SKIP VENETOCLAX, GO TO ACALABRUTINIB

[cll2013]

My CLL specialist said when I need treatment again (had to quit Ibrutinib after 3 years due to afib), he would probably start me on Acalabrutinib. My oncologist/hematologist indicated the treatment would be Venetoclax. I see the specialist on a consultation basis. Anyone face this situation?

[PlanetaryKim]

My understanding is that if you have to quit ibrutnib because you develop resistance (not your case), then you need to go to venetoclax next because acalabrutinib would not work any better on the ibrutinib-resistant patient since both are BTK inhibitors.

But if you have to quit ibrutinib due to side effects (your case here), then acalabrutnib could be a good next treatment - especially if the problem with ibrutinib was cardiac toxicity (afib).

It may come down to which drug is available to you where you live. Here in BC, venetoclax would be made available to me (on compassionate access basis) if ibrutinib stops working or I develop afib. But acalabrutnib is not yet available to anyone in BC. Or so I have been told by my CLL specialist. But everything changing so rapidly now that acalabrutinib has been approved by FDA.

[Canuck901 in reply to PlanetaryKim]

The orbis project was a partnership between US , Australia and CanAda and acalabrutnib was approved in US and Australia surprised it’s not in approved in Canada yet

[PlanetaryKim in reply to Canuck901]

It is possible Health Canada has approved it but it hasn't yet been added province-by-province to the formulary for each province. That can take a while.

[Canuck901 in reply to PlanetaryKim]

No, it hasn’t been approved for CLL in Canada yet , only for MCL. Anyhow I hope health Canada approves it soon , it’s ridiculous it’s not approved here yet with the collaboration done with the Orbis project

[AussieNeil Administrator in reply to PlanetaryKim]

Some second generation BTK inhibitors have different mechanisms for inhibiting BTK than Ibrutinib, which is highlighted in their marketing material. Also there are cases where patients who have developed intolerance to Ibrutinib have been switched to Acalabrutinib and done well.

See Targeting BTK in CLL: Beyond Ibrutinib.

ncbi.nlm.nih.gov/m/pubmed/3...

Neil

[PlanetaryKim in reply to AussieNeil]

Interesting. Did not know some ibrutinib-resistant patients can succeed on acalabrutnib. Good to know!

[AussieNeil Administrator in reply to PlanetaryKim]

There are two separate issues; intolerance and resistance. Those intolerant of the Ibrutinib side effects can do well on Acalabrutinib, but those who have developed resistance would I expected, need to be switched to a BTK inhibitor with a different target or something like Idelalisib or Venetoclax, etc.

[PlanetaryKim in reply to AussieNeil]

Yes - that was basically my point. Next treatment step depends on whether a person is quitting ibrutinib due to intolerance or due to resistance.

[AdrianUK]

There is a common view among skilful doctors that’s broader than just our condition or this situation. Put non technically this could be phrased “if it ain’t broke don’t fix it”. But how this would apply to your situation is that the argument would be formed that you have two main options when you need treatment. One to start what is essentially a highly similar drug to one that we know has worked for you. The chances surely have to be high that this new drug would also work for you and the side effects will hopefully be less. Whereas we don’t know yet for sure how you’d respond to venetoclax. Now of course you could argue in the contrary that Venetoclax works really well for most people, and anyway how can we know for sure Acalabrutinib won’t have the same side effect in you?

It’s all about the best predictor of the future being the past.

Now of course for someone about to start out on treatment who’ve not had anything yet there would be no history to guide and so perhaps venetoclax might be at least as attractive or maybe more is depending on what you think if it’s data.

Truth be told right now NOBODY can tell you for sure whether acalabrutinib or venetoclax is going to be the best drug for any individual patient. CLL specialists who have been involved in clinical

Trials will have built up the most experience and so they may well begin to get a hunch or sense of which patients to suggest which strategies to.

But having said that it is always going to be vital that YOU believe in the strategy. And at this point you’d be well within your rights to try and get another CLL specialist (one of the top ones!) to have a look at your case and give you their opinion.

Ultimately the decision will be yours.

And that choice can be agonising.

Which is one reason some of us go for clinical trials so we don’t have to choose or trust a person to choose for us. Let that computer decide to give me FCR. I can’t blame myself or my doctor. And I did pray that I would get the best treatment FOR ME (which might not be the best for the whole group by the way...). And for me at least FCR seems to have worked really well so far! Sorry none of us can tell you what to do but I hope that may help explain the possible place this specialist is coming from tho of course you should ask them to explain why they are recommending you consider what they are recommending.

[Smakwater in reply to AdrianUK]

How right you are!

It's about who gets to decide if it is broke or not, and what it is that is broke.

I've heard it said that it does not matter how fast the bullet goes if it can't hit the same target twice.

What we have with CLL is multiple moving targets, coriolis, and changing weather conditions.

We can only hope these folks get it right.

JM

[cllady01 Former Volunteer]

I notice you are in the U.S. over 75 and have active afib (if I understand your post correctly)

Has your Dr. talked with you about possible Venetoclax+Obinituzumab?

The following is a good article to print and to take to him to share/discuss how you fit into the current possibilities for treatment of elderly CLL patients who have stopped Ibrutinb because of toxicity with ongoing AFIB--and having been on Ibr. for 3 years.

It is long, but is well worth going through to help you in this decision.

haematologica.org/content/1...

[W00dfin in reply to cllady01]

I am 68 and had to stop Ibrutinib a month ago due to afib and poorly controlled BP. My oncologist is offering a choice between Venetoclax OR Obinituzumab if the monthly flow cytometry and other lab work indicates CLL is recurring in the absence of Ibrutinib. He did not mention Acalabrutinib.

[TerrySA]

Hi all, would appreciate the benefit of peoples experience, facts with regard to Ibrutanib @ afib. In brief, was diagnosed CLL Nov 2018, started Ibrutanib May this year. Bloods doing well, no side effects or so I thought. Just been diagnosed with afib today. Haematologist said May have to come off IB. WHat experiences have people had developing afib and having to come off IB, what options, alternatives are there? Thanking you all in anticipation on this subject.

[AussieNeil Administrator in reply to TerrySA]

See

healthunlocked.com/cllsuppo...

[cll2013 in reply to TerrySA]

I took Ib for 3 years. Around the 2nd year, the afib started. It was light at first, meaning I could feel the quick heart beats for a few seconds. Over the next months, it progressed to the point of my feeling afib for 45 minutes. I was finally taken off of Ib. Now 8 months later my blood work is still o.k. and I am not on any med. I will not be able to go back on Ib. When treatment is needed, either Venetoclax or Acalibrutinib will most likely be considered, as indicated by my CLL specialist and my hematologist/oncologist.

[Canuck901 in reply to TerrySA]

Ask for acalabrutnib

[narl in reply to TerrySA]

I had to come off IB because of a fib so I have been off of it over a year they didn't put me on anything else just left me back in watch and wait I had previously been in watch and wait for 14 years with no treatment I was on IB one year. I know that I did have some a fib about 3months after starting it but I already had a ventricular arrhythmia so I just disregarded my heart rate. I didn't realize that was a fib until I bought a Kardia heart monitor, when it said a fib they took me off the IB. My white count just creeps up a little every couple of months it's back to 31,000 now. And my lip count also creeping up. When I went off of it he said it would probably be about five years before I would need something again. But they don't really know they're just guessing

[Toothdoctor]

Hello,

Respectfully might I ask how bad was your A-fib? Regularly or intermittently?

I have been on Ibrutinib for 3 months and have only had A-fib on a few occasions and it settles quickly.

Is there any data that acalabrutinib does not cause A-fib?

My concern with Ibrutinib is that you have to take it for life or until it stops working. My doctor is looking at a protocol for me that only lasts 2 years by adding Venetoclast after 3-4 months of being on Ibrutinib. Then staying on the two medications for the duration of the 2 years...then hopefully go into remission

All comments very appreciated

DLC DDS

Happy healthy holidays!

[AussieNeil Administrator in reply to Toothdoctor]

The trial I am on lists the side effects and their risk incidence for Acalabrutinib, stating less than 1 in 20 incidence of Afib. Given trials can screen for cardiovascular health and refuse on the basis of high blood pressure or an unacceptable ECG, plus we don't have the long term data for Acalabrutinib that we have for Ibrutinib, it is probable that the incidence will be higher when prescribed generally, but less than with Ibrutinib.

Neil

[Toothdoctor in reply to AussieNeil]

Thanks Neil,

Fortunately I don't have high BP and have a normal EKG.

Happy holidays Dean

DLC DDS

[cll2013 in reply to Toothdoctor]

I am lucky not to have high BP either, all the more interesting to deal with afib.

[narl in reply to Toothdoctor]

Does your doctor know it's causing you to have a fib? I'm surprise they're keeping you on it if they know. Acalabrutnib is not supposed to cause a fib.

[oktwigs]

My son just recently tried the Gazya treatment with inclusion of Ventoclax in January. He didn't even make it through the whole infusion without serious and horrifying side effects. The doc said the FCR treatment isn't a choice for him now because he'd probably react the same way. Thankfully he's seeing a few specialists right after Christmas in Seattle and I'm praying that they can point him in the direction of a safe and effective treatment. He's only 38 and it's hard to see him struggling to keep himself upbeat for everyone, while worrying like crazy about his young family.

[cll2013 in reply to oktwigs]

My heart goes out to you, your son, and his family. It's absolutely right to be seeing a CLL specialist now to get turned in the right direction. I sincerely hope the right med approach is found quickly. Hugs.