The flip side of ibrutinib? Atrial fibrillation/flutter

[charliegirl]

I replied to Purrdog a few weeks ago, re the problems he was having with atrial fibrillation (AF) while on ibrutinib. I had experienced some palpitations at that time, but they seemed to disappear shortly after this. However, they returned and I have just had the results of a 24 hour ECG. This has showed a variety of supraventricular rhythm disturbances, including several episodes of atrial flutter ( less common, but similar to AF). Unlike Purrdog I have never previously had any heart problem.

Reviewing the available literature a recent letter to the editor of the journal BLOOD (Julie R McMullen et al Dec 11 2014 Blood 124 (25)) postulates a mechanism, whereby ibrutinib may inhibit a signalling process in the heart which may cause this to happen. They cite an increase an increase of up to a 10 fold increase in the risk of AF with ibrutinib, (the manufacturer reports that 6- 9% are affected, especially if there is a history of previous heart problems)

The manufacturer now mentions the increased risk of AF with the caution, "Consider the risk and benefit and dose modification".

For me the benefits of being on ibrutinib have been huge. Within a couple of months of starting it I had more energy and a feeling of wellbeing than I'd had for two or three years. My brain also seemed to work better. My total WBC has dropped from around 100,000 to 26,000 over the last six months, and Hb has risen from 85 to 110 and so I hope that I will be able to stay on it, probably at a reduced dose.

I am, however, aware that there may be an increased risk of AF/flutter increasing the risk of suffering a stroke. I await my (CLL specialist) consultant's opinion next week, and will let you know what happens then.

[wroxham-gb]

Hope everything works out for you Charliegirl. Take care.

Sue

[SycamoreN]

Good luck with your consultant's opinion next week, Charliegirl. Those of us on Ibrutinib (and other, I'm sure) would like to know the outcome.

[ThreeWs]

Hi Charliegirl,

You are in a tough spot I fully appreciate being one of the early "Lab-Rats" to have received Ibrutinib. I was in a Clinical Trial for only a month or so before I had to have a right atrial ablation due to a very rapid form of tachycardia called right atrial flutter. Context is always a good backdrop for any AE (Adverse Event). Bradycardia (slow heart rate) has run in my family on my Father's side. Dad and I had heart rates at rest of mid 40s. He and I both had congenital heart murmur. His father dropped dead of some heart/stroke event at 44. I believe Ibru acted in me to drop the resting heart rate even further which provoked an escape response into tachycardia (high heart rate) and A-Fib in the process. The right atrial ablation corrected the flutter but I went onto have A-Fib and ended up with a PM (PaceMaker) and AV (AtrioVentricular) Node ablation in May of 2012.

First evidence of my arrhythmias popped up after 1st TX with FR (Fludara and Rituxan) became worse after traumatic failure with Rituxan monotherapy. I would caution anyone who had low heart rate that Ibrutinib might exacerbate heart arrhythmias and or A-Fib. Like you I felt great soon after going on Ibrutinib regarding the effect on my CLL. I have been on Ibru now for 42 months with good quality remission hovering just at but not quite a CR (Complete Response).

I am facing another heart related issue that is likely related to congenital genetic defect. It will be interesting to see if the next generation of BTK inhibitors like ACP-196 will avoid the signaling downside that is probable cause for heart related AEs.

Did you have any known heart issues prior to taking Ibrutinib? Best of luck on how you must proceed.

WWW

[charliegirl]

Dear ThreeWs

Many thanks for this detailed and very helpful reply.

What a story. I'm so glad that the various ablations plus pacemaker have brought heart rhythm under control and that you have been able to stay on IIbrutinib with such a good outcome otherwise.

What you say about slow heart rate maybe predisposing to AF/ flutter when taking Ibrutinib certainly struck a chord with me. My pulse rate has been relatively low for several years - normally around 60 but tending to drop lower at rest. With current problems pulse can drop to 40 - although actual heart rate higher level with not all beats being conducted into the circulation.

Also I found it very difficult to relax while monitored, as I was worried that nothing would show up during tthe 24 hour period. AF showed up when I was dozing or asleep. I suspected that I had so much adrenaline on board that this was speeding up my heart and somehow suppressing the conduction abnormality - which fits with what you say.

I don't have a personal or family history of heart problems although a murmur was picked up a couple of years ago during screening for another trial. Fortunately an echocardiogram was normal.

Pooling this info here is really helpful.

I also hope that next generation BTKV inhibitors will have greater specificity and avoiid this problem.

Good luck and do keep in touch

[charliegirl]

Dear ThreeWs

Many thanks for this detailed and very helpful reply.

What a story. I'm so glad that the various ablations plus pacemaker have brought heart rhythm under control and that you have been able to stay on IIbrutinib with such a good outcome otherwise.

What you say about slow heart rate maybe predisposing to AF/ flutter when taking Ibrutinib certainly struck a chord with me. My pulse rate has been relatively low for several years - normally around 60 but tending to drop lower at rest. With current problems pulse can drop to 40 - although actual heart rate higher level with not all beats being conducted into the circulation.

Also I found it very difficult to relax while monitored, as I was worried that nothing would show up during tthe 24 hour period. AF showed up when I was dozing or asleep. I suspected that I had so much adrenaline on board that this was speeding up my heart and somehow suppressing the conduction abnormality - which fits with what you say.

I don't have a personal or family history of heart problems although a murmur was picked up a couple of years ago during screening for another trial. Fortunately an echocardiogram was normal.

Pooling this info here is really helpful.

I also hope that next generation BTKV inhibitors will have greater specificity and avoiid this problem.

Good luck and do keep in touch

[MsLockYourPosts Passed Volunteer]

Were people with a history of A Fib accepted into any of the Imbruvica trials? I wonder how many cases were possibly caused by Imbruvica, vs made worse by it. As much as I wish I'd bought the stock when it was low, I have never been a candidate for it's use for a collection of reasons, A Fib being one.

Pat