Back to the drawing board

[Thundercat2]

Hello dear people

Just returned from a visit with CLL specialist. Finished O+V in February 2023 and latest WBC (33,000) and lymphocyte counts (75%) so rising again. Feeling sad, angry, scared, & frustrated. My specialist first recommended Car-t which really caught me by surprise. That sounds so intense and although the outcomes are improving I just don’t know if I'm ready for that. I had a good experience overall with O+V (1 yr) and got to UMRD in bone marrow, but its steadily returning (I’m 11q unmutated). I failed on Ibrutinib (it was working) but side effects were too much. Specialist said Zanubrutinib is a good option and I could do the O+V again, but thinks I will get a lesser remission on it this time. Still it would be 2 years on Venetoclax and the Ven is a known quantity for me. Wondering if any of you have thoughts/advice. I’m active watch and wait at this time but know I will face this sooner rather than later.

You get to a good place, you’re moving along nicely and then it rears its ugly head. Sorry to be Debbie Downer, it’s just hard. Luckily I’ve been feeling well, my other numbers are good and I don’t want to minimize that. I just have to pick myself up, dust myself off and soldier on. Thanks for listening.

Tcat

[bennevisplace]

I'm sorry that you're faced with another phase of treatment sooner than you'd have liked. From what I've read, 11q del CLL can be that way, but it can often be treated successfully with a BTK inhibitor. You said that for you Ibrutinib (monotherapy?) was effective but not tolerated, so your specialist's suggestion to try Zanubrutinib now makes a lot of sense to me. As a treatment for R/R CLL it has been shown to be more effective than Ibrutinib with fewer side effects nejm.org/doi/full/10.1056/N....

[SofiaDeo Administrator]

I'm somewhat similar to you, not tolerating ibrutinib and getting only 2 years remission (but on V alone, not a doublet).

If you are near to any trial sites, and are interested, there is a study expected to be FDA approved within the next 3 months. It's comparing V&O against V&S(sonrotoclax, a new BCL2 inhibitor) with V&R as a control group. My specialist is checking, he thinks the FDA-approved meds (V,R, O) will be paid for by the study, as well as copays for specialist visits, CT's, etc.

There also are a few BTK degrader drug trials going on. I saw him yesterday, I am definitely out of remission & doubling time 3-4 months once again.

I don't think you're a Debbie Downer, it's upsetting to find out the CLL is rearing its head again. It would be nice to get the 5+ year remission a number of people get, but at least we can do a repeat, the treatment didn't totally fail. I try to think "more positive" like that, or I'd go crazy worrying about it all! I'm sort of resigned to "treat a few years, off a few years, treat a few years." Which is better than "treatment failed" IMO.

[Thundercat2 in reply to SofiaDeo]

Thanks Sofia. Yes we are similar it seems. I did hear about the BT degrader trial and good to know about the Sorontoclax trial. I'll have to look into that.

You're right about the fact that we have options, but try as I might I still get disappointed when it rears up again, although maybe not as severely as before? I do like thinking of it as on and off rather than "treatment failed" I'll be keeping that in mind!

[SofiaDeo Administrator in reply to Thundercat2]

I misspelled "sonrotoclax" as "sorontoclax" haha, I've edited my reply!

[cajunjeff]

Hello thundercat. Sorry to read you are evidently falling out of remission.

I personally like the idea of zanubrutinib or acalabrutinib, both reportedly have less side effects than ibrutinib. There is some evidence that 11q cll patients do well on btk drugs. A btk drug could buy time while other options are being developed. And I would imagine you can still do another round of O+V if you are intolerant of zanu or acalabrutinib, or if resistance develops.

If you like and have confidence in your cll doctor, I would let him make the call. It seems from your post that he favors zanu, but that not clear. If you are not resistant to btk drugs, they might work for who knows how long, and then you could maybe buy another couple years with pirtobrutinib if zanu stopped working.

Early resistance to btk drugs is uncommon, to my understanding. There are some gene mutations associated with btk resistance they can test to see if resistance is likely. I do not think that kind of mutation testing is commonly done with cll, but I do not see the harm in asking your doctor if mutation testing would inform his decision on what therapy he recommends. Just a thought. Good luck. I think an argument could be made to do V+O now and save the btk drugs too.

[Thundercat2]

Thanks so much Jeff. I really appreciate your thoughtful response.

I can't help but wonder about doing the V+O again, since I would then be saving the BTK's for down the road. The doc is conferring with her team and getting back to me so that will be good as well.

No one here so far has mentioned Car-T. I feel like it's too early for me to jump into that although the doc was quite positive about it.

[ArtistBlacksmith]

Hi, We are on parallel tracks- same mutations and we finished 12 months O+V at the same time!! I relapsed last year after a 17 month remission, O+V did not get me a complete remission or to uMRD (close but not quite). I started Zanubrutinib in October last year after a consult with arguably Australia's best CLL specialist Prof Con Tam. He thinks for us 11q Unmutated that Zanu is the way to go. He ran the clinical trials here of Zanu, so I figure he would know. He also thinks there are are a number of other options before CAR-T. I brought this up as a clinical trial was open at the time and I would have qualified. Sooo initial side affects of Zanu really sucked but 6 months in and it is almost like there is nothing wrong with me. On O+V I was still getting periods of fatigue, much, much less on Zanu. So I'd suggest have a solid conversation with your Dr about Zanu. All the best!

[Dragonfly2007]

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