CLL, Imbuviva and AFIB

[BobTerry62]

I am 81. Two years ago I started on imbrubica and about a year in I had afib which is a known risk for this drug. I was advised to and did consult with my cardiologist before commencing treatment with Imbruvica and was told if I get afib we will treat it. That's what happened but it took three months to get back to a normal life. Note that there are studies that now can better determine if a patient is more likely to have this adverse side effect. So, be sure the cardiologist is up to speed on all the recent research on this side effect on CLL patients taking imbruvica. Good luck and good health to your dad. Bob

[AussieNeil Partner Administrator]

Thanks Bob, for sharing your experience with ibrutinib and AFIB in a clearly titled post.

I've added your reply to this post, where I think you meant it to be.

healthunlocked.com/cllsuppo...

I've also edited out your last name to maintain your privacy, given you've posted so it can be found by anyone in the world searching for others on ibrutinib experiencing afib, rather than just our community. Let me know if you want me to make your post private to our community.

This post explains how the Share setting changes who can find and read our posts: healthunlocked.com/cllsuppo...

Neil

[BobTerry62 in reply to AussieNeil]

thank you.

[BobTerry62 in reply to BobTerry62]

I have been on Venclexta for two years and recently reduced the dosage to three 100mg pills once a day. Any thoughts on other alternatives once I need another alternative?

[AussieNeil Partner Administrator in reply to BobTerry62]

Hi Bob,

There's a recognised need for new treatment options once you've had BTKi based therapy (acalabrutinib/Calquence, ibrutinib/Imbruvica, zanubrutinib/Brukinsa), then BCL-2 based therapy (currently venetoclax/Venclexta).

I don't know if you noted from my other reply this mention of how "Zanubrutinib was also associated with a substantially lower rate of atrial fibrillation (2.5% vs 10%) compared with ibrutinib in the ALPINE trial." So it might be an option to switch back to this later generation replacement for ibrutinib, perhaps on a lowered dose if your CLL is well under control.

Also, there are several second generation BCL-2 alternatives to venetoclax in clinical trials, so if you develop resistance to venetoclax, it may be possible to switch to one of these if it is approved or available to you through a clinical trial. Younger people might opt for CAR-T or a bone marrow transplant, or even an older chemo treatment, specialists prefer not to go backwards with treatment options.

Neil

[BobTerry62 in reply to AussieNeil]

Terrific information and thank you so much for taking the time to share it with me. Perhaps I will ask about this with my Oncologist at the end of the month. bj

[5214 in reply to BobTerry62]

I had great luck with Venclexta. It took my White Blood count down in a year and half I just got tired of all the water drinking and staying up going to the bathroom all night so I stopped. Just started Calquence so I’m hoping for relief now.

[AussieNeil Partner Administrator in reply to 5214]

Per the venclexta site, with my emphasis: venclexta.com/previously-un...

"Drink plenty of water during treatment with VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased."

Note that the water drinking requirement of "about 56 ounces total" or about 1.7 litres total, is only when you are at risk of Tumour Lysis Syndrome (TLS) - "starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased." Once the risk of TLS has passed, you can reduce your fluid intake. Also, it's your total fluid intake that is important. While water is best, the requirement is for plenty of fluid to flush unrecylable CLL breakdown products out of your body. The same requirement to drink adequate fluid is equally relevant no matter the treatment. Unfortunately there's decades old misinformation around about caffeinated drinks requiring the additional equivalent in water to counteract the slight fluid retention properties of caffeine. I'm sorry that misinformation on fluid consumption put you off a very good drug.

Neil

[AussieNeil Partner Administrator]

Adding to your post Bob, we now have the choice of acalabrutinib in a growing number of countries and in the US, zanubrutinib/Brukinsa under off label use per NCCN recommendation. These drugs have been shown to have a lower risk of atrial fibrillation developing with long term use, but the risk is still high enough for anyone who sees a cardiologist to have their risk of developing afib reviewed by their cardiologist before starting treatment with acalabrutinib or zanubrutinib. The only advantage ibrutinib has is that you only need to take it once per day, rather than twice per day, or if you can only get acalabrutinib, not zanubrutinib where you live, you can adjust your dose. (The ibrutinib dose for CLL is three, 140mg capsules daily, vs two, 100mg capsules (now changing to tablets) daily for acalabrutinib, or 160mg (two 80mg capsules or one 160mg capsule) twice daily for zanubrutinib/Brukinsa, for lymphoma).

Per NCCN Update Moves Zanubrutinib Ahead of Ibrutinib in CLL/SLL Based on Toxicity Profile, as published in the American Journal of Managed Care

ajmc.com/view/recent-nccn-u...

Changes in CLL/SLL without del(17p)/TP53 mutation for first-line therapy include the following:

Ibrutinib was moved from Preferred Regimens to Other Recommended Regimens. A footnote states that the recommendation is based on toxicity profile, and “a baseline assessment of cardiac function should be done prior to initiation of ibrutinib. In patients with no intolerance, ibrutinib can be continued until disease progression.”

Preferred regimens are zanubrutinib, which was moved from category 2A to category 1, and venetoclax with obinutuzumab, which moved from 2A to 1 for patients younger than age 65 years without significant comorbidities.

Regimens removed were chlorambucil, rituximab, and fludarabine with rituximab.

For CLL/SLL without del(17p)/TP53 mutation in second-line and subsequent therapy:

Regimens were reorganized into 2 categories: second-line or third-line therapy and therapy for relapsed/refractory disease after BTK inhibitor or venetoclax-based treatment.

In the first category, ibrutinib was moved from Preferred Regimens to Other Recommended Regimens, with the same footnote as in first-line therapy. It retains a category 1 recommendation.

Existing Preferred Regimens in the first category are the BTK inhibitors zanubrutinib and acalabrutinib (category 1), and the BCL2 inhibitor venetoclax (category 1).

Also in the first category, several combinations were removed, most notably bendamustine, rituximab (BR), plus ibrutinib. However, BR remains an option in the second category.

In the first category, retreatment with venetoclax and obinutuzumab may be useful in certain circumstances.

Under recommendations for CLL/SLL with del(17p)/TP53 mutation:

In first-line therapy and second-line and subsequent therapy, ibrutinib was moved from Preferred Regimens to Other Recommended Regimens, with the same footnote regarding toxicity and cardiac assessment. It retains a category 1 recommendation.

Under Other Recommended Regimens, ibrutinib plus venetoclax was added as a category 2B recommendation.

In second-line and subsequent therapy, ofatumumab was removed.

In first-line therapy, the Preferred Regimens remain acalabrutinib with or without obinutuzumab, venetoclax with obinutuzumab, and zanubrutinib.

In second-line and subsequent therapy, Preferred Regimens are acalabrutinib (category 1), venetoclax plus rituximab (category 1), venetoclax, and zanubrutinib.

NCCN Guidelines for CLL management, Version 3.2022 June 2022

jnccn.org/view/journals/jnc...

This notes in the Management of Adverse Events section

Zanubrutinib was also associated with a substantially lower rate of atrial fibrillation (2.5% vs 10%) compared with ibrutinib in the ALPINE trial, and the rates of major bleeding (3% vs 4%) and treatment discontinuation due to AEs (8% vs 13.0%) were also lower with zanubrutinib.31 In contrast, neutropenia was more frequent with zanubrutinib (28% vs 22% for ibrutinib); however, this did not translate into a higher rate of infection (60% vs 63% for ibrutinib).

Neil