Switch ibrutinib to zanubrutinib

[groggygarbad]

Is there any problem switching from ibrutinib to zanubrutinib?

Why wouldn't that be a good idea?

[SofiaDeo]

I'm afraid I don't understand the question. If one is getting drug treatment (for any reason) and there is compelling reason to stop using that particular med (for whatever reasons), one switches if one can. If there are several options to choose, one does a risk-benefit analysis, weighing the pros & cons of the choices, and selects something. There are pros and cons for virtually every drug treatment, no matter the choice.

[groggygarbad in reply to SofiaDeo]

I'm trying to discover any adverse side effects from people who have switched from ibrutinib to zanubrutinib. I had been on zanubrutinib for four days before catching Covid. More than a month later my doctor started me back on inhibitor but this time on ibrutinib which is giving me some nausea and much fatigue, although my lab numbers are good. He is hesitant to have me back on zanubrutinib and I am not sure why.

[Skyshark]

Both are covalent BTKi drugs.

Ibrutinib is first generation BTKi. It has a wider range of off target interactions that can cause side effects. Some people have been very happy on Ibrutinib for over 7 years. If it's working and tolerated there is no reason to change.

Zanubrutinib is the latest 2nd generation BTKi drug to be approved for marketing. It is considered to be more effective than Ibrutinib. It has a narrower range of off target interactions, so fewer side effects. If available this is now first choice BTKi for long duration monotherapy.

Acalabrutinib is another 2nd generation BTKi. It has only been available for a few years but was 1st choice from it's introduction. It has far better targeting than Ibrutinib or Zanubrutinib. It is considered to be slightly less effective than Zanubrutinib.

The usual reason for a switch of BTKi drug is intolerance. The switch is usually to Acalabrutinib as that has least side effects so is better tolerated.

If one covalent BTKi drug ceases to be effective they will all be ineffective. There is a non-covalent BTKi drug Pirtobrutinib, this will continue to work after covalent BTKi drugs have failed. The median duration as a 2nd (or nth) line treatment after failure of covalent BTKi drug is quite short at 16.8 months. There are 1st line and multidrug trials taking place.

[groggygarbad in reply to Skyshark]

My ibrutinib treatment is working well according my lab numbers but it is giving me some nausea and much fatigue. I'm sick of being sick and wonder if there is some way out of this. Should I just "suck it up" and stop whining or am I missing a solution?

[KatieBlue]

My heme/onc mentioned the possibility of switching. The pros are that zanu is thought to be less likely to develop a-fib and other symptoms, and likely to work longer before ceasing to work. And evidently one must switch to zanu before ibrutinib stops working or before developing a-fib.

The downside is that I’ve read of a few here who did not tolerate zanu. And when I asked about going back on ibrutinib in that case— was it possible or would there be any issues going back, would I still do as well again or …? I was told all good questions, but they didn’t know the answers. That in theory there wasn’t anything to prevent me going back on ibrutinib, but they just didn’t know.

Another consideration for me is that it would mean an increase in the amount of labwork for about the first 6 months or so on zanu. With being at high risk for severe covid/death from covid in combination with the abandonment of universal masking in medical settings and the end of public health as we knew it, my personal decision has been to hold off on switching. Also factoring in— I’ve been doing well on ibrutinib. I also was supposed to have discussed switching at greater length with my heme/onc at my May appt, but she had something unexpected come up. Rinse-repeat for my August appt. also.

. .

[groggygarbad in reply to KatieBlue]

Thanks. I'd be interested in hearing what concerns your heme/onc eventually expresses.

[KatieBlue in reply to groggygarbad]

It’s right before Christmas— I’m not holding my breath.

[SofiaDeo in reply to KatieBlue]

I am unsure why your doc thinks one *must* switch before the ibrutinib stops working. Or that developing a-fib means you can't use a different drug. I am sure there are a number of people here who have reported switching to another BTK after having problems.

pubmed.ncbi.nlm.nih.gov/324...

"Towards the goal of overcoming ibrutinib resistance, multiple alternative therapeutic agents, including second- and third-generation BTK inhibitors and immunomodulatory drugs, have been discovered and tested in both pre-clinical and clinical settings."

The above sentence indicates a newer BTK is being used after ibrutinib resistence occurs. And regarding the A-fib, I would think a "hold" on meds might be done to see how quickly it resolves. Then one could restart a different med. An episode of drug induced A-fib is not a contraindication to starting another BTKi as far as I have seen in the literature.

[KatieBlue in reply to SofiaDeo]

I can use a different drug, it just can’t be a btk inhibitor.

This is what I was told, and I had a family member on the call with me as well, who also asked questions about this.

I had always been under the impression that a-fib was more of an episodic thing rather than permanent. But I was told it was permanent and would have the same response from any in the btki class. Again, family member has same recollection of what was stated.

[SofiaDeo in reply to KatieBlue]

It can be a temporary drug related thing, which is reversible, or there can be permanent changes to heart tissue (for a variety of reasons) such that the a-fib is permanent/more likely to reoccur. If yours has been deemed be a permanent cardiac change/risk, then avoiding a BTK is prudent at this point in time.

[KatieBlue in reply to SofiaDeo]

I don’t have a-fib or any cardiac issues Just in the discussion whether to switch or not I asked if I didn’t switch now, and either ibrutinib stopped working or I developed a-fib or bleeding )any serious side effect where I would need to stop ibrutinib), then could zanu become an option as a next treatment, and I was told no— in any of the scenarios I outlined. .That it would be too late at that point to use zanu.

I don’t know what more to say. The information about changing to a different BTKi took me a bit by surprise so I didn’t have prepared questions. I can’t tell you more than that.

[SofiaDeo in reply to KatieBlue]

I wonder if your doc is thinking of this recent article which states at this point in time, the 2nd & 3rd generation BTKi's are not automatically "safer". Plus your personal history, family history, etc. All the talk about "off targeted effects" don't make it clear these are test tube effects, not well documented in patients.

Studies are ongoing to determine more about this drug class' cardiotoxicity. Because while I am challenging the statements regarding "must switch before side effects (since not all docs do this)" and "any a-fib will be irreversible", the truth is we just don't really know. So I guess I am more of the type who would accept a doc saying "I am unwilling to prescribe because of X and Y and unknown safety issues" as opposed to saying "it's contraindicated, one can't do it" because there really isn't any data supporting the latter statements.

pubmed.ncbi.nlm.nih.gov/363...

[jimvan]

After successfully taking ibrutinib for five+ years, I switched to Brukinsa (zanubrutinib) in April of this year. I did so in consultation with my health care provider to see if I could shake off the side effect of hypertension brought on by ibrutinib. I also lost 40 pounds of weight over 4 months as part of that effort. Hypertension has been eliminated. My clinical numbers from testing have been very similar on both treatments, but I do seem to have more energy for daily activities on Brukinsa (zanubrutinib). I'd recommend discussion with a CLL specialist regarding your desires in this regard. Best wishes, Jim

[groggygarbad in reply to jimvan]

More energy would be appreciated as well a return to normal blood pressure. The success of your switch gives me hope that it can be done.

[groggygarbad]

Doctor is concerned that zanubrutinib won't cross the blood-brain barrier (CLL showed up in my LP spinal tap). On ibrutinib, I'm suffering extreme fatigue and dizziness. Other than anemia and low platelets , lab results are good.

[SofiaDeo in reply to groggygarbad]

Ahhh, I see. All the BTK's cross the blood-brain barrier to some extent; I am reading more about testing this particular ability in discussions/studies using the ones being developed for MS.

There's data confirming both ibrutinib and zanubrutinib *both* penetrate the blood brain barrier. However, data confirming ibrutinib has demonstrated ability to positive outcomes is available, while zanubrutinib being so new, does not yet have many studies behind it (although researchers are definitely doing them). As of late 2021, a preliminary report indicates zanu likely will turn out to be effective, but with very few patients so far there's no hard data saying it definitely will be effective/better.

pubmed.ncbi.nlm.nih.gov/350...

An early study of a different CNS lymphoma compared 3 BTKi's, and ibrutinib came out ahead of zanu. But this one is in no way statistically significant (only three patients! and labwork involving animals), and there are studies coming out trying to see if zanu turns out to be as effective as other BTK's. The big problem IMO, is that there aren't large numbers of patients involved. With zanu being so new, it's going to take a while until there are numbers to support it being a first line treatment for people with known CNS involvement.

pubmed.ncbi.nlm.nih.gov/351...

This case report indicates zanu works in at least some people with CNS lymphoma:

pubmed.ncbi.nlm.nih.gov/370...

So if you find you can't tolerate the ibrutinib, you need to have a really hard discussion with your doc. I feel for you, I went through months of hell on ibrutinib and because at the time there weren't options like venetoclax for my 17p del variant (and this was treatment #3), I took it longer than I would have liked. You say you are having extreme fatigue/dizziness. Many people report their symptoms lessen after a while on the med, which is why I kept up with it for so long. But I had severe near constant diarrhea and major skin eruptions/infections.

You are reporting fatigue/dizziness, which may or may not be post Covid related.

covid19.nih.gov/covid-19-to...

The Covid complicates things because many people are reporting post infection problems. It my not be the ibrutinib.

If you need a temporary short term disability/FMLA, get it. Monitor your blood pressure & fluid intake, and unless you have kidney problems you can probably enjoy some salty foods to help boost your BP. People here report "adjustment periods" for BTK's. It sounds like you have a good doc, who did some research after the LP came back with CLL in the CNS, so switched you to the one having the most data supporting positive outcomes in CNS disease.

[groggygarbad in reply to SofiaDeo]

Thank you SofiaDeo for the informative links about zanubrutinib and covid. My takeaway now is that I shouldn't try to second-guess my heme/onc because medical advances in this area are progressing so rapidly that there's no way for me to keep up. And I trust that my doctor is staying on top of the subject. Your observation about covid could be spot on because my infection was serious and lasted a lot longer than anyone else I know who got it. So, for now while on ibrutinib, I'll keep taking walks an drink lots of water.

[DriedSeaweed]

The other concern is if you can get it mostly paid for. It isn’t on my insurance formulary so I would have gone the acalabrutinib if it had not been for a clinical trial that gives zanubrutinib to me for free.