Acalabrutinib Side Effects, Arrhythmia, Cardioversion and starting TGR-1202

[Ramses]

Today I see my oncologist to, I hope, plot a path forward. Acalabrutinib has worked wonderfully for me, but at some point before the beginning of this calendar year, I developed an Atrial Flutter, which took three months to diagnose and only seconds to fix.

At the point of diagnosis, I stopped the Acalabrutinib, and last week I had the cardioversion to shock my heart back to normal rhythm. The big question is: Is the arrhythmia a side effect of Acalabrutinib or a natural consequence of my age?

I am 83 years old and the two cardiologist I have seen have leaned toward my age as the culprit. They point out that over 10% of people my age have such issues with the atrium. According to my oncologist, who is, quite naturally, concerned that the investigational drug is responsible, 3% of people in the trials have developed Atrium issues. He suggests that the normal sinus rhythm would not be sustainable if I stay on the drug.

So, there we have it. Rather oversimplifying the issue -- I do not have an age distribution of those in trials with Acalabrutinib: 3% of people on the drug and 10% of people my age develop A fib or A flutter. Without knowing the ages of those on Acalabrutinib who develop arrhythmia, where do I place my bet?

[sundancing]

Ramses, Very glad to hear that your cardio took seconds to fix. May you have good advice going forward. I am a 68 year old CLL female on my 6th month with Acalabrutinib. My docs at the NIH told me from the very beginning that A fib or A flutter were possibilities on this drug. But I have had slight experiences with each before I even started on the drug. For at least 10 years now. So, with me, it is probably a matter of age, although I’ve had CLL for 22 years now and we don’t know what part the condition may have played overall. There seems to be little clarity on the issue! Good luck with your oncologist visit today, all best wishes, and keep us posted.

[tpetro in reply to sundancing]

Hi Ramses

I started the Stanford acalabrutinib trial at age 67 and I am nearly 69 now. I have not had any heart issues only minor joint pain...I take a statin for high cholesterol which totally under control...I hope you find the solution to your heart issue and a therapy that works for you...luckily there are choices these days❤️

Terry

[jaysearch]

Hi Ramses Really encouraged that you found relief. I'm 75 yr old male who has been on Imbruvica for nearly 6 mths (1st time it was 4 mths). Just diagnosed with A-Fib. I can feel the heartbeats, but not the flutter they see on the ECG. Sometimes erratic, and sometimes it lasts for 15-20 minutes. How did they fix yours - so I can ask my Cardio Dr? Glad to hear you are doing well. Dr gave me Diltiazem, but it doesn't seem to be very effective. Jay

[Ramses in reply to jaysearch]

My cardiologist did a cardioversion, shocking the heart back into normal rhythm. It has now been a week and the "fix" has lasted. He suggested that I get a device, Kardia, which can couple to my iPhone and from two fingers on each hand, gives me an approximate ECG, I suppose the thought is to identify A Flutter if it comes back. I plan to send the cardiologist a month's worth of readings after I acquire them.

[jaysearch in reply to Ramses]

Thanks for the info. Now I can have another discussion with the Cardiologist. Jay

[tsvieps]

Imbrutinib is known for this issue, but for most it took a while to develop. Acalabrutinib has shown less of this adverse effect so far, but it also has not been used as long. You might discuss with your oncologist and cardiologist the possibility of finding a dose that is effective and yet dose not trigger Afib. My oncologist has some experience with such compromises.

[Ramses in reply to tsvieps]

That's an interesting suggestion and an option I had not thought of. I may send my oncologist an email and raise the question. Since Ibrutinib is available commercially, I would think with this drug such tests could be done by any individual doctor. However, as I'm sure you know, Acalabrutinib is available only though a trial, and i would wonder if the sponsor would support experiments, e.g., make the drug available, with other than the recommended dosage. I fear changing the protocol in any way raises issues and poses unanswered questions, which may make the option of a reduced dose not accessible to me. What do you think? Am I missing a point?

[tryandtry]

Hi Ramses

It's obviously your choice, but apparently a lot of people have had Afib with Imbruvica (it's too early to tell with Acala...), and they've managed to stay on Imb. by closely watching the Afib, and countering it with "other measures" (whatever that means, I guess they use blood-thinners, rhythm pills, etc - I'm no cardiologist, but from previous posts, it apparently can be done).

I have a similar problem. After 15 months of successful Imbruvica use, I developed Afib, which quickly led to Mitral regurgitation, and mitral valve repair. I had a cardioversion, and am now back in rhythm, taking Tikosyn to try and stay there. I'll soon start Acalabrutinib, and hope the reported lower incidence of Afib will "play-the-odds" for me. Otherwise, my choices look pretty limited.

BTW, I had to reduce my dosage of Imbruvica to only 2 pills shortly after I started it, due to problems with several of its listed side-effects. Have you seen much need for people to have to reduce the dosage of Acalabrutinib due to severe diarrhea, bleeding, rashes, etc?

Good luck! Treat the CLL; there are a lot of Cardiologists out there, and they apparently can usually handle Afib, somehow.

Gary

[Ramses]

Given that it is most likely that my Atrial Flutter was a consequence of being on Acalabrutinib, I am moving on to another clinical trial with another "brand new" drug.

About four years ago, I failed a trial on Idelalisib, so I am eligible for a Phase 3 trial of TGR-1202, which is also a PI3K-Delta Inhibitor, purported to have far fewer side effects than Idelalisib.

Are there any others with like experiences or any who have comments on TGR-1202?