If your side effects of a BTK inhibitor become intolerable (even after a dose adjustment) while your blood counts has kept substantially improved, what was your experience with interrupting the medications until the disease starts coming back vs switching to another medication immediately (BTK or otherwise) ?
Switching medications vs interrupting the trea... - CLL Support
Switching medications vs interrupting the treatment
Written by
MikeOr
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34 Replies
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lankisterguyVolunteer
Hi MikeOr,
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Since you asked for direct experiences. I don't have a simple answer to your question, but here is my complex experience.
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In 2015 when my MRD and ALC / Lymph# began to rise noticeably I switched from Zydelig/Idelalisib to Ibrutinib/Imbruvica in one day, but the Ibrutinib caused a itchy rash and did not seem to reverse the rise completely. So we stopped Ibrutinib after 9 months and had progression in 6 months to needing treatment.
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In 2016 I started Venetoclax / Venclexta and did well until late 2021, but MRD started accelerating up to 1.3%, so we added Calquence / Acalabrutinib in January 2022. So far no side effects, and I will have a MRD test in April.
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After listening to several CLL expert doctors, I believe most would recommend that a patient that found Ibrutinib / Imbruvica intolerable (severe side effects) try a fast switch to Acalabrutinib / Calquence.
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While if the patient was progressing on Ibrutinib / Imbruvica ( ALC / Lymph# rising or growing nodes & spleen) they would stop treatment and wait for progression and then start 3 months of Obinutuzumab / Gazyva and then ramp up Venetoclax.
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Len
Hi Len
Does the time on a BTK impact the calculus? In other words, would the patient who was having difficulty 30 days in be treated differently from the patients who has been on BTK for 1-2 years? Perhaps the longer term patient might have a better chance of remaining in remission if all treatment was stopped?
Best
Mark
Hi Mark,
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I agree, with your hypothesis.
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Most patients would develop Ibrutinib / Imbruvica side effects early (e.g. first year) and before there was a significant reduction of ALC / Lymph#. So a quick switch to Calquence / Acalabrutinib would be a continuation of that treatment.
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But resistance to Ibrutinib due to mutation would likely occur much later ( year 2 or beyond ) and after the ALC / Lymph# or MRD had bottomed out and started to rise again. So stopping the first treatment and waiting for progression to start the next treatment with Venetoclax / Venclexta would be more likely.
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My sequences & treatment pauses were non standard, and each case was discussed thoroughly with Dr. Furman. We were on new unproven ground, learning together. I'm not certain he would do some of them the same way today.
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Len
I’m confused. Sorry. Can you answer possibly as if MRD is not part of the question/example.
I'm not certain I understand the question. -
More simply if a BTK inhibitor (Ibrutinib) is working to control the CLL, but that BTKs causes side effects, try a different BTK (Calquence) with no pause
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If a BTK is NOT working to control the CLL, switch to a BCL2 inhibitor like Venetoclax, after a treatment pause and a 2nd progression.
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Len
And a third scenario - If the Ibrutinib worked but causing too many side effects AND labs were in normal range could someone “interrupt” treatment (stop/enter another w&w)?
That would be up to the doctor and patient, and exactly when having MRD test results to break the tie on whether it is better to continue treating or stop treating. (But you told me to leave the MRD test out of the explanation LOL). Len
No simple answers from you! :). But it appears you believe MRD = possibility of stopping treatment. Not MRD = continue treatment. If I knew how to post a poll to see how many are not MRD but in a second or third w&w I would!
I just watched a video today of Dr. Wierda from MD Anderson talking about how he uses MRD tests exactly that way but also admits that there is no reliable data that it is proven yet. Its about 35 minutes to 40 minutes into this:track.consultant360.com/?xm...
Len
Appreciate it.
MRD status is a proxy for anticipated remission length. I expect that this will be refined to include relevant prognostic markers when we know them...
MRD tests? Is this bone marrow tests or PET/CT scans? Just wondering
If Lymphs# (ALC) Absolute Lymphocyte Count range 1.00 to 4.80 x 10^9/L are in the normal range, a CBC+dif test cannot tell how many of those are normal B cells and how many are cancerous CLL cells.
When the Lymph# / ALC is above 30 x 10^9/L the doctors assume that most of the 30million are CLL cells.
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The MRD test counts how many of those cells are CLL cancer.
(note: the MRD test can be done on blood or bone marrow and for most people the results are very similar).
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My latest CBC test in 2022 said that they found 1,100,000 Lymphs in one liter of my blood.
The MRD test said that 1.3% of those were CLL cancer, or 14,300 CLL cells.
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In 2020, I also had 1.1 million cells in a CBC test but the MRD test found NO CLL cells in that sample. So I was MRD -U (Undetectable or Unmeasurable)
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If I stopped treatment with MRD-U I would probably have a longer time until my CLL cancer came back. If I stop with 1.3% cancer cells, it may come back a little quicker. So getting the MRD to 0 or very close to 0 is a little better.
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Len
Thats kind of what they did to me. Took IB for 1 year, caused a fib and increased my blood pressure so I had to add a third blood pressure med. They stopped it in March 2020, and WBC and Lymphs creeping up, now WBC up to 140 (it was 340,000 when I started IB) So 2 years and they are wanting me to start O plus V.
I just thought I would add my experience and wonder if you had any input on it. I was on ibrutinib for about 1 1/2 years (2/3 dose) but stopped for six months and did notice I had Afib but was still in remission when I switched to acalabrutinib (1/2 dose) and am completing 1st year on it. (I had obin and gazyva previous to ibrutinib but it only gave 6 months of remission). So far no major side effects and very few afib occurrences (when stressed or after eating too much salt). I am wondering how long i might achieve remission for if I stop acalabrutinib after being on the half dose for almost 2 years. I want to feel free of the side effects. (Hard to twist body or be too active without some pain (feels like muscle pain) and fatigue. Grateful for any thoughts. My doctor says very little.
Hi onu1tadi2,-
I would love to help you, but I am not medically trained and this entire discussion is starting to approach providing medical advice, which we legally cannot do.
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I can tell you my experience and give you links or quotes from what CLL experts have said after looking at statistics for many patients. But we cannot recommend what you should do.
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So the best course is to get a 2nd opinion from a top CLL expert doctor. cllsociety.org/toolbox/cll-...
or you can get a free 2nd opinion here cllsociety.org/cll-society-...
edit: I just saw that you are in Canada- and the free 2nd opinion may not be available to you. I think we had one Canadian get it, then a different person was denied due to insurance problems. You may want to try, and fill out the form accurately to see if they will accept you.
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Len
It is not easy to switch doctors in Toronto where I am. Besides acalabrutinib is so new there just isn't enough certainty about dosages, effectiveness or strategies. My oncologist is incredibly uninterested in her work and uninformed. But personal experiences here on this forum are very valuable to me, with so many intelligent people. Thanks for the links and I wish you all the best.
Hi onu1tadi2,
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That seems strange since there is only one dose form of 100mg and it is taken 2X per day 12 hours apart. see den8dhaj6zs0e.cloudfront.ne...
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Here is a video explanation of the head to head comparison vs. Ibrutinib:
onclive.com/view/head-to-he...
onclive.com/view/acalabruti...
and text versions of the same study:
ascopost.com/news/august-20...
ascopubs.org/doi/abs/10.120...
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Len
Hi again. I am just taking one of the pills a day. I started that way. I get my acalabrutinib, or Calquence directly from Astra Zeneca, as it is not available through our health care system and hence they give it to me on a charitable basis I guess. Luckily my regular oncologist was away, and the replacement, more engaged with his patients, got me onto the Calquence. He thought it was OK to do one a day instead of two. After all the two a day is based on what they used in the clinical trial. They will always use more not less to make sure a trial gets results. However, I would rather take two thirds but not possible with only 100 mg pills available.
Hi Mike,My BTK story was with Acalabrutinib. After 2 years on full 200mg dose with a couple of 2 week drug breaks, I opted for a dose reduction to 100mg. to ease the relentless side effects. My labs continued to improve then held in normal range. Sfx did not improve enough. After 3 1/2 years total on Acalabrutinib, I stopped treatment and declined offer to possibly switch to venetoclax. My labs have remained normal for 2 more years. Sadly, I have recently noticed lymph nodes in my neck, pretty clear sign of recurrence, but still a pretty good run for not having reached mrd. Will w & w again to decide on next step.
Hi. Can I enquire why you reluctant to take the venatoclax? I am planning to get a flow cytometry test if possible (not available in Canada, but perhaps US) to see about minimal residual. If it is good then I want to go off the acalabrutinib after a two or even just a 1 1/2 year stint. I have heard people go off and on it, taking "holidays." I took a six month holiday and was able to restart it, with no progression happening. But I went from ibrutinib to acalabrutinib at that time. I will try to see if an oncologist can tell me if I can take periodic holidays from acalabrutinib and barring progression go back on the same drug again. Of course Astra Zeneca who gives me that drug is not willing to allow anyone to take more than one break..i think a three month one -- before cutting them off.
Yes, I discussed at length with my primary oncologist and my Acalabrutinib clinical trial team. Both seemed to concur that either choice was a good one. And since the btk worked so well for me (except for the sfx) that if I stopped treatment I might get a decent remission and by the time I needed treatment again, there might be other options. They left the choice to me and were very supportive of my decision.
Mind sharing your markers? Congratulations on the 2 years and that Acalabrutinib worked for you.
This is definitely something that varies depending on your situation. Some people have taken medication holidays after treatment. In my case, I'd risk having the disease roar back because I'm 17p deleted. I had to be off meds for a couple of weeks even because I was having issues with bleeding and even though I had a normal WBC, I went back on as soon as I could. I definitely would ask a consultant and make an informed decision if I were lower risk and in the position to consider that approach.
Mike OR,,, your question is timely for me. Because, I am currently stopping my BTK inhibitor and we’re trying to decide what to do next. I have been taking IBRUTINIB 280 mg,,,, for two years plus. And as your question asked,, my side effects have become bad enough so that my doctor thought a change was called for.For informational purposes my history is that I was diagnosed in 2012,and did a year of watch and wait and then went on to a trial. The trial ended but I continued on the medication which was REVLIMID® (lenalidomide), . My treatment is being done at Moffitt Cancer Center by a specialized hematologist and his team
So, your question is about switching. And if you would like ,I can PM with you about what happens in the future, or I can post it here.
The next step,,, is to get a CT and a bone marrow biopsy to see exactly what’s going on with/ inside my body. And then make a determination on either watch and wait or a switch in medications. This will depend on the results from the CT and bone marrow.
This is not an answer to your question but if you’re interested you could follow my progression in real time. Just let me know if you want to private message.
Good luck and good health
Michael
Just about to do that. Stopped Ibrutinib last week. Will be assessed end of March. I really wanted to know how long will it take before you begin to feel better.
I was requiring a wheelchair to get thru the airport due to the pain & fatigue of Acalabrutinib. A month after stopping, I was beginning to walk 3 mile forest preserve trails, back to my normal arthritis pain.
Just about to do that. Stopped Ibrutinib last week. Will be assessed at the end of March. Wanted to know how long does it take before the medicine leaves your body.
Ibrutinib has a half life of 4 to 6 hours, so it should be undetectable after much less than a week. It can take a few months, however, before your body recovers and you begin to feel better from the lack of side effects.
Neil
I have had no serious side effects for the three years I have had meds for CLL, from obin and gazyva to Ibrutinib to acalabrutinib. But I never think of taking long walks. I go for 20 min walk, I make sure I rest when tired, I do spend lots of time working on computer, but baby myself in other ways. No rashes, blood problems, but some afib from the ibrutinib (almost gone with the acalabrutinib), and i eat little meat, lots of veggies. And vit C pills and D. I am 76, and 13 del. Feel lucky not to have had any emergencies. But each person is different. So many very different symptoms reported here.
onu1tadi2,My decision was more about freedom to travel and enjoy life again while I still could, rather than anything against venetoclax. I stopped treatment mid February 2020 with a year full of world travel planned. Of course the world shut down a month later. I try not to dwell on the thought that had I gone on V I'd have reached Umrd while in isolation and probably not now be facing recurrence. Life can be perverse.
Thanks for reply. Yes so many plans are disrupted. I had planned a project in Europe, but now it is wasting away. Not sure what the U stands for in mrd. Wonder if 2 years on half dose (acala) will achieve long drug-free remission. Each person seems to have an entirely different or unique experience and outcome with these new drugs.
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