Hello everyone. Had some questions about calquence and venetoclax. Reading through each of their official pages about side effects. The side effects are scary for both. But they don't give percentages of risks. And some other medical sites give different side effects that is not on their pages. Calquence apparently can increase risk of new cancers. And venetoclax increases risk for severe infection (my Mother is being treated now for urinary infection that went to her kidney and then blood). She took calquence initially from 3 years up until October 2023, because I rushed her to emergency for extremely high heart rate and blood pressure (she's been on blood pressure medicine for 12 years). They diagnosed her with artrial fibrillation. Her hematologist stopped it because, although not 100% sure, he said it has caused afib in patients (after actually calling the makers themselves). She was then placed on venetoclax and since then. With calquence, she never had any ill effects, until the afib. And her blood work was absolutely perfect across the board. With venetoclax, she always felt weak and nauseous after taking the 3rd/4th pill. Which would last for several minutes afterwards. Her venetoclax was stopped since last Tuesday, when she was rushed to hospital for infection (I even asked a question here regarding this). I'm thinking of switching her back on calquence instead of reducing her venetoclax to 2 pills instead of the 4 (as her doctor suggested). But after thoroughly reading the side effects of possibly increasing risks of secondary cancers, I'm scared. Scared of both medicines now. Basically stuck between a rock and a hard place (secondary cancers vs severe life-threatening infections). Any help/knowledge/insight from anyone on their or others experience, they know of, who developed new cancers on calquence? Infections on venetoclax? Risk percentages? Bless you all.
Long, but much needed post about calquence vs ... - CLL Support
Long, but much needed post about calquence vs venetoclax
Hello Lee, I am currently on calquence. I tried to add venetoclax to get a remission, but I couldnt tolerate venetoclax due to stomach issues.
I do not know your source for calquence causing secondary cancers, but be aware such statistics can be misleading. I did read where folks taking calquence had a 12% chance of secondary cancers, mostly skin cancers. But I could not tell if that warning took into account that all of us with cll, treatment or not, are at increased risks for secondary cancers. I have read that is up to 17% .
So Im not sure without reading your source if the risk posed by calquence is above and beyond the risk we have anyway as a result of having Cll. Or is the calquence an enhanced risk?
One reason doctors prescribe new drugs like calquence and venetoclax, to my understanding, is because they carry less risk of secondary cancer than chemo like FCR.
There is no real decision for me, I can’t tolerate venetoclax. Left untreated, my cll would likely kill me, so calquence it is.
I might also observe that skin cancers seem to be the biggest risk as secondary cancers for cll. Skin cancers are often very treatable, when caught early. I screen with a dermatologist at least once a year. I also do my colonoscopies as recommended and do regular prostate screenings. If you go the calquence route, perhaps you can discuss with your mom’s doctor what screenings she can do to lessen her risk of secondary cancer. Thats a good idea for everyone, on calquence or not. We are all at an increased risk for secondary cancers due to our cll.
That fact is not as scary as it seems. The vast majority of us will not get secondary cancers. All cancers are not created equal. Skin cancers in particular can be very treatable if caught early. Good luck.
Jeff, as always - you are sincerely appreciated! Thanks again!
Since I started, I'll ask for your knowledge on calquence some more. Doctor initially told me that on calquence, people are on it indefinitely. But some months ago, the doctor switched to "it only works for like 4 to 7 years and then you have to try something else". He even denied telling me that she could use it for many years as long as it keeps cll at bay.
Lee, I think that “being on calquence indefinitely” and it may “work for 7 years or so” are not really such contradictory statements. Nor is saying “she could use it for many years as long as it keeps her cll at bay”.
Calquence is a very new drug and I dont think there is clarity yet as to how long it works. We do know that some folks who started on a btk drug as a first treatment are still doing well ten years or more out, although many dont make it that far. A conclusion one might draw from that is that for people starting calquence in their 70s, it indeed might be the only cll drug they will ever need. People who take a btk drug as a second or third treatment are more likely to become resistant in a shorter time frame. Those with 17P/TP53 cll might also, on average, have shorter remissions.
These are just averages. Your mother might be one who can take calquence ten years or more. And they are having success with second generation non covalent btk drugs that can overcome resistance. We can maybe tack on a couple years with the new btk. Then we have venetoclax and its newer generation drugs with hopefully less side effects.
It’s easy to see how your mom and I (I know how old she is) can cobble together Cll treatments to take us out to near, or past, our normal lifespans. And thats just with existing drugs, not with the many, many cll drugs in development. Ibrutinib and Calquence didn’t even exist for many folks on here at their diagnosis, just as us later diagnosed folks will see new drugs.
I’m sorry for the miscommunication with your doc, perhaps he could explain things better. Some of the misunderstanding does seem semantical to me as I do consider myself as of now taking calquence indefinitely, but I am acutely aware indefinitely could only be 5, 7, 10 years or more until it stops working . Good luck to your mom, it’s good you are so proactive in her care.
My wife is on Calquence and it has been available for about 4 years in the USA, so I do not understand how it can be known that it only works for 7 years.
Calquence has been in trials for a bit longer than that. I suspect that most cll experts expect that, in terms of efficacy and progression free survival, that calquence will mirror ibrutinib results in those categories to some extent. Since both drugs use an almost identical method of action, it’s reasonable to think that certain mutations in our cll will lead to resistance to both drugs for some people around the same time. Although to your point, Zanubrutinib is said to be outperforming ibrutinib in progression free survival.
I ask my doctor on almost every trip to MD Anderson how long do they think I can take calquence and not progress. I think they probably know more than they let on, but the stock answer I get is always “we dont know, but we do have a number of patients ten years and more out from starting ibrutinib who still have not progressed”.
Thats actually good enough for me to keep me from ruining my days worrying - There’s evidence to hope I never become resistant, if i do I still have options, and me worrying about it ain’t changing a dang thing anyway. (Oxford comma)
The 7 year median use for any covalent BTKi must be based on the experience with ibrutinib - and even that's likely to be understated for those with good markers, particularly if ibrutinib was their first line treatment*. I stress median, because there are early ibrutinib clinical trial patients that have managed to last over a decade on ibrutinib - and most of those had had prior treatments with FCR, BR and other 'chemo' treatments.
* The older chemo treatments worked in part by deliberately causing DNA copy damage during CLL division, triggering attempted repair (if the CLL isn't TP53 mutated or 17p del). Apoptosis is then triggered if P53 hasn't been able to repair the DNA. The problem is that this repair can cause the BTK mutation that makes BTKi drugs ineffective. With the slow operation of BTKi treatments, eventually any BTKi resistant sub-clones remaining after prior treatment, become dominant and the CLL gradually returns.
Neil
Thats a great explanation, Neil. A lot of that was news to me and provided very interesting information. Thanks for the info
🥲 I wish it was the magic pill. It’s scary to think I can run out of treatment options.
Thanks Jeff. I almost forgot about artrial fibrillation. The doctors aren't 100% sure it caused it (obviously, they can't be) but going off of side effects listed that others have experienced, they switched her to venetoclax. The other question I forgot, would it exacerbate her afib symptoms if she went back to calquence, or once afib occurs, it can't be further detrimental? I won't be seeing her doctor until the end of the month, and he is hard to reach, so anything you might know about that (afib).
How does your mother feel about the choices? It may take awhile to ferret this out with her ( I wouldn't do it in the office) in a relaxed conversational manner.
She's from overseas, so her understanding of English is kind of limited. But she did get upset about the change because she felt fine on calquence and doctors said she's was doing amazing in it. Her blood counts were all perfect. But they stopped it because of the artrial fibrillation. Which the doctors aren't 100% sure it caused it, only going by it happening to others.
Ah, understood. Well... as much as any outsider can.
My mother is 88 so we've had many conversations about what aging inevitably leads to, so if she were hypothetically in this position she's not the one to prolong lingering.
She'd take her chances and go with what seemed to be working the best for her short term.
Six of one or half a dozen.
Sorry for your stress.
Thank you very much !
I have been on both Calquence and now on Venetoclax. I am on a reduced dose of 200mg and haven’t experienced any intestinal issues or infections even though my IgG levels are very low. Interestingly enough I feel much better on Venetoclax than Calquence. Secondary cancers are always a possibility but the risks in my opinion at least outweigh the consequences of not treating the CLL.
Lee, with respect to the "side effects of possibly increasing risks of secondary cancers", targeted therapies such as BTKi drugs (e.g. Calquence/acalabrutinib) and BCL-2 drugs (e.g. venetoclax/venclexta) don't affect CLL DNA, so there isn't a direct mechanism by which they can cause primary secondary cancers, unlike the older chemo treatments. They could plausibly increase the risk if they reduced our T cell surveillance for incipient cancers, however. That risk needs to be compared with what would happen if we don't have treatment, also bearing in mind that our immune system does recover after the CLL tumour burden has been lifted.
We have had several posts on this primary secondary cancer risk and my understanding of the current findings are that targeted therapies don't cause them; they are likely to happen irrespective of treatment, simply because of the way CLL compromises our immune system. T cells work by recognising internal changes in our body cells that are expressed on the cells surface. CLL unfortunately drives our T cells to exhaustion, compromising their ability to detect and destroy any of our body cells that are not functioning as they should.
See for example:
healthunlocked.com/cllsuppo... posted by gardening-girl
and
healthunlocked.com/cllsuppo... by bennevisplace
Neil
Thanks Neil! Another question I replied to Jeff, thought I'd also ask you as you're both knowledgeable/helpful — I almost forgot about artrial fibrillation. The doctors aren't 100% sure it caused it (obviously, they can't be) but going off of side effects listed that others have experienced, they switched her to venetoclax. The other question I forgot, would it exacerbate her afib symptoms if she went back to calquence, or once afib occurs, it can't be further detrimental? I won't be seeing her doctor until the end of the month, and he is hard to reach, so anything you might know about that (afib).
There's definitely a higher risk of atrial fibrillation with BTKi drugs, but the risk also increases with age - hence her doctors being uncertain of the cause, Acalabrutinib/Calquence and other, newer BTKi versions are proving significantly better than ibrutinib with respect to atrial fibrillation risk, because they are more selective for B cells.
Your mother really needs to see a cardiologist to assist with managing her atrial fibrillation. Surgical ablation to change the heart muscle contractions can be successful in severe enough cases, otherwise it's a matter of her haematology and cardiology specialists jointly managing her choice in medications to minimise her overall risk. It's a pity that like Cajunjeff, she can tolerate venetoclax, because that could bring her CLL down to a low enough level (uMRD) so that she could have a CLL drug holiday. That would also probably help with gaining a better understanding of how to manage her atrial fibrillation.
Neil
Thanks again Neil. What is CLL drug holiday, by the way?
A drug holiday is a long break from the use of CLL treatment drugs - many months to years. Basically, if you get rid of as much CLL as you can - and reach undetectable Measurable Residual Disease (uMRD), then provided the CLL isn't aggressive, it can take many years before the CLL tumour grows large enough to again warrant treatment. Unfortunately curing CLL isn't yet possible, with the limited exception of bone marrow transplants and FCR treatment of IGHV mutated folk, which can sometimes cure it.
Neil
Neil, things keep popping in my mind, and I forget some things - last question : Can cll become resistant by switching medicines (calquence, then venetoclax, then back to calquence). Or, taking breaks from them (as my Mom was told to stop for weeks)? An bad effects/wrong turns from these actions?
There are actually cases where previous resistance to one drug disappeared after another drug was used, so the first drug could again be reused. It depends on the sub-clone population present when treatment time again comes round. The last used drug will select for sub-clones resistant to that drug, but they may not have resistance to the previously used drug. More research is needed - we've only been mixing/combining targeted therapies for the last 6 years or so, but it seems to hold that the longer you can go between needing treatment, the more likely that your past treatment can be repeated.
Neil
I think Drug holiday means remission.
I have had Basal skin cancer 3 x in my life. My sisters who are twins have also had Basal skin cancer and they do not have CLL. I think we are more vulnerable to skin cancer going through treatment and as we age. (All the times as kids that we had sunburns.)In the beginning of my treatment the first pharmacist advised me to cover up in the sun due to the CLL and treatment. I am fair skinned so I wear a hat, long sleeves, and comfortable pants while in the sun. We may have a higher percentage for a secondary cancer due to having a compromised immune system. I would follow the CLL specialist recommendation. Take care!👩🦳
Side Effects of Long Term use of acyclovir when on Ibrutinib+venetoclax 
O+V treatment in Canada after Calquence
I am officially off of Ibrutinib
Stopping and Restarting Calquence
