I have irregular heartbeat and treatment

[Test_Tech]

I have irregular heartbeat. Is it true that I can't take Ibrutinib or Venetoclax to treat my CLL. Is anyone familiar with this in the community.

Thank You

[lankisterguy Volunteer]

Hi Test_Tech,

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Your best path is to work closely with a CLL expert doctor and have them consult with an equally expert cardiologist.

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I have heard some expert doctors say that the AFIB that some patient experience on Ibrutinib does not occur with every patient and possibly can be managed with medication when it occurs.

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But in general I would guess that your CLL expert might lean towards Venetoclax to reduce your risk and possibly allow for shorter treatment if you get to U-MRD.

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You need to go over this medical discussion with your doctor and should not make any decisions based on things you get from this forum.

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Len

[cajunjeff]

This would definitely be something to discuss with your doctors.

There is not a ton of data on the new drugs like ibrutinib and venetoclax. For some patients, fcr (chemo) is still the first treatment of choice. Generally speaking, people who are fit and under age 65 and have mutated IGHV, do very well on fcr.

The thinking among some is that the new drugs will eventually make chemo obsolete for cll. Just in the past year or so, ibrutinib has emerged as the first choice of treatment for a large population of cll patients.

The data on ventoclax are much less mature. While ventoclax is seen as a more powerful drug than ibrutinib, its not prescribed front line as much as ibrutinb. That might change soon.

About ten percent of those who take ibrutinib will develop afib. That's a very high percentage for a significant side effect like afib. It is thought that the ten percent risk is less for those who do not have preexisting heart problems, higher for those who do. My lay person intuitive presumption would be that if you have existing afib, ibrutinib might exacerbate it.

That might lean your doctor to fcr if you have the right markers or to venetoclax with or without another drug like gazyva.

Another option might be acalabrutinib, a drug that works just like ibrutinib (they inhibit btk which lets cll cells die), but is thought to carry much less risk for cardiovascular issues such as afib than does ibrutinib.

In summary, I wouldn't say you absolutely could not take ibrutinib because of your afib, you could take it and take other meds to manage your afib. But your afib might push your doctor to other options. Venetoclax may soon replace ibrutinib as the first treatment of choice for cll anyway.

[rubberlegs68]

I developed afib while on ibrutinib and began taking dofetilide(tykosyn) while continuing the ibrutinib. This seemed to keep it in check with no discussion of stopping the ibrutinib. The tykosyn was contraindicated with another medication being recommended to me so I chose to have an ablasion procedure to fix the afib and stop the tikosyn. So far so good although I have now developed high blood pressure. Unknown whether the ibrutinib is causing that.

[cajunjeff in reply to rubberlegs68]

I am just curious, did you have any pre-existing heart issues at all before starting ibrutinib? I think the risk of developing afib on ibrutinib is somewhat greater for this with preexisting heart issues.

I would expect with Calquence (acalbrutinib) being approved, anyone with any preexisting heart issues at all would be put on calquence before ibrutinib.

Ibrutin raised my blood pressure and I worry about the long term cardiovascular effects of continuous ibrutinib usage might be.

At my next visit I am going to ask my doctor if he thinks I should switch to calquence.

I think there is a good chance ibrutinib triggerd your afib and is contributing to your high blood pressure, of course I dont know. It might be worth asking your doctor too if a switch to calquence is warranted.

I thought I read Dr Furman write somewhere that the effects of ibrutinib are not irreversible. That's why I want to ask my doc if thinks switching to calqeunce would help my blood pressure and reduce the risk of unknown long term heart issues associated with ibrutninb.

[rubberlegs68 in reply to cajunjeff]

I suspect that I have had irregular heart beats for sometime although nothing was ever confirmed with testing. Episodes seemed to come post exercise but were not detected through testing. I do have a very strong family history of heart problems. My blood pressure has always fluctuated and I have felt that was due to a severe sleep disorder that I have always had. I will ask my oncologist at next visit although that isn't until mid February. I don't know anything about calquence but am curious. I am on a reduced dose of 140mg of ibrutinib due to episodes of neutropenia at higher doses.

[cajunjeff in reply to rubberlegs68]

Ibrutinib was the first btk inhibitor. Its over my head, but ibrutinib binds to a btk protein in cll cells. The btk protein keeps cll cells alive and ibrutinib inhibits btk which allows cll cells to die.

There are lots of inhibitor drugs for all kinds of illnesses. They can have what is called off target effects. With ibrutinib the of target effect is that for some of us it causes afib and or raises our blood pressure.

Calquence (acalabrutinib) is a second generation btk inhibitor. It is thought to be more highly targeted to only hit cll cells. Think of it like a more highly guided missile. Ibrutinib would be the missile that hits the ISIS camp, but also blows up part of the restaurant next to their camp. Calquence would be more highly targeted and hit the ISIS camp only and sparing the restaurant. Its admittedly an imperfect metpahor, reflective of my imperfect understanding of how these amazing drugs work.

Calquence just got broader FDA approval. Calquence is thought not to have the off target effect of causing afib or high blood pressure that ibrutinib does.

There is some thought that the effects of ibrutinib might be reversible. For you and I, that could mean if we get off ibrutinib, our blood pressure might go lower.

Its worth a conversation with our doctors to see if we should switch, at least in my opinion. I suspect for me the answer will be to stay the course with ibrutinib and not rock the boat that is working. If he thinks calquence will work as well for me with less side effects (off target events), maybe he switches me.

[rubberlegs68 in reply to cajunjeff]

Thanks for the info Jeff. I'm pretty sure my oncologist will feel that ibrutinib is working so doubt that he will want to switch course at this time. Unfortunately I never had the tests for genetic markers prior to undergoing 6 rounds of fcr in 2013. This is my 2nd oncologist at the same cancer center and for some reason neither of them puts much emphasis on this which I now disagree with. If I were to change course treatment wise I would want to have this information. Not that it would alter things for me at this point but more so out of curiosity. My doubling time prior to initiation of fcr indicated an aggressive form so fcr was the recommendation for me. I'm curious if ibrutinib was in trials at that time as I may have opted to go that route and skip the hardcore regimen of chemo. At this point ibrutinib at a low dose is doing wonders at keeping all of my numbers in check.

[cajunjeff in reply to rubberlegs68]

I doubt my doctor changes Ibrutinib for me either, but it’s worth a talk. There is emerging concern about long term cardiovascular problems with ibrutinib. Supposedly acalabrutinib has same efficacy of ibrutinib with less cardiovascular risk so I am going to ask my doc in January.

[HopeME in reply to rubberlegs68]

Hi Rubberlegs68:

Have you decided on seeking that second opinion from a CLL expert? Now is the time to do so before you need to make a treatment decision. I know you have considered this in the past. It’s well worth the effort. I hope you are well.

Mark

[rubberlegs68 in reply to HopeME]

Hi Mark, I am doing pretty good on the ibrutinib other than the possible cardiac related issues and will stay the course until that changes. Dr Pagel in Seattle is someone I would try and see if possible. He's pretty renowned and not to far away. I would like some testing to see what my makeup is prior to starting another treatment though. Thanks for the well wishes and hope the same for you.

[Test_Tech]

Thank you all for replying to my inquiry. I have some guidelines to help me.

[thb4747]

I have an irregular heartbeat also and had AFIB in 2008. I’ve been taking Venetoclax (currently 200mg daily) for 19 months without any issues. I understand it is a problem more associated with Ibrutinib. Interestingly, Venetoclax has just been funded for second-line treatment in New Zealand. Ibrutinib is not funded here and costs about $US4000/month I believe. Venetoclax is free.

[Test_Tech in reply to thb4747]

Thank you thb4747 for the reply. I have appoints in the next three weeks to see three different oncologist and I will be discussing treatment options. I'm thinking Venetoclax would be right for me. I also have an appointment with my cardiologist to discuss options to deal with the AFIB ie. Ablation procedure or if absolutely necessary a pacemaker if I am eligible.