Stopping Imbruvica or reducing dosage after ClonoSeq?

[clladytime]

ClonoSEQ blood test shows only a trace<1 of cll cells. Yay! My doc was ready to stop Imbruvica, which I have been taking the last 5 years. Currently at 280 mg daily. I suggested cutting the dosage to 140 mg and he agreed. Will probably test again at next visit and reevaluate. I'm nervous about stopping the drug altogether and then relapsing at some point. Has anyone dealt with this situation?

[CycleWonder]

I have not started treatment but wow! This must be a big improvement from where you started!

[clladytime in reply to CycleWonder]

Yes it is. 80% infiltration initially.

[lankisterguy Volunteer]

Hi clladytime,

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My CLL expert doctor and my own experience with Idelalisib / Zydelig and Venetoclax / Venclexta would suggest that you are better off pausing / stopping the drugs when you get to MRD-U and then restarting the same drug, later, when you have progressed.

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I remained on both the above drugs and am now resistant to each of them.

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The unproved theory is that maintaining a low level of these drugs allows your body/immune system to evolve resistant clones. Stopping and restarting may result in a much longer time frame until that happens.

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These are only theories.

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Len

[clladytime in reply to lankisterguy]

Lankisterguy, You don't indicate how long you were on the drugs before you developed resistance to them. Wouldn't resistance to the drug have manifested by now (5yrs).?

[lankisterguy Volunteer in reply to clladytime]

I developed resistance to Venetoclax after 6 years, Resistance to Idelalisib / Zydelig took 30 months.

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My doc- Dr. Furman does not like using reduced doses, and his early preference was for single agent Ibrutinib, but is now using more combinations like the one you took.

He now favors taking patients off the drugs once they reach MRD-U, whether that is in year 1, 3 or year 7. And then using the same drug again after the CLL returns. He feels that can yield more years overall survival vs. using continuous treatment at MRD-U

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Len

[clladytime in reply to lankisterguy]

Your posts suggest the CLL will return/progress at some point after stopping meds at MRD-U. Are there studies to back this up? What is the point in stopping meds if only to return later on, perhaps with a vengeance?

[lankisterguy Volunteer in reply to clladytime]

I'm sorry that I can't provide you the proof you are seeking, and I am not permitted or qualified to give you medical advice, you should be consulting with a CLL expert doctor. -

If you read my two replies, you will see that I was relaying my experience and the opinions I heard from my doctor as a possible explanation of why your doctor suggested stopping Ibrutinib. Please note the statements:

The unproved theory is that maintaining a low level of these drugs allows your body/immune system to evolve resistant clones. Stopping and restarting may result in a much longer time frame until that happens.

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These are only theories.

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You can and should choose your own path and accept or reject any other input you wish.

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Len

[clladytime in reply to lankisterguy]

Thank you for your input. I'm just thinking out loud and looking at the big picture.

[AnneHill]

I imagine the test you have had is not available in the uk. I have been taking Ibrutinib for 3 years. I had remission quickly. For 12 months my dose has been 280mg and remission continued.I have been taking 140mg for 1 week. I havent had a face to face appointment for a long time. I have been talking to a consultant and she seemed to think having a break from Ibrutinib would be a chance to see if the pain I have would improve and I have an appointment with a rheumatologist. Unfortunately that is not till November.

I have a choice, stop or have up to 6 weeks break. After 6 weeks I would lose the funding. I can have Venetaclax when required.

I was shocked when I had a different consultant and difficulty hearing him. I lost confidence about pausing and when he suggested dropping to 140mg I jumped at the idea.

I am nervous. What if I am making trouble for myself?

I havent had any tests. I will have a blood test and phonecall in 3 months. In 1 month I will need a bloodtest for immunoglobulin levels. I will ring the hospital nurse and ask them to check for everything else. If there is a change in the remission I will be sorry.

Seems we are both in the same situation apart from testing. Anne uk

[clladytime in reply to AnneHill]

AnneHill, Sorry you are having pain, do you think it is from the Imbruvica? Have you had a flow cytometry test? It also will detect U-MRD and may be available in the UK. It is difficult to make these medical decisions when they have a profound effect on our lives and there is always doubt about what is the best solution.

[AnneHill in reply to clladytime]

Hi, I already had a problem with my back being unstable and I needed an operation.

Despite this I had issues as soon as I began Ibrutinib. Lowering the dose helped but didnt cure the pain completely. I am glad I am seeing a rhumatologist because they may be able to help the nerve pain in my legs and my left foot.

I had some tests done a few years ago but the consultant said that there would always be a hidden few cells when I asked a year ago. I think that makes sense but if I have remission for a while and my numbers rise slowly it will be a relief. I worry I am playing with fire and using myself as a test for how low Ibrutinib will continue to work. I have made a decision and now I have to be patient.

I am hoping this low dose makes a difference. Its only been a week and I am hoping my shoulders and wrists improve. I will ask about flow cytology.

Good luck. You have been taking Ibrutinib for a lot longer than I have and your test is very promising. Anne uk

[clladytime in reply to AnneHill]

Luck to you too!

[Big_Dee]

Hello clladytime

There have been many questions about advisability of stopping Imbruvica when uMRD is reached. I believe there were studies/trials started to determine if Imbruvica can be stopped under your results. I don't think the studies/trials have been active long enough to draw any conclusions. Still your news is great, blessings.

[clladytime in reply to Big_Dee]

Thank you for your blessings. I would feel more confident about stopping if there were studies available concerning this issue.

[Hidden]

Yay is right!!! May it long continue! Be well~Cookie~

[joanne17]

I was on Imbruvica for 6 years. As the drug began to give me swollen feet, nausea and a few other bad side effects my Dr suggested I stop. I've had been off for 4 months but needed to begin on Veneticlax. I tried for two weeks but blood count plummeted. Will begin on the smaller dose again in a week or two. So much is unknown. Scary and a bit depressing but I'm still here and my blood count has been going up again.

[tola2222]

I reached remission on 280mg of Ibrutinib in less than 3 years. I asked and the specialist agreed to 140 mg, but offered no drug holiday. I'm 11g del., among other abnormalities, and I remember Dr. Michael Keating of MD Anderson saying that 11g always relapses (may have been statement about chemo), I'm still afraid to stop altogether.

[Kingfish6]

Glad. to hear this. I'm in the same boat -- don't want to stop but go to 140.

[Jillinill]

Hi clladytime,

I can understand the weight of your decision. We can never really predict the best course as individuals until we see the results.

I took ibrutinib for only 2 years after facing issues of unbearable joint arthritic pain following the forced change from a capsule to tablet formulation. The following month, after a letter from specialists who disapproved of the capsule dissapearance, capsules were again offered 1 month later, but the damage was done. Pain improved after returning to capsules but never completely went away, and I continue on Celebrex to this day.

I took only 280 mg due to my low body weight and continued at 280 mg until 1.5 years, then dropped to 140 mg for several months, then 140 mg every other day due to unbearable muscle pain and brain fog.

Unfortunately my bad specialist, who was always out the door in 3 minutes or less disapproved of the MRD test. I'd been stable at ALC 3, and because of increasing pain and brain fog, we decided to stop ibrutinib at 2 years. The next month, my pain and brain fog improved dramatically.

I remained stable at ALC 3 for 1.5 years before I started to double monthly, and transferred to another specialist at Northwestern. 2 years after stopping ibrutinib, with ALC 100 in March 2020, the pandemic started. I knew BTK treatment would kill any chance of any appreciable vaccine response with emerging data. We tried to delay 2nd treatment till after vaccination, but I had months of constant UTIs with 0 Neuts so we started acalabrutinib at 2.5 years post ibrutinib hold.

I may double quickly at 1.5 years post ibrutinib remission, but also responded quickly to the 2nd BTKi. As I had some issues with neutrophils remainung stuck at 0 for several months, with low platelets and hemoglobin, we dropped from 200 mg to 100 mg dose, and all issues improved on the lower dose. After 5 months on acal, I was back in normal ALC range. We were glad to see a fast response. After 14 months on acal, and stable at ALC 1.5 for the past 6 months, I just had an MRD test with 3% cancer cells.

I really wish that my bad specialist had run MRD prior to stopping ibrutinib so I would understand my first remission better, but we will continue on acal until MRD is reached, but not past that point.

I'm not a clinician and only offer my own experience.

I hope you continue a long remission following your decision.

Jill

Trisomy 12, Unmutated

[clladytime in reply to Jillinill]

Glad things have improved for you and that you switched to acal after imbruvica. Thank you for your input and wishes!

[Zsuzsika]

I am happy for you that you will be able to go off of your medication. I have been on Imbruvica for 5 months. I am getting dizzier more frequently and has now fainted three times. Had that happened to you?

[clladytime in reply to Zsuzsika]

Sorry you are experiencing serious side effects from the Imbruvica med. Hopefully your doctor is aware of this and may switch you to another treatment or med. I have never had fainting spells or dizziness while on Imbruvica. Something else could be causing your symptoms and your doctor should be looking into that as well. Good luck.

[Zsuzsika in reply to clladytime]

Thanks for letting me know. I am still very happy for you.

[country76 in reply to Zsuzsika]

Do you monitor your blood pressure? My blood pressure shot up while taking Imbruvica.

[clladytime in reply to country76]

Blood pressure is OK.

[country76]

That is great to hear!! Very promising. I started Ibrutinib in 3/2019 and then switched to Alacabrutinib. What is your WBC? Why did your doctor do the Clono Seq?

[clladytime in reply to country76]

I was MRD neg on 2 previous blood tests and rest of blood work was good. The ClonoSeq is a more advanced test to detect CLL cells in the blood. He wanted to do these tests and then possibly take me off Imbruvica. I didn't go off the med but reduced dosage from 280 mg to 140 mg daily. I may go off completely if MRD neg continues on the next test.