Update for UK FLAIR Study Participants who have come to the end of 6 years of Ibrutininb treatment.

[Jm954]

Many patients were fortunate to receive Ibrutinib as their first treatment in the UK FLAIR study and the first patients are now at 6 years of treatment. These early patients have been told that their treatment will now stop and they are rightly concerned that they will lose their deep remissions and start to progress, many have expressed their concerns on this site.

We now have clarity regarding future treatment for patients whose Ibrutitnib treatment will be ending with this statement (dated 4th Feb 2021) which is from Dr Prof Peter Hillmen who is the doctor in charge of the FLAIR study.

"FLAIR and STATIC trial update

Background: The development of ibrutinib has had a major positive impact for patients with chronic lymphocytic leukaemia (CLL). However the “life-long” use of such drugs can create some problems, such as the emergence of side effects over time and the risk that the CLL develops resistance to ibrutinib. Continuous ibrutinib may not be the best approach and there is evidence to suggest it might be better to give drugs such as ibrutinib intermittently. It is known that when patients with CLL stop ibrutinib for toxicity it is an average of just under 2 years before they progress. “Intermittent” ibrutinib use means that once a patient is in a good remission there is a pause in treatment, which might last for some considerable time, until there are early signs of CLL reappearing (before the patient has any symptoms). At this point ibrutinib would be re-started until the patient was back in remission. Intermittent treatment has the potential to reduce side effects as well as reducing resistance to therapy.

FLAIR Trial: The FLAIR Trial is the current UK trial for patients with CLL needing treatment for the first time. In FLAIR patients are scheduled to stop ibrutinib after 6 years by which time they should be in deep remissions so that we might anticipate a long time before progression.

STATIC Trial is designed to answer the question whether continuous ibrutinib until CLL progression or intermittent treatment with ibrutinib is better. Patients receiving ibrutinib in FLAIR will be eligible to enter STATIC. These patients coming from FLAIR who have been taking ibrutinib for 6 years will have the option of any of the following:

1) Enter STATIC and be randomised to continuous ibrutinib or intermittent ibrutinib (note this is not stopping ibrutinib permanently but pausing ibrutinib - patients will re-start in STATIC at the first sign of their CLL reappearing)

2) Enter STATIC and elect to stay on ibrutinib continuously (individual patient choice)

3) Not enter STATIC and remain off ibrutinib in follow-up in FLAIR (the patient will still remain under regular follow-up with their trials team)

It is hoped that patients would mostly be randomised in STATIC between continuous or intermittent ibrutinib. Patients in STATIC will be closely monitored to make sure that we identify if there are any group of patients who progress quickly after pausing ibrutinib so that such patients are not subsequently entered into STATIC.

Previously treated patients with CLL in STATIC:

In addition to patients from FLAIR (“previously untreated patients”) STATIC will also be open for patients with previously treated CLL who are in a good remission on ibrutinib. These “previously treated” patients will be able to enter STATIC without previously being in FLAIR.

When will STATIC open? Under ordinary circumstances it would take about 9 months to open a trial like STATIC - there is a lot of work to do! Therefore it is unlikely that STATIC will open before September 2021 (although we are trying to expedite this). This means that patients entering FLAIR before September 2015 will have come off ibrutinib before STATIC is open. These patients will pause ibrutinib after 6 years but will be offered entry into STATIC when it is open having the same choices - either be randomised or elect to continue (in this case re-start) ibrutinib. The only exception is that if any of these patients have signs of returning CLL then they will be able to elect to continue ibrutinib in STATIC but will not be randomised

I think this is a very reassuring statement and hope it helps to allay any fears and worries. Hospital consultants should have this information very soon, if not already, so please discuss with your doctor if you wish.

Jackie

[annmcgowan]

Hi Jacky thank you so much for this information. It is very reassuring. I will not stop ibrutinib until 2024 but was a little anxious about the future nevertheless. This is great news for all on ibrutinib especially those entering their 6th year.Ann

[fapumpkin]

Thank you so much for posting this update on the situation as the change in previous advice has caused me great concern and I do not have a haematology appointment until mid March to find out what would be happening if I get to 6 years on the Ibrutinib arm of Flair, in June 2022.

One thing that I am still a little confused about is - if you are coming from the ibrutinib arm of the Flair trial, after September 2021, can you choose to stay I ibrutinib or is it randomised?

[Jm954 Administrator in reply to fapumpkin]

As it says, when FLAIR finishes for you, you can enter the new trial and choose to stay on Ibrutinib as an option within the trial if you wish. If you decline the trial then you will come off Ibrutinib at the end of the 6 years.

[fapumpkin in reply to Jm954]

That’s such great news- made my day/week/month 😀👍🏼

[gardening-girl]

Jackie, I'm not in the FLAIR trial and am not eligible for STATIC, but I definitely appreciate knowing about these trials and learning from them. Thank you so much for this post.

[cartwheels]

I'm not on the trial but coming up to 4 years on inbrutinib first treatment still in remission and I can see the benefits of the idea to stop , pause treatment before the patient becomes resistant it could lead to a indefinite time on inbrutinib still leaving other options if needed Dr Hillman is well respected and I would trust his judgement .Of course everyone is different and I can see why some might find this worrying

[Jm954 Administrator in reply to cartwheels]

You would be eligible for the STATIC trial if you are still in a good remission when it starts, you won't have to need to have had 6 years of treatment.

[cartwheels in reply to Jm954]

Interesting I might discuss this with my consultant I seem to recall you are on inbrutinib Jackie and of course you have worked in the health system what are your personal thoughts on this

[Jm954 Administrator in reply to cartwheels]

@cartwheels, I've been involved in this development in a minor role, providing some input to the STATIC group and obtaining this statement from Prof Hillmen and I am now happy with this trial.

It offers the best of both worlds, to be able to continue on Ibrutinib as patient choice or the randomisation of interrupting treatment v continuation. My worry was that patients would have to have a frank relapse before treatment would be reinstated but that is not the case, at the first signs of relapse treatment will be restarted and patients are expected to respond.

In the STATIC trial patients will continue to be monitored and, although I haven't seen the full protocol, I expect that to include MRD monitoring as happens in FLAIR at 6 monthly intervals.

I will have had 6 years on Ibrutinib in October and was concerned about stopping as I've done well but Ibrutinib hasn't been without side effects for me, including significant hypertension.

I'm doing some serious research into the side effects of long term Ibrutinib, especially cardiovascular risks. There is some data coming through and I'll try to keep up to date with it. That data will inform my decision about which arm of STATIC to opt for when the time comes, bearing in mind that I have already developed HT. I'm also working on a major project - me! Trying to lose more weight and improve my fitness levels with a target of walking 5 miles each day in order to help my cardiovascular system.

Every day is a bonus and I'm grateful for it. Had my vaccination today too!

Take care,

Jackie

[mrsjsmith in reply to Jm954]

Good news re the jab Jackie,

And if I was on the FLAIR trial I would be very grateful for all your imput.

Colette x

[cartwheels in reply to Jm954]

Thank you Jackie I am certainly interested my side effects are not to bad mainly muscle and lower back pain consultant had never been concerned maybe send me a link to inquire about static .Had my jab yesterday and I feel like I have been run over by a bus terrible night hot ,body aches , confusion but better today but feel weak at least I have had a reaction 🤣

All the best

[Jm954 Administrator in reply to cartwheels]

STATIC is still in early planning and we’ll post here when it’s open for recruitment. It should be circulated to all consultant haematologists so that they can enter their patients. I had my jab yesterday and feel awful today, same side effects as you. I thought a long walk would help but it didn’t so I’m now on the sofa catching up on films I’ve recorded.

All the best

[cartwheels in reply to Jm954]

Thanks same here bit better but definitely a pj and sofa day hopefully are reaction is a good sign

[NooNoo14 in reply to Jm954]

Rest and take Paracetamol Jackie. My side effects only lasted a couple of days. Interestingly enough, my heart rate went quite low during that time!!!

Netty

[NooNoo14 in reply to Jm954]

Next month I will have been on Ibrutinib for 3 years. As you know, I have AFib which is now permanent since starting Ibrutinib. Like you Jackie, I worry about any long term effects on my heart. Will be interested to hear your decision after the data is issued.

Netty

[Newdawn Administrator]

Thanks for clarifying this issue Jackie, it’s clearly a serious issue for many (including yourself) looking at the previous posts.

I’m glad the information is now public because I found it difficult to reassure people on the previous post apart from being able to say they wouldn’t be abandoned 😉

Newdawn

[pkguk2 Partner CLL Support Association]

Thanks for this, Jackie, and thanks also for all your work behind the scenes to help get this statement approved and published. After all the concern, it's an excellent result.

[Bikerambler]

Thanks so much for this Flair trial update. I'll reach six years on Ibrutinib in Summer 2022, so the news about the Static trial is great. Thank you to Prof Hillmen and his team at Leeds University who are masterminding these trials. I count myself very lucky to be receiving this effective treatment, so far without unacceptable side effects. BW to all.

[Beattiem-UK]

Thanks Jackie. It's very reassuring to know that there are options for future treatment being trialled for those of us currently doing well on Ibrutinib outside of FLAIR. And it's so clearly written.

[KrisBren01]

Thank you so much for the information I have just come off the Flair trial after 6 years, was worried about it but this as put my mind at ease. It's good to be in this group as you all give good solid information and I for one am so grateful... Stay Safe everyone and Big Hugs to all xx

[gogscll]

Thank you so much Jackie. I really appreciate this update. I posted the other day about my dad who will be stopping Ibrutinib in FLAIR is a few days. It is reassuring to know that there is a plan in place for him and others. One thing that wasn’t clear to me from the statement (although I may be not be interpreting it correctly!) is what would happen if a patient who has come to the end of their treatment has signs of returning CLL before the STATIC trial opens? Will they have access to Ibrutinib if needed before September 2021? Thank you so much again.

[Jm954 Administrator in reply to gogscll]

Most patients who stop ibrutinib because of intolerance (rather than progression) when they are in remission have an average of just under 2 years before they progress, so if your dad is in a good remission it is unlikely that he will progress before STATIC opens and will be able to enter. However, if he does progress, then he will not be able to enter the trial and the next treatment will a discussion between your dad and his doctor. Fortunately we have several alternative targeted treatments available and your dad should never have chemo.

[gogscll in reply to Jm954]

Thank you so much xx

[LeoPa]

Very informative, thanks. Those are enviable terms. Let's hope intermittent Ibrutinib will be very successful.