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
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Thundercat2
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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....
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.
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!
Maybe it's because I am a Tolkien fan, but "Sor-on" comes more easily to me than "Son-ro". Since it's closest to "Sauron" lol! I like the idea of a "Sauron" drug, fighting off the CLL hobbits & elves.
I like my naturopath’s analogy — it is like running a marathon, and you are in it for the long haul. You need to stop for a drink of water along the way, but then you are right back in the race living your life.
I am in same boat, but I am being checked out for RT again. I suspect that remission is coming to a close as started having milder night sweats after V&O remission of 1.5 years. Please pass along any information on mentioned trial. Maybe time for me to start looking. Blessings.
I will when it becomes available. It isn't even in the Clinical Trials database as "Not yet recruiting" right now. My doc says I will be on the "call ASAP" list, we've discussed my starting treatment before my tumor load gets so high I would need to be hospitalized again, when starting the BCL2 inhibitor part. Plus, I would want to get the bulk of "heavy initial testing" done before winter. With the wild weather swings, the Interstate can get closed. So I hope all the chaos at the Federal level in the US doesn't push things off too much.
There are studies involving sonrotoclax for relapsed patients currently enrolling, if you are interested in this drug & looking for something sooner.
Thanks for catching my typo! I changed it to S&O. The trial is comparing one of the two BCL-2 inhibitors, V or S, along with the newer MAB O, against a control group of V&R.
There is a trial pitting S&Z against V&O that's recruiting:
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.
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.
I think your misgivings about CAR T being your best option at this stage are well founded. Durable remissions in CLL patients have been the exception rather than the rule, versus relative success for targeted drug therapies. This may be why no-one in this community is plumping for CAR T in your case, when there are several more obvious ways forward. We would all, I'm sure, be interested to have an insight into your consultant's thinking.
The main issues with CAR T, apart from the cost, are well known and what applies to CLL applies more so in solid tumours. Huge sums are going into research and technological advances are announced frequently, e.g. ajmc.com/view/new-generatio... so it seems logical to choose a drug-based route that will likely buy you time before you might wish to revisit what should be a technically improved CAR T option x years from now.
Yes, that validates my thinking. Surely being at a research hospital and because it's an open clinical trial right now, they are prone to promoting the trials.
I am a little leery of Car-T but my current CLL Specialist from Germany has done a lot of Car-T. I will see him next month and ask some questions. Blessings.
She mentions complete remissions (CR) lasting greater than 5 years after liso-cel. She suggests the CR rate of 20% in TRANSCEND-CLL-004 might improve with earlier use & fewer prior treatments particularly with BTK debulking prior to CAR-T (ibrutinib used in an arm of this trial) which reduces rates of cytokine release syndrome and neurologic complications.
Well that does shed some new light on my doctors thoughts on Car-T. Although my WBC and lymphocytes are increasing I currently do not have any palpable nodes. I stayed on Ibrutinib only 4 months and did the O+V for a year. Definitely food for thought.
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!
Hello Artist thanks for the good information. Always good to hear from someone traveling the same path. What symptoms did you have with the Zanubrutinib? I did very well on the Venetoclax so that is tempting me despite knowing I may not get a very long remission. It was wonderful to be off everything for awhile too.
Wishing you a long and symptom free ride on the Z train!
Our mutations means we'll get short remissions. The first 3 weeks of Zanu were fine, then severe fatigue, muscle aches, splitting headaches that last for days. These were for a few weeks. Then the all over ( and I mean 100% allover) horribly itchy rash began, that last 3 - 4 months. It was terrible. But got through that and since Feb have been good. ALC goes up for the first few months, then starts coming down.
I'm with the others here, I think Car-T is awesome and I'm optimistic on it as a treatment...but I would tend to be more risk averse and choose a treatment that buys you some more time if possible, be that a degrader or alternative BTK. Why rush when that option will be there later if you need it?
I think most of us on this page, feel exactly the way you do at some point (if not several times). Please keep your head up. As I am currently in O and V treatments, I'm a few years behind you or the initial treatment.
I know in the back of my head, that there's a chance, that this might now work as well or as long as I want it too. I've heard 6 months to 12 years, as a general range for my next treatments if this works. The 12 years sounds great, and the 6 months just sounds like it sucks. The Docs believe if successful that they feel comfortable saying 6-8 yrs.
But like everything else, I'm not holding my breath. When I was diagnosed in 2021, I was told I could go decades without any treatments, only to find that just 4 yrs later, I need treatments. So I do understand your frustration. Please keep your head up and try to find the silver linings, even if they don't feel like they are there.
Is zanubrutinib in the same family as ibrutinib? Had a heart attack while on ibrutinib so ended up on venetoclax and got 6 years remission. Now have to choose between venetoclax again or zanubrutinib. Concerned about heart issues.. thoughts?
All the 'brutinib' drugs are in the class of Bruton's Kinase Inhibitors, BTKis. However, they have varying degrees of off target effects on other kinases in our different body cells. (There's also the confusion caused by the scientific name for the drug, and the product marketing name. Zanubrutinib is marketed as Brukinsa and ibrutinib as Imbruvica.) What's important is that the cardiotoxicity risk of second generation BTKi drugs, such as zanubrutinib and acalabrutinib (Calquence) is roughly half that of ibrutinib.
Taking ibrutinib may not have been why you had a heart attack (cardiac arrest). BTKis increase our risk of developing atrial fibrillation and high blood pressure, but they also reduce clotting efficiency.
The ideal specialist to inform you of the best choice with respect to your heart health, would be a cardio-oncologist. Given venetoclax gave you a 6 year remission, if you can't easily find a cardio-oncologist, repeating venetoclax would appear the better choice. You can expect a shorter remission next treatment (we don't yet know what's typical, as venetoclax hasn't been in use long enough for much long term patient data to accumulate), but the limited treatment duration and subsequent drug holiday are tempting.
Neil
Significant improvement in acalabrutinib and zanubrutinib adverse events vs ibrutinib
Hey Thudercat, I'm sorry to hear your remission is over...we went through O+V at the same time, you were a bit ahead of me, I finished in June 2023. I agree with others, I would probably lean towards trying some of the BTKis. Most doctors follow this pathway. Hope you figure it out soon and that whatever you choose that it works well for you. Sending love. Petra ❤️
Thanks Petra. I know we were on the same course essentially. Hope you are remaining well.
I'm waiting for more info from my specialist. The good news is there are many options making the down side -choosing! Fortunately I have some time to decide. And this group is so helpful.
Thanks, Alison. I'm doing well. I had my 6-monthly check up in March and all numbers are still normal for now. It is upsetting to read about others who went through O+V at the same time and how their CLL is rearing its ugly head again...I had a really vivid dream the other night where I could feel my enlarged spleen again and also some nodes - next to my ears- which I had for years even before I was diagnosed...not a nice dream...yes, definitely good news that there are options to choose from. I'm sure you will do well on your new treatment. You are a trooper, you have been through a lot so you can handle this 💪🏻❤️xx
Thanks Petra. Dreams can feel so real. I guess we never get to completely forget the fact that we have this disease. And it is hard to hear when our friends here are going through something tough, especially as it relates to us. But as someone once told me... Tomorrow is promised to no one. I'm glad we have each other to lean on when things are tough and celebrate our victories too. One foot in front of the other and we will prevail! ❤️
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Slow increase in lymphocyte count in the years after V&O
coming to end of V+O treatment
WBC and Neutrophils count dropped
V + O , TP53 and p13
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