This is my 1st post. I was diagnosed with cll in May 2008 and been on w&w since. In march this year
nodes mainly on left side of neck became more pronounced and spleen increased by 1cm. Had biopsy
on left side under jaw. Went ok but then in Sept became enlarged again and spleen more enlarged too.
I saw Prof Andrew Pettitt at Liverpool Royal yesterday and he has offered me access to the CALiBRe trial taking only Idelalisib. I can only find info on people who have had previous treatments and receive the drug in combination with Rituximab and who also have the 17p deletion. I on the other hand am treatment naive and do not have the 17p deletion. My dilemma is this. Do I take the chance to go
virtually blind into this trial and accept the probability of succumbing to the side effects, diarrhea/colitis,
pneumonia etc and without knowing the long term effects or should I decide to go down the fcr route with a little more knowledge to hand. The trial is only for 40 participants accross the UK over I think a 2 year period which make me wonder that they are suspicious of this drug. I would be very interested to hear from anybody who has any experience themselves or friends/family. I have to decide by tomorrow whether to take part or not and am feeling very nervous about doing so. Any replies welcome.
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kendo1
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Do you really have to decide by tomorrow? Doesn't give you much time to mull things over... Have they given you the 14 pages of blurb about CALiBRe? That was what they gave me when I was considering CALiBRe last August, and it took me some time to read and absorb it properly.
After a lot of thought, I did decide to go on the CALiBRe trial. But my story since then has been complicated... Not terribly positive... I could write reams about the different things to bear in mind, when making such a decision. My posts (at the end) give some idea of how it was for me... But of course everyone is different, and different people have VERY varying experiences with the same drug.
When I was making my decision (a long process that started about a year ago), there was a lot of hype about the new non-chemo treatments. They seemed to be the way of the future, and better than toxic things like FCR or BR (Bendamustine + Rituxamab). So, I wanted to explore all my options, and see if there were any non-chemo trials that I might qualify for. Eventually CALiBRe was offered, so I went for it.
However, since then, I’ve heard (and experienced) more of the drawbacks and side effects of Idelalisib and the other new agents. I’ve also heard more about the way FCR can give very long remissions, especially for those who have good prognostic markers (which I apparently did have, being IGHV mutated and 13q deleted). Looking back, I might have done better with FCR than Idela… But I made my choice with the info I had at the time. No point looking back and thinking “what if…?”
You say you are not 17p deleted but do you know what other deletions/markers you have? Apparently some are more likely to respond well to FCR, and some not so well. (Sorry I can’t remember which ones are which, but I think 11q is not so good). Though there’s still so much to learn about these prognostic factors, and some people with supposedly “bad” prognosic factors do unexpected well (and vice versa).
There are so many unknowns in all this. I’m not sure of exact proportions, but I know you’re aware that a fair number of folk on Idela do develop colitis with time. Or lung problems. Some, like me, get rashes. However, most of these ill effects do stop when the Idela is stopped. Usually no longlasting damage is done. And sometimes after stopping the drug for a while, it can be started again, and the problem does not arise again. I was told that out of all the people who get a rash with Idela, 70% of them will NOT get that rash again, if they have a break from the drug then start it again!
Of course FCR has its drawbacks too.. It can leave lasting damage to some people. I’m sure you’re heard about all that. However, younger people usually cope with FCR much better than older ones. (I don’t know how old you are, but age is certainly a factor).
It’s now approaching my afternoon sleep time, but there’s so much more I could say…
When I started the Idelalisib, it was great. My ENORMOUS spleen shrank DRAMATICALLY and I could eat much better, think more clearly. But about 6 weeks later I started to get a rash… Only a slight one at first, but by 8 weeks it was very bad… The doctors said I should stop the Idela for a short time, and see if the rash went away. After just a few days, the rash had started to ease, but my spleen had ballooned up to its enormous pre-treatment size.. and then it ruptured… Emergency surgery saved my life, but it was a very traumatic experience, that I’ve only just recovered from (7 weeks after surgery now).
I’m told that’s the first time that’s happened to anyone stopping Idela, and there were probably other factors involved (eg my ALC was VERY high and my spleen was VERY large before treatment started. It was 18 cm below the intercostal margin). I should have started treatment earlier really, and not ever let the spleen get so big. Spleens become much more fragile when they enlarge too much. One of my doctors said it would probably been better if they’d reduced my dose of Idela slowly, rather than stopping it all at once.
When Idelalisib is combined with Rituxamab, it’s a different story. I think there’s more data on that. I’m sure there are advantages of having the Rituxamab with it, but possibly some drawbacks as well. They need to do more trials, to find out more…
One thing about being on a trial, is that you get very close attention. I was well looked after. But if you do go for the trial, be very quick to contact your medics as soon as something out of the ordinary happens. (Well I guess that's the same with any treatment).
At the moment, I’ve stopped all treatment (except I have to take Penicillin for the rest of my life, because I have no spleen). The spleen was useful to help my immune system, but it was also a big centre of my disease. Since it’s gone, my bloods have improved. I’ll go back to clinic in 4 weeks time and if the bloods are still stable, I’ll come off the CALiBRe trial and not go back on Idela. But I’m open to the idea of going back on it. I didn’t get any other side effects except the rash, and I might be in the lucky 70% who just get the rash once and it never comes back.
There are always other options if we do have to leave trials. I was told I could always have FCR, or Chlorambucil with a monoclonal antibody, or look for some other trial.
It’s not easy when we face these decisions… There’s often no clear answer as to which way will be best… I’ll be very interested to hear what you decide… and how you get on…
Wishing you well,
Paula
P.S. I’ve been writing this at a time I usually have an afternoon sleep, so apologies for the bleary brain.
P.P.S. Here are some posts about my experiences with Idelalisib.
Hi Paula, thanks for your reply. I will be 58 next May. When I saw my local specialist a month or so ago to discuss treatment I was ready to just get on with FCR. However she said that the treatment was pretty harsh and thought it a good idea to have a word with Prof. Pettitt about the possibility of a trial.
I assumed this to be FLAIR but that is not available to me here at the moment. I am keen to get on withe some treatment now hence the decision tomorrow. Although I think I can take more time if I want, it'll just delay the start a bit more. The only thing is I can't find any stories from people that show real durable promise. It seems inevitable that there will be complications along the way as there will of course be with FCR. From what I can gather if and when the drug is stopped maybe 2,4,6 a year after starting the disease returns rather quickly. At least with FCR you have the drugs for a few days x 6 then stop then see what sort of remission occurs. It's a real poser for me at the moment. One advantage of the trial would be that I would get an in depth look at my particular flavour of the disease e.g. IgVH
etc and could come off whenever I wished. One question maybe for some of the experts on this site is what happens to all the cells that are affected by the drug. I believe they go into the bloodstream where they don't like to be. Then what happens to them? Some sleepless nights ahead I think.
I think you're right about the disease returning quickly when you stop the drug. That certainly happened with me... The drug quickly drew the CLL cells out of the spleen, and they went into the blood, but they went back equally quickly when the Idela was stopped.
My ALC shot up from nearly 300 to 480 in the first week with Idela. (Then went even higher). Having said that, I didn't feel any worse for having a much higher ALC. I felt MUCH better than before treatment.
But it's a big question, re what happens to those blood cells that are affected by the drug and go into the bloodstream... They are supposed to be unhappy there, and will eventually die off. BUT, that seems to take a long time - maybe up to a year. So when I stopped the drug just 2 months after starting it, the cells were still floating around in the blood, ready to reactivate and jump back into the spleen again. Which they did, very quickly, when I stopped the Idela! If I'd had a year of taking the drug, there would have been time for them to die off, so not so many around to re-infect my spleen. Also, if my ALC hadn't been so high to start with, the pressure on my spleen might not have been so bad.
There's a good interview with Dr Jeff Sharman about this sort of stuff. I'll have to try and find it. I think it might have been with Brian Koffman (or was it Patient power interview?)
It's such early days for these drugs really. So much we don't know. New side effects are still being noticed, and as for the longterm affects - there just isn't the data yet...
I hope you don't lose sleep over all this though.
Paula
P.S. Length of remissions are also a key point. I don't think the data is that great for long remissions with Idela. Though it can buy people time till something better is discovered, and may be better for older folk who cannot tolerate FCR. At 57 going on 58 ( if you don't have other co-morbities), you should be about to cope well with FCR (though one can never say for sure). Even at the great age of 67, I was told that FCR was still a reasonable option for me.
P.S. When your local specialist said that FCR would be pretty harsh, was that because of some other health problem you might have? Or just because it's harsh anyway...
Haven't found the interview I was looking for, but this is interesting. cll-nhl.com. Scroll down to the bit called "FCR: The Empire strikes back." But it is American where everyone seems to get FISH tests early on and knows their mutated state.
58 next May. Thinking about investigating the FLAIR trial. There seems to be far more positivity with Ibrutinib v Idelalisib. With Ibru there are a lot more posts, good and not so. But with Ideli I can't find 1 post on here or other sites that give at least some hope of durability. Obviously I could end up on FCR anyway but a few weeks ago I was prepared to go down that route anyway. I'm waiting for some feedback from some question from Hosp tomorrow.
This is the fascinating video interview of Dr Sharman by Dr Koffman, where Dr Sharman mentions the recent discovery that CLL cells going into the blood are exhausted, so researchers' previous studies of them have provided misleading ideas regarding how active CLL cells are. This new discovery is about CLL cells in Watch and Wait but has profound implications for therapy.
In Part 2, Dr. Sharman points out the impressive data with idelalisib and rituximab in the most difficult to treat patient population with deletion 17p and he discusses what trials and research is ahead of us.
Neither Ibrutinib or Idelalisib provide durable responses - they are both maintenance drugs that patients need to stay on indefinitely. We are still waiting for researchers to come up with a combination treatment with these that provides durable responses - perhaps even a cure.
Hi Neil, thanks for the link it is very informative. I have spoken to the trial co-ordinator today who has worked on CALiBRe and FLAIR and she said that she is really sorry that they no longer participate in FLAIR. She agreed that it is much better to look at all the options available and is happy to try to get me a referral to another relatively near location to be considered for that trial. Obviously I could end up on the FCR arm but up until a couple of months ago I was prepared to start that anyway. She had the results of my FISH test which showed negative for 11p and 13q. Not too sure how many other results that test gives. So maybe I should just take a little extra time for now. I should know early next week on the referral. Just for the record what are the most important figures I should be looking for.
Hi Paula, I don't have any other major health problems. Only the usual aches and pains that come at this time of life. I work for myself although I'm getting a bit fed up of having to explain to customers about the noticeable swellings in my neck so tending to do less and less which is frustrating. I haven't experienced any night sweats or real weight loss and am fairly active.
I don't have all the blood numbers but local specialist says are pretty stable. My platelets hover around average 112 I think. White blood cells 65 if that means anything. I've tried writing down the figures but they seem to be in different format sometimes. I'll try better on the next visit.
If your bloods are stable, with platelets over 100, WBC around 65, and no other symptoms apart from the the swollen nodes in your neck, then it doesn't look as if treatment is too urgent at the moment. I presume you're not anaemic so that's not an issue (or I think your doctor would have told you). It would be helpful to get copies of your blood tests over the last year, and look at the trends. It's great that you're not losing weight. Shows that your spleen can't be pressing too much on your stomach.
I realise you want to get rid of those noticeable neck swellings as soon as possible, but seeing your present undecided state, I'd be tempted to say "Give yourself a bit more time to think things through".
At your next clinic visit, I would ask a lot more questions. Find out about ALL your options. As you say, there's been more experience with Ibrutinib than Idelalisib, and the FLAIR trial (50% chance of getting R-Ibrutinib) is a possibility, though you may have to travel somewhere else to get it. There are people on this site with experience of FLAIR. And Chris has mentioned some other possibilities that are gentler than FCR... eg FR, bendamustine/rituxan, and Gazyva (obinutuzumab) with chlorambucil. All of those are available in the UK. They have all been offered to me (though I am over 65 and sometimes the criteria for getting certain drugs varies with age). There are also other trials going on in the UK, though they may not be near your home.
On the other hand, it can be overwhelming to have too many options. A few weeks ago you were prepared to go for FCR, and that is still the gold standard tried and tested treatment - especially for younger fitter people like you.
And although it doesn't look as if you need treatment urgently, you don't want to put it off too long. That was one of my problems. I kept waiting for certain trials to open, that kept getting delayed. And all the time my spleen was growing bigger and bigger, and I was getting thinner and thinner...
I hope your time at the hospital tomorrow makes things clearer. We'll be very interested to hear how you get on...
Hi Paula, thank. I am trying for a referral for FLAIR but won't know till next week. So here's hoping. By the way I don't know if you get to see my replies to other posters. If you do you'll see some more info. Hope I'm not going on too much.
I'm glad you've got a bit more time Ken, to gather information and think things through. As Tricia has said, this is probably the most important CLL decision you'll make.
Yes, I can see your replies to other posters (though I wouldn't always notice them unless I actively look for them - which I have now done ).
The decision on your first treatment is probably the most important one that you take. If you really want to make a choice yourself then you would need to understand all of your blood results, plot the trends, have detailed knowledge of your prognostic markers and assess your B symptoms accurately. Otherwise you are taking the decision in the dark. For each drug option there is more work involved in understanding the drug action, short and long term effects and potential adverse effects and how they would be managed. It is also important to know what the subsequent treatments could be as the majority of patients will relapse from current therapies at some stage.
It is vital that you take an informed decision or that you can trust your clinician to explain his recommendation to you.
There are lots of people on here who will help you to understand the data. But if in doubt, always ASK.
Sending very best wishes as you work through this. We are fortunate that we usually have the time to try and get it right.
Hi Tricia, yes you are right that one should explore all avenues. As for symptoms It's coming up to 8 years since diagnosis and to this day have had no night sweats, fevers or significant weight loss. I have enlarged nodes and tonsils mainly on left side. Some smaller one under arms and spleen just about to the top of my stomach. Nothing further down. I am hoping to get a referral for FLAIR but won't know till next week. I have just spoken to my local consultant and she says there is no immediate rush so let's see what the next few weeks bring. I will try to get up to speed on numbers regarding blood. I did find out this morning from the trial co-ordinator that the FISH test did show 11P and 13q as ok. Which I gather is a good thing. Fingers crossed.
There is an abstract from ASH 2015 by Jennifer Brown at Dana Farber about Idelalisib combined with Ofatumumab. Sorry I don't have a link to post, but if you search the abstracts by author you will find it. It is a small study (21 patients) but the bottom line to appears to be (at least to a layman) that there has been more toxicity than was expected.
I didn't mention in my previous post, but this is a trial of Idelalisib as a frontline treatment. Also, although the trial combines Idelalisib with Ofatumumab, for the first two months, the protocol calls for just Idelalisib. This is relevant, because I believe many of the adverse events occurred during those first two months.
From the Results section of the abstract:
"Results: After a median follow-up of 8.1 months (range 0.7-10.8 months), sixteen subjects (76%) had experienced a grade 3 or higher toxicity. The most frequent grade ≥3 adverse events were transaminitis (n=12, 57%), enterocolitis (n=3, 14%), and pneumonitis (n=2, 10%). The subjects who experienced grade ≥3 toxicities, or who experienced multiple toxicities of at least grade 2 (n=13), were younger (median age 65 vs. 75 years, p=0.047) and had higher absolute lymphocyte counts (median 71466 vs. 19250 cells/µL, p=0.017) compared to subjects who experience no or low grade toxicity (n=7). The median time to onset of transaminase elevation was 28 days (range 14-274 days), with most occurring between days 20-30.... "
Here I have cut and pasted the conclusions from the abstract, in case the link does not work:
Conclusions: The use of idela as first-line therapy in CLL results in more frequent and severe toxicities than its use in the R/R setting. Multiple lines of evidence suggest that this toxicity is immune-mediated: the delayed time to onset, an immune cell infiltrate in biopsies of affected organs, and abatement of toxicity with immunosuppressants. Affected patients had depressed Treg functionality at baseline and lost markers of Treg activation after idela therapy, suggesting that they may be particularly sensitive to PI3Kδ blockade and Treg inhibition. In addition to elucidating the mechanisms of idelalisib, these studies will hopefully allow us to better screen and select patients in whom idela therapy will be well tolerated.
I don't mean to scare you away from Idelalisib. I am participating in this trial and so far have avoided the above adverse events. Further, the trial is very small to date (21 patients) and so the results must be considered in that light. However, I thought the abstractb sounded relevant to the choice you are facing and is probably worth discussing with your Drs. Best of luck with your decision and treatment if needed.
John, that is so helpful and kind of you to take the trouble. At the initial meeting with the specialist I was a bit to keen to jump on board. But I had the feeling a bit later on when I had time to digest a). what he said about possible side effects and b). using this site and the amazing people who are willing to tell us of their experiences about the many faces of this disease that it's going to take careful consideration.
You are right about the data, but there are no plans to approve this combination in the UK. Idelalisib plus Rituximab is approved by NICE for R/R CLL patients and treatment-naive 17p- patients (but you need to read the detail). I am on treatment for the latter condition with Idelalisib/Rituximab and I have been very fortunate with my experience to date. I'm always aware that things can change but there was no other treatment available in the UK for my 17p- disease at the time. So I'm happy with my lot!
You have been given a lot of information here on this post, all good. My only question is why on a trial? Are none of the treatments being offered outside of a trial? Or is it because it was offered to you, is this why you considering this route. Also how many ct scans etc would you need on the Flair trial if you got on it.
Tricia makes some really good points about knowing yourself and your body etc. It is
Important to keep a record of everything that you can. So that you know and it will help you to make informed choices with help or on your own.
I wish you all the best with the decision making. Have a good Christmas and all the best for 2016.
Hi Sue, I don't know if you are in the UK but a trial is the only way I could get access to the newer type of drugs. I really have only 2 trial options, CALiBRe or FLAIR. After that it's good old FCR. I'm not knocking it at all as it can give some great results. It's only relatively lately that we are finding out that certain treatments suit certain people. I have been offered CALiBRe but I'm going to explore FLAIR aswell. I'm not sure about FLAIR but I imagine it would be the same as CALiBRe. 4 Bone marrows and possibly up to 4 CT scans in 1 year which is a consideration.
Thanks for the reply Ken. I forgot you are treatment naive and apart from trials this is the only way to access the newer drugs. I am in the UK. There is still a 50% chance of getting FCR on the Flair trial, but I am sure you know this. I must admit it's very hard to make a decision. Get all the knowledge you can on everything before deciding, which I'm sure you will.
Each trial has very specific and different testing... you need to read the trial requirements... some go for an extended period, like a couple of years...
I would contact the trial for detailed protocol..but this will start you off
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Pain in the spleen/splenomegaly
Does anyone has enlarged liver on acalabrutinib?
New Clinical Trial of Ibrutinib + Venetoclax for people relapsing on Ibrutinib 
