Study shedding more light on how Ibrutinib works

[AdrianUK]

Interesting paper on the mode of action of Ibrutinib and idealisb. This might explain some of the clinical manifestations of treatment, and would support the idea of combining one of these drugs with another drug.

In summary in a culture setting outside the body these researchers showed that the inhibitor drugs didnt actually kill the CLL cells very much. What they did do was inhibit their multiplication.

So, to actually see an elimination of CLL it makes theoretical sense that you may want to combine a drug like Ibrutinib with one that actually kills lymphocytes like say Rituxamab. The idea would be that the two drugs would work synergistically and hopefully in a stronger way. No wonder drug combinations are being investigated in trials like the FLAIR trial (UK only, other combination trials available elsewhere). This makes me feel even more like at least exploring FLAIR when it comes to me needing treatment.

More details here:

ncbi.nlm.nih.gov/pmc/articl...

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[HAIRBEAR_UK Founder Admin]

Remember FLAIR is randomised and the Ibrutinib rituximab versus FCR alone randomisation arm is being phased out, you could also be given single agent Ibrutinib at the moment in the trial's latest incarnation among the others. As an adaptive trial it could be possible ln the future for the FCR randomisation to be phased out and another comparator introduced into FLAIR if IV performs as FCR is routinely available for commissioning as standard of care first line. CLARITY is going for cure in relapsed, FLAIR could one day follow while answering many questions in first line along the way. The challenge will be getting payers to fund them in large populations once trial data matures.

[AdrianUK in reply to HAIRBEAR_UK]

HI I was not aware they are phasing out the I-R arm. They were only going to do that to any arm if it had been shown to not be as effective as the others. Have they shared that information publicly or are you pivvy to some special source of information?

[HAIRBEAR_UK Founder Admin in reply to AdrianUK]

Adrian. FLAIR has an adaptive TAP design which enables the trial to evolve over time as randomization phases complete. This will continue and offers an opportunity to trial newer technologies and combinations against standard of care in this setting. Giving patients and treating doctors ongoing oportunities.

[AdrianUK in reply to HAIRBEAR_UK]

I’m aware of that. What I wasn’t aware of was that they already had results telling them to drop an arm. Seems a bit early for that. And theoretically I’d be very surprised if IR was inferior to I alone. Makes no logical sense unless the side effects are bad. Do you have more information about this? They have only just added a couple of arms. I do think they need to improve their communication. We should consider setting up some Skype calls to grill experts a bit like patient power does and invite the trial folks to do so.

[HAIRBEAR_UK Founder Admin in reply to AdrianUK]

At the moment FLAIR has 4 arms All arms continue to mature data when quotas fill. I think the latest additions are very relevant comparators against standard of care judging by the published results of Ibrutinib plus Venetoclax from CLARITY in the relapsed setting, and the EMA license for single agent Ibrutinib for use in firstline treatment.

In the UK Patient groups have good communication lines with the academic clinical research community and representation on steering committees in the CLL clinical and research community.

[AdrianUK in reply to HAIRBEAR_UK]

That may be true. But those of us who are not in those committees don’t get to hear what’s going on. Which is frustrating. And now I don’t even undetand what you are saying. There are four arms. But earlier you said maybe they were closing one. Is that true? And if so why is the information not shared more broadly. There shouldn’t be information haves and have nots in the patient community. Just one more example of an exclusionary in crowd. How is it in patients interest not to even know what’s going on? We should be kept better informed by our representatives otherwise who are they representing?

[HAIRBEAR_UK Founder Admin in reply to AdrianUK]

Adrian I have tried to explain above the adaptive trial design of FLAIR and where it is. You are very combative vociferous and new to the community I am sure after attending CLLSA and LC meetings you will get to know a little more from talks and updates and get a chance to spend time with other patients Also gain some insights on how volunteers and advocates work to support the community and build on the work of others.

[AdrianUK in reply to HAIRBEAR_UK]

I’m sorry if I come accross as combative. But you clearly said one of the four arms of FLAIR was closing. What you haven’t said is how you know this. And why if this is true this information hasn’t been communicated more broadly. A patient group should communicate important news with their members, and frankly this doesn’t seem to be happening.

If someone is thinking of going into the trial they have a right to know which arms are open currently, and which may close and why.

I have already attended one of the CLLSA conferences. They happen once a year in London. There needs to be better communication in between.

[HAIRBEAR_UK Founder Admin in reply to AdrianUK]

Adrian many people living with CLL work hard and give and have given a lot of their time to help keep us all informed and supported. It is good you have attended a meeting. I hope you found it helpful and informing and empowering and you attend many more and participate and learn with others

As information comes available it is disseminated. Part of why this online community here was created to enable us to support each other and patients to become informed.

The published FLAIR patient information is current and you have the updates

I have tried to make clear where FLAIR is to my knowledge at the moment. The key message initially in my first reply to you was that as a randomised trial there is no guarantee that you will get the combination therapy you seek. But it does give people a chance first line in the UK. As data matures let us hope that novel therapies in the trial themselves become a standard of care option in the future and you have a long watch and Wait until you require treatment.

[Jm954 Administrator in reply to AdrianUK]

If someone is thinking of going into any trial then all their possible treatment options plus possible side effects and investigations etc are explained to them both by the Drs and in the patient information sheet. Remember you can also opt out of a trial at any time even after entry.

I should not be possible for someone to be entered into a trial and then find that an arm has closed. The information about arm closures is widely disseminated to participating centres weeks before the closure with a notice that says something along the lines of that "the arm has almost reached its recruitment target and will be closing on xxxx date so that data analysis can begin". At the point of randomisation it will be clear which arms are open.

[JigFettler Volunteer in reply to HAIRBEAR_UK]

I also heard FCR in future could be phased out... cant recall from whom ...also that as of now the data just is not there yet to support that.

[TimHB]

I'm in a clinical trial at Moores/UCSD in La Jolla California on both ibrutinib (420mg/daily) and 9 infusions of obinutuzumab (Gazyva) over 6 months. Is this the kind of combination you're referring to? They hope for up to 10 years of remission, but that I'll take the ibrutinib for the rest of my life (or until they develop something better).

[AdrianUK in reply to TimHB]

Yes sounds like that’s exactly the kind of combination I’m talking about tho I’m not massively familiar with the specific drug you mention. Basically a drug which actually kills the cells well combined with a drug that stops them multiplying logically would be more effective than either alone...

[Jm954 Administrator in reply to TimHB]

This combination is being considered by NICE in the UK for first line treatment in the near future.

[PaulaS Volunteer in reply to Jm954]

Very interesting, Jm954 , to hear that NICE is considering ibrutinib and obinutuzumab (Gazyva) therapy for first line treatment in the UK.

Sounds great, but I wonder how NHS will respond to this idea, seeing as they are cutting back on prescribing ibrutinib for relapsed patients, who would seem to need it even more than first timers.

Am I missing something here?

[Jm954 Administrator in reply to PaulaS]

No idea Paula, no joined up thinking there!

[RitaBa]

Very helpful.

Thank you Adrian, your posts are always informative and thought provoking.