Interesting article on treatment choices

[Research123]

curetoday.com/cure-tv/what-.... I found this an interesting article on treatment choices. Not sure if it helps in the UK who seem to be behind usa in treatment choices but interesting anyway

[caven]

Ummm ... instead of "the UK who seem to be behind us in treatment choices" I think you mean 'have a different treatment trajectory than in the USA.'

Let's not start another reason for the Brits to keep the doors closed to visits.

Caven

[Research123 in reply to caven]

I was referring to the fact that as I understand it default on nhs starts as chemo unless you can get on a clinical trial

[Hidden in reply to caven]

most of the issue in usa has been with the reopening of bars(pubs). Young people are ignoring most rules. I suspect the same thing will happen in UK if they re-open pubs in july.

[Research123 in reply to caven]

Actually I've adjusted behind us to behind usa (I meant behind US in big letters)...I'm a Brit but think my typo read rather badly so sorry if I unintentionally upset anyone

[AdrianUK]

Actually here in the uk the docs and NICE argue that chemo might still be a good option for many people with CLL because it can effectively cure some people.

17p deletion and TP53 mutations are the two reasons you definitely shouldn’t take chemo and here in the Uk you are offered ibrutinib or venetoclax if that’s your markers.

Where it might be considered controversial is UNmutated IGHV. Since it is true that on average people do less well on chemo if they are unmutated than if they are mutated. But here in the uk outside of a trial (or a special scheme from one of the companies) you do have to try FCR first. If it doesn’t work you can stop it and then get V or I. We can also get V or I second line and then have as much of either as we need for the rest of our lives without ever paying a penny.

So far I am proof that actually FCR can work for some unmutated people. I will have started it two years ago in October and I had a very rapid response and got to MRDU status at less than 1 in 100,000 cells. I’m currently cll drug free and still have a lymphocyte count of less than 1 (thousand) which is a good thing.

So far I’m actually quite glad I got FCR even tho I did enroll into a trial in the hope of getting I plus V but ended up being randomised to FCR.

Ibrutinib may only work for a few years (at this point we sure don’t know if it will last at least a decade or more which is certainly what I’m looking for) so personally I’m kind of glad that I will have banked some years from FCR before needing to start it. At the moment I personally would be leaning more towards the idea of venetoclax plus rituximab as a second treatment for me personally in the hope of getting back to MRDU and having another hopefully nice and long remission. (Though having said that during covid there is a strong argument for using eitther ibrutinib or acalabrutinib but I’m not planning on needing treatment just yet).

It is actually just possible that the wholesale adoption of ibrutinib as the first line treatment for almost everyone with CLL in some clinics in the USA might actually eventually turn out to be a bit of a mistake at least for some younger patients. We do not yet know.

The FLAIR trial should show us whether over ten, twenty years or even longer people do better if first started on FCR or If it is indeed better to start with a newer treatment.

Bear in mind that we only ever do one set of six FCR Cycles here in the uk and there really isn’t any clear data about what is the best option in the really long term yet.

Nobody is saying don’t use I or V the issue is just is it worth delaying the start time on either of those drugs especially if you are young by using FCR that one set of cycles. Or is it better to just start with the newer drugs?

Of course we don’t know the real answer to that question and it maybe that between them venetoclax and Ibrunib in sequence or in combination can hold many people for decades. We just don’t have the data yet.

I do know that whether I need another treatment in one year or in ten years time I won’t have to take FCR again and I can guarantee free acces to my choice of either venetcolax plus Rituximab or ibrutinib or any other treatment thaf is approved and funded by then.

There is a logic to the UK position. It might even turn out to be the correct logic when we have the data. It might not. It is so important to gather real clinical trial data to inform questions of which treatment to use. So clinical trials are important and hundreds of patients in the Uk have entered the FLAIR trial to attempt to get a definitive answer to that question for future generations of CLL patients.

[Research123 in reply to AdrianUK]

Thank you so much for your informative note. I am glad things worked out well for you. I had always assumed that FCR use in uk was just as it was cheaper not that it might be better in some circumstances. I suppose as time goes on we see how things progress which they seem to be doing quite rapidly.

[AussieNeil Partner Administrator in reply to Research123]

About 55% of those with mutated IGHV treated with FCR are seeing indefinite remissions, with those in the first FCR trials now approaching 20 year remissions. If you can make it to 7 years (after just 6 months treatment), the CLL just doesn't come back.

I'm just half way through a very promising non-chemo trial (Acalabrutinib+Obinutuzumab+Venetoclax) and have a further 6 months to go. I hope to get as good or better a remission length on this novel treatment as was likely for me on FCR - IF I could have got through at least 4 cycles. My severe, chronic neutropenia meant I'd probably struggle to achieve more than 1 or 2 FCR cycles. It would be so good to have finished treatment now and be on the way to seeing my immune system recover, rather than having to face another 6+ months with minimal ability to fight off viral infections due to having a low lymphocyte count. However I'm hopeful of a better recovery of my ability to make immunoglobulins after I finish treatment than is typically the case after FCR.

Ironically there's around a 10 to 15% risk of developing high blood pressure or atrial fibrillation on long term Ibrutinib and about a 10% chance of developing AML or MDS on FCR. Any treatment comes with short and long term risks...

Neil

[Research123 in reply to AussieNeil]

Thank you Neil. I hadn't realised treatments could be so effective. I do really appreciate the efforts you put in this forum which help me feel so much better and it would be wonderful for you to be well enough to need no more treatment.

[Jm954 Administrator in reply to Research123]

This is the salient paper on this subject from the UK trial CLL8 which was comparing FC vFCR (Rituximab was new then) and there is an excellent breakdown of outcomes based on a wide variety of prognostic markers.

It's only relevant to look at the FCR arm for outcomes but it's very interesting and informative. FCR is far from finished as a treatment, which is good news for those patients in countries where the new treatments are beyond the reach of the public or patient purse.

ashpublications.org/blood/a...

Thanks for posting, it led to a good discussion.

Jackie

[Research123 in reply to Jm954]

Thank you

[Sushibruno in reply to AussieNeil]

Yes definitely and unfortunately, 🙁.

[cajunjeff in reply to Research123]

I think you had it right in the first place. Whether fcr ultimately turns out to be a better choice than ibrutinib or venetoclax or some combination of the two is a separate issue as one’s right to choose among reasonable treatment options.

I think people in the UK and their doctors should have the option to choose Ibrutinib as a first choice. I think the reason they do not is driven more by economics than science as I believe the consensus opinion among Cll experts worldwide is that ibrutinib is a better frontline choice for most unmutated Cll cases.

I am sensitive to the fact we have members on here from across the globe who have varying degrees of access to different Cll drugs, some people unfortunately with very few options.

But our discussions still need to be science based. Generally speaking, more options is better than fewer options. The UK has a wonderful healthcare system that does a lot of things arguably better than the US. Frontline availability to ibrutinib is not one of them.

I can think of no science based decision not to make Ibrutinib available frontline. I think if you surveyed UK Cll specialists almost every single one would want the option to treat patients with ibrutinib frontline.

Since I can think of no science based decision, I assume it’s an economic decision. That is not to imply that in any national healthcare system, economics should not be a factor. Ibrutinb is way too expensive. My very strong suspicion is that if Ibrutinib was cheaper it would be approved.

Fcr is certainly a reasonable choice for anyone with Cll young enough to take it who is not 17p deleted. That said, I believe it fair to say the Cll expert doctor consensus opinion would be to start someone on ibrutinib if they had unmutated Cll.

I think even those people who are young with mutated Cll who would do great on fcr should have the option to choose a therapy that might work just as well with less risk of toxicity. I could be missing something. Is there any science based reason people should not have the option for immunotherapy over chemotherapy?

[AdrianUK in reply to cajunjeff]

I think I I outlined the science based reason and so did Niel. If you can tolerate FCR it has a chance of being effectively a cure. Ibrutinib seems likely to havd a shelf life eventually for most people which might not need to concern an 80 year old but should be a factor in the thinking of a 40 year old. We do hope that venetoclax containing treatments are going to be as good as FCR or maybe even better in the really long term but there is NO WAY to know that for sure just yet. Not till theyve been around for 20 years or more. It’s easy to assume that a drug works. But despite some poeple being very hopeful about them antimalarial drugs have been clearly shown to be a flop for COVID-19 not least by a huge scientific randomised control trial run by the Brits (the rest of the world can thank us for that as well as flair). Meanwhile the humble drug dexamethasone has been shown by the same trial to actuAlly save lives in those needing ventilation or oxygen. Clinical research gives us facts for support or disprove the hope. For now for outcomes longer than a few years FCR is the only treatment with real scientific data and not just hope.

[cajunjeff in reply to AdrianUK]

You are misreading my post and making it political when it’s not meant that way. And it’s also incorrect to state that for outcomes longer than a few years that fcr is the only proven drug.

I tried very hard not to make this a US vs UK issue as you have done by bringing Trump into the discussion.

The sole issue I was addressing is that there is no science based decision for people in the UK not to have access to ibrutinib as well as fcr for frontline treatment. As I clearly stated, fcr is a proven and acceptable treatment for mutated and unmutated Cll. But so is ibrutinib and for unmutated people with Cll, on average, ibrutinib gives superior results with less toxicity.

My only point was that I think people everywhere, not just the US and the UK, should have at least the option to make a non chemo treatment choice.

Is that even a controversial thing to say? Wouldn’t every Cll doctor in the UK want ibrutinib in their front line arsenal?

Adrian, surely you do not think for outcomes less than a few years, fcr is the only proven drug. That’s not even close to being correct. There are tons of data on ibrutinib and emerging data it outperforms fcr for some risk groups.

I am disappointed you turned this into a US vs UK thing. I acknowledged there are many things the NHS do better than the US system.

Of course there is science supporting the use of fcr. My point is that there is no science based reason not to also have Ibrutinib as an alternative. How is that even controversial?

Is it your argument that people starting treatment in the UK for Cll should not have the option for ibrutinib and or venetoclax?

Fcr is still an excellent treatment option and the fact it is time limited therapy gives it an advantage over Ibrutinib. Fcr is clearly an appropriate choice for most people. Ibrutinib has its advantages as well and I suspect many join the Flair trial as the only way to get Ibrutinib. Ibrutinib is an appropriate option too, and to suggest there is no science or data to support that seems disingenuous to me.

onclive.com/view/ibrutinib-...

[PaulaS Volunteer in reply to cajunjeff]

Jeff, from what I have heard, doctors in the UK do have the option of prescribing Ibrutinib for first line treatment. But it would have to be a private thing as the NHS does not fund it for first treatments (except for those with 17p deletions). If people have private insurance or the funds to pay, then it would be an option for them.

I also think older people who are too frail for FCR, might get Ibrutinib funded by the NHS. I'm not absolutely sure on that, but the rules on these things are constantly changing.

Paula

[cajunjeff in reply to PaulaS]

Paula, the fact that the NHS will not fund ibrutinib frontline but for a few exceptions has the practical effect of making the drug inaccessible for most people. If someone has private insurance that covers Ibrutinib or if they can afford to shell out 150k a year, they would have access.

I suspect the reason the NHS doesn’t cover ibrutinib is more a financial based decision than a decision based on the science as most all Cll doctors think ibrutinib is a good drug for those want to take it front line. I am passing no judgment on the NHS, I imagine they have a budget and have to make a lot of tough calls.

[Jonquiljo in reply to cajunjeff]

I 100% agree! The only thing I might add is that FCR is generally not recommended for patients over 65 - though the average age of a CLL patient on diagnosis is 71 years old!

CLL is a complex disease ... which is why there are CLL “experts.”

[AdrianUK in reply to cajunjeff]

All I am saying is that we do not yet have clinical data that demonstrates any of the new drugs can get you to 20 years without switching. I totally agree it is highly likely Venetoclax containing combinations will be able to do that for some people. And that if you use ibrutinib and venetoclax in sequence or combination it’s likely that between the two of them they will do that. But the data is not there. So it is possible to argue that FCR is a reasonable thing to try first. And I don’t think we should be discounting it as an option at the moment especially not for those with good markers. I think if I had been 13q Mutated I would almost certainly have chosen that at the time I was treated over ibrutinib. And I think I still would although the latest data on venetoclax plus obinituzimab would tempt me much more than starting a drug you have to take long term when you are in your 40s. With being UNmutated the data is less clear but as I say it seems to have worked fine for me. That’s a personal view and I fully accept that iBrutinib is a reasonable firstline Choice for some patients. I think that we were talking at cross purposes as the impression I had was that you were saying there was no scientific justification for a decision to take FCR first line. We also have a diffeent philosophy over here where we tend to have clearer treatment pathways rather than simply allowing patient choice. And for now NICE and our experts have recommended FCR first line though that might change soon. Venetoclax or ibrutinib are both available second line and you certainly wouldn’ have to complete a full set of FCR if it wasn’t working for you. For me it was so obviously working after the first cycle so continuing it seemed very sensible.

[Justasheet1 in reply to AdrianUK]

Adrian,

That was not your best post by far. I wish you could have just stuck to the topic.

Given what you understand about the drugs, what would you choose, given the choice, as your first therapy if you were unmutated as I believe you are?

Jeff

[Jm954 Administrator in reply to Justasheet1]

From adrian's reply earlier in the thread

"So far I’m actually quite glad I got FCR even tho I did enroll into a trial in the hope of getting I plus V but ended up being randomised to FCR. "

[Aklambert in reply to AdrianUK]

FCR ended up being the correct choice for me (on FLAIR) four years ago, at least while they sort out the side effects of I and V. 2.5 years ago, my immunologist told me - as he was discharging me from his care with immunity back to normal levels - that FCR was the best choice, for me, for a normal life going forwards. I didn't evening get a shielding letter (I would have ignored it anyway). 68, back to work and back to full triathlon training - except swimming

[Research123 in reply to Aklambert]

Glad to hear how well you're doing...I'm 16 years younger and doubt I could manage a1/8th of a triathlon.....

[Hidden in reply to Research123]

i could handle 1st one to the refrigerator=lol