Jaypirca?

Anybody have experience with jaypirca drug? Been told from pharmacist that is has lower risk for heart issues/atrial fibrillation than calquence but higher secondary cancer risks. Can anybody verify/share more?

[Ellieoak]

I have been on Jaypirca for 7mo. now, so far no problems with it.

[Spark_Plug]

There are some members who've done well on trial of this. If they saw pirtobrutinib instead of jaypirca they may reply as that was recognizable to me. They'll get around to saying something I'm sure. Meanwhile, I found this link.

Sadly, just about every medical therapy has about the same outcome heart or secondary cancer risk. I guess it's just a choice between which you feel your chances are, but I'm not a doctor, so maybe talk with a cardio and see if they can work around a cancer drug that may cause problems.

fda.gov/drugs/resources-inf...

🙂

[Skyshark]

Jaypirca, Pirtobrutinib, LOXO-305 is a non-covalent BTKi (ncBTKi) only approved as a second line drug for use after relapse on first line covalent BTKi (cBTKi). The median time before progression is 19.6 months but many patients had relapsed on prior cBTKi after an unexpectedly short time. It works after the usual cBTKi drugs have selected mutations but selects it's own mutations that prevents a return to any BTKi drug, Due to it's short median it's mainly seen as a bridge before SCT or CAR-T.

pharmacytimes.com/view/pirt...

The are trials for first line. This will answer two questions. Does it cause mutations in untreated patient without cBTK mutations in the same short timespan that it does in relapsed? Can it give the same long duration on maintenance with medians around ten years as the cBTKi drugs?

The comparator in CLL-313 BR is pretty much useless, as proven by SEQUOIA trial.

ashpublications.org/blood/a...

BRUIN-CLL-313 Pirtobrutinib compared to Ibrutinib for patient with no prior BTKi exposure and up to 30% treatment naive.

ascopubs.org/doi/10.1200/JC...

Unless you have relapsed after two previous treatments including a cBTKi and BCL-2 your pharmacist is crazy (and maybe illegal) to be offering it to you.

biopharmadive.com/news/lill...

[AussieNeil Partner Administrator in reply to Skyshark]

Skyshark,

Just to clarify with respect to your informative reply, regarding pirtobrutinib/Jaypirca "causing mutations" in CLL cells. Unlike the older 'chemo' treatments (BR, FCR, etc.), inhibitor drugs work by inhibiting CLL cell division and blocking the 'stay alive' signalling that CLL cells otherwise receive. BTKi drugs like Jaypirca, do this by inhibiting the Bruton's Tyrosine Kinase (BTK) enzyme in the B Cell Receptor signalling pathway. Without that signalling, CLL cells eventually self destruct as no longer inhibited apoptosis pathways are enabled. So it's not that inhibitor drugs cause mutations, but that CLL cells that develop mutations during cell division which re enable B Cell Receptor signalling due to a mutation in the BTK enzyme preventing the BTKi drug from bonding to the BTK, become dominant due to their selective advantage.

Neil

[Skyshark in reply to AussieNeil]

Edited, changed "causes" to "selects".

[Hidden in reply to Skyshark]

Hey Skyshark. It was the hematologist who recommended jaypirca. Started off on calquence - was on it doing very good until I had atrial fibrillation, after 3 years (atrial diagnosed in emergency last November). Started venetoclax in December - then had a urinary infection that led to bacteremia. Doctor discontinued venetoclax, saying it has and might have caused my infection. So you're saying to not take jaypirca?

[Skyshark in reply to Hidden]

Your question wasn't clear to me, thought the pharmacist was suggesting the switch.

As you have developed a heart condition on Calquence / Acalabrutinib you are now considered intolerant to all covalent BTKi drugs as this is the one that results in least heart problems. Also you have had intolerance to Venetoclax. You fulfil the criteria for Jaypirca.

I think the pharmacist was giving reassurance about your heart condition and does have to warn about secondary cancers.

[Teegolf47]

I have been on Jaypirca since June 2023 and the side effects are almost non existent. It is by far the easiest of my 7 treatments. It has not been around as long as the other covalent BTK inhibitors so there is not a lot of long term data on side effects, but the clinical trial data shows a pretty good adverse event profile.

But it may be tough to get if you haven’t failed the 2 treatments. You could try to get it ‘off-label’ but that would be the insurance companies call if they would pay for it.

Terry

[Skyshark in reply to Teegolf47]

Would that also require a doctor to write a prescription? I don't think a pharmacist can make an off label substitution.

[DaveCll]

I have been on it for 15 months. The only side effect that I have had is occasional blister on my gums. But beside that it has been the best drug for CLL I have taken so far. By the way all cll drugs say possible other cancers. Hope this helps

[CycleWonder]

I’ve been on Pirtobrutinib for 20 months as part of a trial for treatment naive patients. It’s been an easy ride compared to what I’ve read on here by others using other options.

My counts are normal now except perhaps the immunoglobulins. I have been diagnosed with arrhythmia but this likely predated my use of Pirtobrutinib.

All in all, it’s been great.

[thompsonellen2]

On it for 4 months with venetoclax. But as others have said, this is only an option if you have relapsed on other BTKi inhibitors (I've been through 4 others). I feel great but unfortunately, t's a bridge for me to another treatment.