If you cut back on the amount of Venetoclax from 400 mg to 300mg, do you have to extend the the amount of time that you must remain on it?

[ronsolo306]

Venetoclax reduction in dosage

[SofiaDeo]

Boy, this is an interesting question. IDK if anyone has studied this. I guess it would depend on if the reduced dose was affecting the CLL cells as much as it was affecting platelets, RBC's, liver function, or whatever reason necessitated the dose reduction.

[Newdawn Administrator]

In simple terms, I think it must depend on the reason for ‘cutting back’ on dosage. Is it due to adverse events, neutropenia etc. Also, has uMRD been achieved and what’s the residual disease level? If the detectable disease level remains significant, I can’t see any specialist stopping any level of dosage (unless it’s a time limited trial of course).

I’m now on Venetoclax monotherapy and have achieved two consecutive undetectable peripheral blood results from flow cytometry. If my bone marrow confirms uMRD, I’d actually hope for a reduced dosage for the required duration of the trial. However, I know that will only be done for persuasive clinical reasons such as adverse events.

What is your situation ronsolo that prompts this question? What advice has your specialist given? Your previous posts suggest you’re doing well on V after only a short period of time. Is this a ‘I was just wondering’ question? It’s a sound question actually.

Newdawn

[SofiaDeo in reply to Newdawn]

Yes, because I thought my CLL specialist said something along the lines of "only needing Venclexta Tx for 6 months" 3 days after I was started in hospital. I had a 10% cell reduction overnight, my cell count rose slightly the next day but spleen size reduced, then cell count went down again. It was early in the AM, I was barely awake & I may have misheard him. I have noticed some people here are on 200mg instead of 400mg. I am thinking about asking specialist what experience/effects he's seen on lower doses. Like the imbruvica (and virtually every other med I've had to take in my life), I seem to respond to lower doses & don't tolerate high doses.

[Naka in reply to Newdawn]

Newdawn have you been able to stay on the full dose of 400mg? May I ask how long do you have to take the Venetoclax on the trail you're in?

[Newdawn Administrator in reply to Naka]

Yes I’ve remained on full dosage for nearly 21 months without a problem.

On the Flair trial I’m on, it’s required that you remain on the meds for the corresponding time that it takes you to reach remission so it would be 18 months in my case.

I suspect I reached it earlier but COVID has delayed all the testing and normal oversight.

Regards,

Newdawn

[Fowey2009]

My husband started 400mg venetoclax in Sept 2019. In Oct 2020 he became severely neutropenic so Venetoclax stopped for a week whilst he had iGCSF injections . Started again on 300mg, neutropenia continued so reduced to 200mg at the end of November. Been on 200mg ever since - neuts back up to 2.37 although lymphocytes still 0.78. Suggestion is that he will now stay on 200mg until the end of his treatment in September this year (2 years treatment being funded in the UK).

On a separate subject, he had his covid vaccination on Saturday and less side-effects than he normally has with the flu injections.

Beryl

[thb4747 in reply to Fowey2009]

I have a very similar story. I started the ramp up in April 2018 but, because of neutropenia and diarrhoea issues, I reduced to 300mg in September 2018 and 200mg in November 2018. I’ve stayed at 200mg ever since and will remain at that level until April 2022. I’ve been in remission since November 2018.

[dvd1955]

I think it depends on why you need to reduce the dosage. I am on only 200 mg per day for twelve months. The reasoning for me is interaction with a blood pressure medicine I take, which is a moderate CYP3A inhibitor. The Venclexta prescribing information says to reduce Venclexta by 50% in this case.

[Teegolf47]

I think the answer to this question is WHY the dose reduction and how are you responding to the drug. What you have to remember that the dosage that you get, after a drug has been approved, is the dosage that was used in the Clinical Trials. They key factor is 'what is the optimum dosage that will control the disease and not have unmanageable adverse events' For Venetoclax it was determined to be 400mg daily. This may not be the RIGHT dose for everyone, but generally it is the dosage that is used for patients to start.

Now to give you some personal experience insight on what happened to my dosage levels on Venetoclax. I started Venetoclax in May of 2018. At the time I was also on Ibrutinib (which I had been on for almost 5 years but was slowly relapsing). After the initial ramp up my blood numbers were all in normal range and at 5 months I only had .3% residual CLL cells thru an MRD test. At 11 months I was MRDu tested at MRD5 level (less than 1 in 100,000 cells). This was tested multiple times after that and it was still MRDu, but the issue I had was ADVERSE Events. After about 18 months we could not manage the diarrhea. Since I was in an Investigator Clinical trial at the time, my medical team decided to lower the dose of Venetoclax. We finally got to a dose where I had no more Adverse Events. That dose was 100mg daily. Now keep in mind that this was AFTER I had reached MRDu, so the heavy lifting to get me to that point had already been done. MRD testing done after I had reduced the dose still showed no evidence of disease.

Since there are no standards as to when or even if you should stop Venetoclax once you reach MRDu, that has to be decided either as part of a trial you may be in, or in conjunction with what your medical team and you decide. I know people that are still on Venetoclax after 4 years. I know some that have stopped (after reaching MRDu) at 12 months, 18 months, and 24 months. For me, I stopped 19 months after I became MRDu (30 months total on Venetoclax). Was that the right thing to do? Who knows. Several top CLL doctors say continue on. But on the other side some top CLL specialists say, 'why beat a dead horse', and lets stop the treatment. There is NO consensus on what to do. The latest papers at ASH 2020 report that if you stop Venetoclax and then relapse, there is data to suggest if you restart it you will once again respond. So that may happen in my case.

To really test this issue you would have to have a Clinical Trial where different dosage levels were given, or a trial where they reduce the dosage after you reach some level of MRD. There are still a lot of unknowns.

Terry

[mickimauser11]

Not necessarily it depends on your response I know s o who reduced to 200 mg and still achieved the goal within the time span which was stated before

[Canuck901]

As long as you can stay on at least 100mg of venetoclax it has had very good results

Not everyone can tolerate the full 400mg dose

2 years is the usual time even at reduced dose