my lymph nodes and spleen). The subsequent combination with the novel BCL2 inhibitor knocked my lymphocytes down into normal range within 5 weeks.

I have had excellent experience with Zanu and no major side effects. I would definitely take it over Acala as it is a newer drug, more targeted with fewer "off target" effects.

Good luck.

Kirsten

[Snoopy234 in reply to KirstenSL]

I, too,, was taking ibrutinib for two years : one pill a day. It was very effective and my only side effect was broken nails and painful finger tips’ but these were resolved with biotin. Three months ago I had to switch to zanubrutinib because I got another side effect: an ocular edema. No problems with zanu so far and it is also extremely effective. I take one pill in the morning and another one in the evening, but once you get into the habit, this isn’t a problem. Hope all goes well for you too with your new treatment. (No more issues with nails or fingertips, by the way.)

[DaveCll in reply to Snoopy234]

Did it effect your neutrophil count and did the ocular Endema get better when you changed to Zanu?

Dave

[Snoopy234 in reply to DaveCll]

My ocular edema cleared up completely after stopping ibrutinib and six weeks of treatment with steroid eye drops. Zanubritinib did lower my neutrophil count so I have to be careful not to get infections, but this is the case with most ant-cancer drugs. I've only been on it for two months and am due for another blood test next week, at which time I will know more andlet you know.

[DaveCll in reply to Snoopy234]

thanks for getting back to me. I hope all goes well

[AussieNeil Partner Administrator in reply to KirstenSL]

Hi Kristen,

Like you, I expected zanubrutinib/Brukinsa to have fewer "off target" effects than acalabrutinib/Calquence and most definitely fewer than ibrutinib/Imbruvica. So I was quite surprised to see that acalabrutinib wins out among the three. I guess it helped that a senior member of the ibrutinib design team joined the acalabrutinib design team and was able to use their detailed knowledge of ibrutinib's off target effects to improve on them. I've attached a graphic comparison plot of the off target effects of the three BTKi drugs below. I would say that which of acalabrutinib and zanubrutinib best fits is determined by the individual concerned; they are both excellent drugs.

Neil

Off target effect comparison of three BTKi drugs shows acalabrutinib is superior.

[ivy39]

Hello Rich.

After a 2 1/2 year remission after Venetoclax my onc suggested Zanubrutinib. I have been on Zanubrutinib now since mid-November. I have experienced no side effects but know that unlike Venetoclax my bloods will take months before WBCs and Lymphs decrease to their normal levels.

[MovingForward4423 in reply to ivy39]

how about fatigue? I did notice on Ibrutinib I got tired, and a bit foggy.

[ivy39 in reply to MovingForward4423]

Neither applies to me.

[JerrysGirl3]

I was treatment naive whenI had just started on Zanubrutinib in July. Then I caught Covid in August and went off - just 6 weeks. At the time I was still on it my wbc was up to 118,000 I think. After Covid and Paxlovid I couldn't seem to take Zanubrutinib again. I'm totally off meds since. In two months off meds my wbc went down to 33,000 then to 25,000 and all my labs in the green zone ! My recent labs, however, showed a slight increase in wbc to 29,500. I've started to get sweats but not sure if it's the weather which is really warm for winter or CLL starting up again. My issue with Zanubrutinib was high blood pressure 170/100 and was on two BP meds, and my thyroid nodes from thyroid cancer instead of going down, increased in size where it was terribly uncomfortable. Never got an answer why that happened. They're still swollen. Local oncologist put me on GERD pills. Seemed to help for awhile. Awaiting new labs in two weeks to see if numbers are indeed indicating CLL needing treatment. And seeing Gastro doc for possible endoscopy. Would really like to resolve that issue!!!!

Kerry

[ThreePeas]

I was switched from inrutinib to Zanu because my insurance company’s formulary changed. My numbers have been equally good under both of them. My nails are better now; on the other hand my hair is now curly, which is good or bad depending on which look one prefers. The diarrhea seems worse so we are currently trying a lower dose to see if that side effect improves.

[LFCB]

Had severe side effects with ibrutinib, bradycardia and then diagnosed with congestive heart failure. Treatment for that: beta blocker, off ibrutinib for a month stabilized irregular heartbeat. Started brukinsa, exercise program and aside from awful bout with the flu which I am getting over, I feel the best I have in many years. No side effects worth noting, initial blood work good (due for another). Will be interested to see white blood cell count. Platelets have actually improved since getting off ibrutinib but everyone reacts differently. My oncologist chose brukinsa because it seems to have the fewest cardiac adverse effects.

[Mkhait]

My wife had similar case - 5 years on Ibrutinib , then tachycardia and we switch to Zanabrutinib ( Brukinsa ) . Tachycardia is gone, everything was good on CLL side, but after about 6 months her WBC start rising from normal - about 10 to 17 4 months later.

Not sure if it because Brukinsa is not working or something else. Working with our oncologist for the next step..

[bennevisplace]

Further to Len's post of three weeks ago from the ASH conference healthunlocked.com/cllsuppo... the randomised study of Zanubrutinib v Ibrutinib in relapsed/ refractory CLL has been published in NEJM nejm.org/doi/full/10.1056/N... from which the figure below shows the respective PFS and OS curves.

Fig 2

[bennevisplace]

Also from nejm.org/doi/full/10.1056/N... the figure showing respective side effects.

Fig 3