I have posted a few times in response to others about my treatment. Now in Mth 9 and yesterday my Venetoclax dosage was lowered from 400 to 300. I was a bit surprised. The team felt I was being over medicated and that lots of patients are now complaining about stomach problems which could be one reason to drop (not me tbh - more lack of energy and generally feeling off plus minor infections cropping up despite staying fairly isolated). I have been told this will have no effect on my final MRD status. They are checking my MRD status on this blood draw which I think they do here in the UK for us all at treatment Mth 9 but results will take a couple of weeks. Still to continue for the next month with G-CSF injections once a week to keep neutrophils up but these do make me feel ill. I could have insisted on staying on 400 and I can still ask for a further review next month but do I need to? Too early to say whether I feel better on the lower dose or what better will look like!
Confused? Venetoclax 400 v. 300: I have posted a... - CLL Support
Confused? Venetoclax 400 v. 300
Hello Steffi, I have some amateur thoughts on the dosages of meds we take for our cll and why some doctors might be more willing to experiment than others.
Most all the drugs we take for our cll, including venetoclax, went through a series of clinical trials to get approval. The trials look for how safe the drugs are, how effective they are and what is the optimum dose.
Once approved, the drugs come with a recommended dosage, kind of like the instructions on a bottle of Tylenol to take two every so often.
The recommended dosages are not absolute, such that 400mg of a drug would work and 300mg would not. Its just an average dose than landed upon in their clinical trials which balanced giving us enough of the drug to work with the least risk of side effects.
We all usually start on the recommend dose, but does it make sense, for example, that the dose for a 300 lb man should be the same as one for a 90 lb woman? Should the dose be the same for a healthy 50 yr old vs an unfit 80 year old?
I think some doctors stick to the recommended dose for all because they are less likely to be second guessed if they deviate from the recommended guidelines.
I think some other are more likely to use their training, clinical experience and their instincts to use recommended dosages as a guideline and then deviate from the guidelines where in the doctor’s judgment a different dose is warranted.
It sounds like in your case that your doctor thinks your venetoclax dosage can be reduced and still be just as effective for you with less risk of side effects. I had horrible stomach pain with ventetoclax and had to stop. Your “team”, as you say, is not bound by the average dose on the label, which is good. They are free to use their clinical judgment based on their experience in treating all sorts of different cll patients.
It’s a good question you ask. You may ask members of your team to relate their experience in changing doses and how others similarly situated to you have done with dose reductions. The safest route for your team would be to stick with the dosage on the label, even though they think a reduction is warranted. I personally would rather be treated by doctors who use recommended dosages as guidelines that can be deviated from to tailor treatment to specific individuals based on their experience.
Thanks Cajunjeff. That's a good way of thinking about it. I have wondered why at 5'2" and (a little) overweight - gained during treatment, I would be on the same dose as a much larger man. Sorry I called it my 'team' as maybe that is an odd term. I am at the Marsden so I see a variety of doctors and senior nursing staff at what are now monthly visits. Yesterday saw my consultant haematologist who is great and I do trust him. He suggested the drop as he just felt I wasn't coping as well as I should be and those pesky neutrophils just keep on tanking. My CNS (also brilliant and always so responsive) said other patients have also dropped their dosage and 'done well' but I wanted to check in with you guys. Judging by the replies, the future's bright and I shouldn't be concerned.
My V dose was lowered a month ago to 300 and I am feeling better I have to say. My CLL oncologist lowered it as my neutrophils were a bit low. I see him next week to see what my blood work is at this lower dose. I will say I’m not as tired, the mild low grade nausea has lifted and I’m back to full workouts again. He did say he has patients who are even on 200 mg doses and doing fine. No one size fits all on this - V is a potent drug. My impression is adjustments can be made - does not necessarily impact its effectiveness depending on the individual.
Hi,
I started a clinical trial of Venetoclax monotherapy in April 2018. I had some serious side effects — mostly neutrophils tanking — and my dosage was reduced to 300 mg. In November 2018 I was pronounced as being in clinical remission and my dosage was further reduced to 200 mg. I’m still taking 200 mg and doing remarkably well. My only side effect is mild constipation.
This is a really positive reply and hoping for a similar response to the lower dosage. Only day 2 so hard to say at the moment. Would be good to get an update after your next visit. Thank you for taking the time to share
Sunny
so it sounds like you’re saying that dropping from 400 to 300 led to feeling significantly better.
I’m 15 months into my V + O and would really like to get rid of or minimize my side effects of nausea, fatigue, muscle aches, and pains, intermittent, diarrhea, and nonstop URI since December.
I am tempted to try adult reduction as I have read a paper from the Marano study that indicated those reductions had no impact on progression free survival.
Thank you so much. Can’t wait to hear what you have to say
Ski pro
That's good to know. So you got to remission in 6mths. I am on a fixed 12 month programme. Is V a forever pill for you or until it stops working?
Hello. I have been on 300 of Venetaclax for 4 years. I was hospitalized for each ramp up because I developed tumor lysis syndrome. I was upset that I couldn’t make it to 400, but a hematologist while is was hospitalized said he had people on 200 doing very well.
Hello I was originally on 400 of Venetaclax but had stomach problems. the Dr eventually agreed to try 200 and it works fine. As Sunny says one size does not fit all . I am a 9st woman and always queried that perhaps I did not need the same as a much heavier person.
I went from 400mg to 100mg on Venetoclax and got to uMRD. Unfortunately it only lasted a year.
thx
is it OK for me to ask what your genetic markers are?
And was MRD determined by blood or marrow and what was the number?
Thanks,
skipro
Boy that was a while ago. I’ve was put on V&O subsequently, which failed and I got sick and landed in the hospital. I’m now on Zanubritnib. I believe it was a blood test. But I’ve had so many BMBs and blood tests that I just don’t remember. This is my 6th season of chemo and five different drugs.
Steffi50 -
The choice we face is whether to continue dosage, risking severe infection and possibly shorter remission or PFS. The drug comes with recommendations from the manufacturer regarding when to reduce dosage or pause treatment. Subsequent trials do update those sections. I think the most recent update was in 2022, though I'm not sure what changed, because the prescribing info covers more than CLL.
accessdata.fda.gov/drugsatf...
HIGHLIGHTS OF PRESCRIBING INFORMATION, Revised: 6/2022
To add to CajunJeff's response, the dosages arrived at in Phase 1 testing were not rigorously tested for dose reductions in later phase trials. They sought to have a simple one-size-fits-all dosage recommendation, with dosage reductions in case of adverse events due to gastro intestinal issues, cytopenias, infections, etc.
Since then, there has been a call for more individualized dose management because this stuff is crazy expensive. I think that some middle ground strategy might lead to greater patient comfort while maintaining effectiveness. But this, too, needs to be proven in a controlled study. It's still possible that optimal dosage for PFS is intolerable to the patient.
I found a paper that addresses several issues regarding safety and effectiveness of Venetoclax:
ncbi.nlm.nih.gov/pmc/articl...
Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia
Ther Adv Hematol. 2022; 13: 20406207221127550.
"Finally, permanent dose reductions and temporary interruptions did not adversely impact PFS suggesting that, if clinically needed, a correct drug management should be adopted with no risk of compromising venetoclax efficacy."
This retrospective observational study was done in 221 relapsed/refractory patients, by the way. The median PFS at that time was 38.6 months. Firstline patients usually have a longer PFS than relapsed/refractory patients. But I think the results are hopeful. I'll keep looking for more info that specifically covers firstline, but it might require re-reading every firstline paper to see if one sentence mentions dosage modifications.
=seymour=
Thx for sharing. Ok so I really should have been better prepared and asked more Q's but I didn't have any to hand as wasn't expecting it. The above suggests treatment will be effective and hopefully my neutrophils will recover. Tbh I would love 'time off' after this year. Its been gruelling and 3 months to go. It is my first line of treatment.
They are seeking a balance that will keep your neutrophils up without the G-CSF injections.
My hospital hasn't the got the message about MRD testing.
Well that would be good. Surely you must be tested for MRD? What is your specialist suggesting ?
Looked at few hundred cells from a BMB, CT scan, declared complete response and signed me off to W&W.
Hello Steffi50
I was restricted to 300 mg during up ramp on Venetoclax due to me taking beta blocker. When I saw my CLL Specialist he insisted that I take 400mg after I explained to him that I was on mildest beta blocker as precautionary measure without any issues. I did indeed ramp up to 400 mg and finished treatment ok. After couple of months after finishing Venetoclax my blood pressure started raising, so back on beta blocker and HBP meds. I had never had high blood pressure before. I was also taken off the beta blocker because of low heart rate at 28-32 BPM. Unfortunately or fortunately we are not all the same. Blessings.
I am taking V for a second time. Started at 400 mg and lowered to 200 to deal with neuts being wiped out. Dr. Byrd was very eager to get me back to 400 and I had weekly blood test and ramped back up to 400 in about a month. But as others have said, everyone is different.
And all the specialists seem to have their own ways. I do hope you are coping on 400 now. How long was your remission?
It's been a common practice for decades to adjust cancer drug dosages when certain other cells are affected.
In addition to comments about "it seems sensible to adjust dose based on weight", remember also, our liver enzymes from person to person also vary. So for many, many, drugs not just cancer ones, doctors routinely adjust doses up or down, titrating to *effect*. Depending on how fast or slow a particular person metabolizes a drug that is eliminated by liver enzymes, that affects blood levels.
Not to mention, if one has to be on other medication, there can be an interaction potentiating the effect of one drug versus another. My personal experience with this, was starting simvastatin after stabilized on venetoclax. The simvastatin dose had to be cut; the literature states the venetoclax would have been the likely drug needing to be cut. Instead of autimatically cutting the dose, we watched to see, expecting the venetoclax to start showing more side effects. However, I acted opposite, it was the simvastatin effects that got severe, not the venetoclax ones. And after stopping the venetoclax, testing showed I needed to bump the simvastatin back up. Even though early testing showed the venetoclax was the one that usually got potentiated, it happened to be opposite in me.
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