Zanubrutnib

[Fwanni]

Has anyone been on Zanubrutnib, post Ibrutnib? Or know of it? It is apparently a new front line 'trial'?

[lankisterguy Volunteer]

Hi Fwanni,

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It's well beyond a "trial":

fda.gov/drugs/resources-inf...

FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma. On January 19, 2023, the Food and Drug Administration (FDA) approved zanubrutinib (Brukinsa, BeiGene USA, Inc.) for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).Jan 19, 2023

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And: nejm.org/doi/full/10.1056/N...

zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.....

The percentage of patients with an overall response was higher in the zanubrutinib group than in the ibrutinib group. The safety profile of zanubrutinib was better than that of ibrutinib, with fewer adverse events leading to treatment discontinuation and fewer cardiac events, including fewer cardiac events leading to treatment discontinuation or death.

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We have had 229 previous posting discussing zanubrutinib (notice that it and Ibrutinib are misspelled in both of your postings- so perhaps that is why you are not getting many responses ).

healthunlocked.com/cllsuppo...

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Len

[Fwanni in reply to lankisterguy]

With thanks. F

[AussieNeil Partner Administrator]

We do have members taking zanubrutinib, but perhaps they aren't prepared to reply to an unlocked post.healthunlocked.com/cllsuppo...

Note that because zanubrutinib and ibrutinib are both covalently bonding BTKi drugs, zanubrutinib will only be a useful for those that can't tolerate ibrutinib, not those with CLL which has become resistant to it. Non-covalent bonding BTKi drugs like pirtobrutinib should usually work in this case, but it's only available via clinical trials.

Neil

[Rrriver in reply to AussieNeil]

Hi Neil, My understanding is that Ibrutinib is the first front line BTK with acalabrutinib and zanubrutinib second line BTK’s. Zanubrutinib and acalabrutinib are very close , but zanubrutinib because of it’s Pharmacokinetic properties stays in your bloodstream for the entire dosing time and is more btk specific. Acalabrutinib is more tolerable for elderly ( over 80 ) patients that find too many side effects with Ibrutinib. I like the idea that zanubtutinib in in your bloodstream all the time to handle btk’s as they present themselves rather then waiting for your next dose. My oncologist says she will put me on zanubrutinib if I can’t tolerate acala for some reason.I am so happy we have all these new treatments , because when I was diagnosed with cll in 2014 we only had chemo.

[AussieNeil Partner Administrator in reply to Rrriver]

That's a pretty good summary! Acalabrutinib presents as a cleaner drug than zanubrutinib (see attachment), but with the available capsule/tablet strengths, it's easier to reduce the dose of zanubrutinib.

Off-target effects of CLL BTK drugs vary. Second gen. versions are cleaner than ibrutinib.

[johnliston]

I do know of one person who is now taking Zanubrutinib after becoming resistant to Ibrutinib. This person was on Venetoclax in between and became resistant to that also. Lymph nodes went down right away, it took time for the WBC to come down and it's not back to normal yet. Other blood counts are starting to recover. I believe it's been about 6 months on Zanubrutinib. I see this person about once a month and always ask if it's still working. There have been other reports of this happening.

john

[AussieNeil Partner Administrator in reply to johnliston]

When you see them next, please ask if they switched to zanubrutinib due to ibrutinib failing to keep their CLL under control (resistance developing) or the side effects becoming too much to tolerate (intolerance). The former would be most unlikely from a pharmacology science perspective).

You could save this post via the "Save post" button under the post and reply to it when you see them next.

Thanks,

Neil

[johnliston in reply to AussieNeil]

Neil, I know it was because of resistance developing after 5 years on ibrutinib, Venetclax was given at that point as a solo treatment, it lasted 2 to 3 years. Then they were waiting for Pirtobrutinib approval and decided to try Zanubrutinib in the mean time. I know it's very strange.

john

[AussieNeil Partner Administrator in reply to johnliston]

Actually, what you describe is not at all strange, now that we know that venetoclax was used. There have been cases of BTKi resistance disapearing after venetoclax treatment. Presumably the CLL sub-clone with ibrutinib resistance is very susceptible to venetoclax in these cases. With venetoclax vanquishing that clone, maintenance treatment with any covalent bonding BTKi will again effectively control the CLL until a resistant sub-clone again develops.

[johnliston in reply to AussieNeil]

"rare" probably would have been a better word than "strange"

john

[scryer99]

Am in month 5 of it, as part of a clinical trial, and not post-ibrutinib - I was treatment-naive going into trial, more in my profile. Zanubrutinib was pre-FDA-approval when I first received it but has since been approved.

It has had a positive effect, and side effects have been non-zero but manageable. It knocked my ALC back about 50%. I did not feel 100% until later in treatment when they added a second drug. I had some petechiae, fatigue, and joint pain, and I can note some difference in those side effects in the first two hours when taking the drug.

On the whole it has been a manageable drug with positive effects. I would not expect it to push your CLL to remission, but as a management regimen, it's a solid option.

[Caringagain42 in reply to scryer99]

what other drug did they add?

[scryer99 in reply to Caringagain42]

A new study drug in the BCL2 family. It's been fairly effective so far but I have several months to go before completing the trial.

[Caringagain42 in reply to scryer99]

interesting. Good luck with this trial. Thanks for responding.

[labgypsy in reply to scryer99]

I was on Ibrutinib for three months. I developed Atrial Fibrillation. I requested Zanubrutinib and have had no further heart issues. I have now been on Zanubrutinib for 5 months. My white count is at 23,000, down from 247,000. Fatigue and joint pain have improved. Petechiae come and go. My neutrophils are increasing for the first time in 6 years, giving me something to help fight infections.

[flipperj in reply to labgypsy]

Zanubrutinib also helped my neutrophils significantly.

[bachplayer13]

ive been on zanubruatnib since 2021 before it was approved for cll. i could not tolerate side efffects of ibrutunib and its a long story but despite not being resistant to acalabrutunib it stopped working for me and i had disease progression. in my case it was a drug drug interactions that made the zanubrutunib not work and it was a drug i had to have. so we switched to zanu and its been great. yes easy bruising and bleeding but otherwise zero side effects. well i am pretty anemic also but i can live with it. there have been papers out and its supposed to be the best new treatment oujt there in the btk class. patients can accctually stay on it due to lack of side effects. i'm happy to have it

[1935husband]

I switched to Zanabrutinib 2 months ago.

Blood work now near normal and fewer side effects although they were very little anyway after a rough start on Ibrutinib

[Mogal]

hi Fwanni,

I am very pleased with Zanubrutinib and its lack of bothersome side effects. I have been on it for well over a year and a half now and it seems to be working well, as my labs are normal. Previously had been on Ibrutinib, but it caused cardiac arrhythmias, was switched to Acalabrutinib , but after 4 months of unrelenting migraines, I got the OK from my hematologist to switch to Zanubrutinib . Hope it works well for you too.

[flipperj]

I’ve been on Zanubrutinib for over a year. It’s been superior to Acalabrutinib for me and is approved for front line therapy in the US.