What is available as treatment after Venetaclex finishes in 11 months for me if I relapse?

[Veebeegeebee]

What is available for me when I finish this course of Venetaclex in 11 months time if I relapse? I’ve had almost 4 years of Ibrutinib prior to this regimen. Just curious as to what is out there?

[AussieNeil Administrator]

This post and the following replies lists pretty well all the CLL targeted therapies, approved and in clinical trials: healthunlocked.com/cllsuppo... Of course, having them approved for use in Australia is a different matter.

I see that you are inquiring on behalf of your husband and it's a bit hard to work out his history without a summary in your (his) bio, (you can update it here: https:/healthunlocked.com/profile/edit ), plus you might like to post locked for privacy reasons: healthunlocked.com/cllsuppo...

Without spending my time trying to find out why your husband stopped ibrutinib, I gather he couldn't tolerate it, rather than his CLL becoming resistant to it? In which case he could do well on a second generation BTKi treatment as these are also considerably better tolerated than ibrutinib. If his remission lasts for more than 2 years - the longer the better, again, provided he doesn't develop resistance to venetoclax, I expect that can also be repeated until remission times aren't acceptable or resistance develops. If he exhausts BTKi and BCL-2 treatments, then it comes down to what's available via clinical trials or what's been approved in the meantime. Per my YABTKi post, ibrutinib is a first generation covalent bonding BTKi drug. When resistance develops to ibrutinib, acalabrutinib and zanubrutinib and any other approved covalent bonding BTKi drug, it's possible to switch to non-covalent bonding BTKi drugs, which also look to be better tolerated than ibrutininb.(None have been approved yet by the FDA, but the approval of pirtobrutinib looks close. (It was approved for Mantle Cell Lymphoma at the end of January 2023, so people in the US can have it prescribed off label for their CLL.) After those avenues are exhausted, we fall back on clinical trials like CAR-T, which is available in Melbourne.

Neil

[Veebeegeebee in reply to AussieNeil]

Ibrutinib stopped working after nearly 4 years use. If I knew how how to access my previous posts Re George’s journey I would & refresh info but I don’t know where to look

[AussieNeil Administrator in reply to Veebeegeebee]

It sounds like you have established two logins with different usernames - that can happen. If you remember your previous username, you should be able to do a password reset. If you can remember your past username and can't do a reset HU Support should be able to assist.

Neil

[Veebeegeebee in reply to AussieNeil]

Hi Aussie Neil, I made comments when George was first starting on Venetaclex in Feb 22. I’ve ‘stumbled’ upon them here today but I’m having a vague moment ATM.

[AussieNeil Administrator in reply to Veebeegeebee]

You've posted and replied about your husband here:

healthunlocked.com/user/Vee...

When you are less vague , perhaps you can copy them into your/his bio here: healthunlocked.com/profile/...

Neil

[Shepherd777]

My wife after about 11 months on Venetoclax took a vacation and remained in clinical remission for about 3 and 1/2 years. They told us Venetoclax would probably work again, but suggested we try Calquence)Acalabrutinib. We were not able to tolerate Imbruvica prior to Venetoclax. We have been on Calquence less than a year and have reached clinical remission again. Not sure when the next vacation is, but Calquence was not as harsh. However, we still would like another vacation at some point.

[Jm954 Administrator]

Most probably the next course of action would be to start Venetoclax again but that might depend on the length of your remission. If it's only short then you may not respond again and you will need to look for a clinical trial of a new drug. What is available to you may depend on your fitness and any other comorbidities.

Jackie

[Veebeegeebee in reply to Jm954]

thank you, we didn’t realise this was an option to start Venetaclex again!

[SofiaDeo in reply to Veebeegeebee]

My understanding is, if one gets at least 2 years remission, a repeat of the same treatment can be considered. I had this discussion with my specialist last December. Of course, if other organs have changed and other health concerns have arisen, it may not be ideal to simply repeat what was done before, but it can be considered.

We have to remember CLL isn't like solid tumors, where there is some "defective cell" that started, and if one can get rid of all the defective/cancerous cells, the cancer is pretty much gone. We have at least one defect in our lymphoid stem cells, such that we produce defective lymphocytes that don't die normally, as well as potentially other defects of the other lymphoid cell lines. Non lymphoid cell lines can also be affected as the bone marrow get crowded with defective lymphocytes; these lymphocytes don't necessarily release into the bloodstream like they are supposed to and this "crowding" in the marrow can affect other stem cells trying to produce other things. Our treatments get rid of these lymphocytes and free up the bone marrow so the other stem cells can do what they normally do. But if the basic defect in the bone marrow hasn't been fixed 100% by the CLL treatment, at some point the defective lymphocytes grow enough to once again become detectable and start affecting other parts of the marrow. This is why a "stem cell transplant" is currently considered a potential cure; you are clearing out all the defective stem cells, trying to re-establish only healthy, normal ones. So our problem isn't just "kill off the bad lymphocytes" we need some sort of marrow repair/reset. If the disease is killed off but takes a number of years to grow back, it's considered reasonable to include a repeat of previous treatment in the options, if the patient wants to consider it.

[Pacificview in reply to SofiaDeo]

Wow, thank you for unpacking that. You just answered a big question I have had.

[skipro]

awe so many good options

V + O

V alone

Pitibtutinib is in phase 3 trials and should be available before you relapse

? ZANU plus O may come available

So enjoy your break from treatment

I had relapse after FCR and am starting V + O tomorrow. Wish me luck

Skipro