Any unmutated IGVH fellow CLLers out there ever do FCR as frontline? I ask please for responses to this direct question...not commentary on the topic in general. Thanks!
FCR/UNmutated IGVH: Any unmutated IGVH fellow... - CLL Support
FCR/UNmutated IGVH
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YjbCLL
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Nope. Was told that outcome for unmutated patients doesn't have as good an outcome with FCR, and the new immunotherapies have better potential for us. Experts interviewed at the recent ASH conference spoke to this as well.
Here is my post (below) on it with some info..... I am unmutated. I am waiting for a Imbruvica/Venetoclax trial to open to start treatment. With the latest Imbruvica study data out, I personally would not go FCR first unless I had to. Data is at around 70 months with Ibruvica monotherapy. First line ~90% that tolerate it are still progression free. The relapse/recovery group is at ~40%. With unmutated IGHV you can expect 4-5 year remission with FCR, could be more.... could be less. Then you go on Ibrutinib and have a poorer progression free possibility. You also have the unknown toxicities of FCR down the road.
Ultimately it is up to you, your Doc, and your insurance. This is one area where socialized medicine sucks. Many unmutated are forced to go thru FCR first line due to Ibruvica costs.
healthunlocked.com/cllsuppo...
Nathan
Nathan...that clinical trial is already open at MdAnderson, no?
They are opening one in Nashville soon. I think one is going on at OSU as well.
Nathan...
Your comment about socialized medical systems is broadly untrue... there is a lag in drug approvals often it can run 18 months to 3 years behind FDA, but it is a factor of patient numbers far more than the managed healthcare system...
The reality is....it might not be economically viable for drug companies to bring a drug to a small market such as Canada or Australia... it certainly has been the case in the past...
Nobody is forced to go through FCR, there are alternatives like GC, bendamustine/rituxan [BR], FR etc... first line.
Currently we are working to get Imbruvica (ibrutinib) approved and funded in Canada for first line use... it lags of course... it is a tiny market with probably a slim profit potential...
The drug companies initiate the process.. its not a given...
References...
ccra-acrc.ca/images/Communi...
~chris
I meant chemo, not specifically FCR. I am actually pro socialized medicine. The US system is a mess. I am also basing my statements on what I have seen since my diagnosis 6 months ago. I guess forced is a strong word, as treatment is not mandatory.
I do think if you need treatment soon and you are in one of the off subgroups like unmutated your options for first line treatment are limited. At the same time you don't have to worry about losing your home or retirement like in the States. You can also have a decent job and have $2000 co pay for Ibruvica and have to go the chemo route due to economics.
Just looked at link: Cost effectiveness and cost utility are out the door in the US........
The US system may be a mess, but at least we get drugs approved once they demonstrate efficacy. Given their restricted budget, countries with socialized medicine seem to be much slower and more reluctant to offer these new high-priced targeted drugs.
If the upcoming US administration moves to flow drugs through the testing period faster, supposedly to bring down costs, things could get even messier. I will feel less sure of taking a new drug if it hasn't been allowed to go through a series of clinical trials over time, with the potential to reveal safety issues.
Ibrutinib/Ibruvica $2k? I'd heard it was 15 times that in GBP per annum.
rob
I've read people on this blog site paying as little as 100$ a month...WTF?
I was throwing out a generic number. In the US it boils down to your income and type of insurance. Say a patient makes $100,000 US a year and they have "good" insurance the pays 80%. Imbruvica at $100k to $115k a year, that is still $20k out of pocket (not counting the other medical costs). This patient is probably going to make to much qualify for a subsidy. These patients are stuck in the middle. The low income patient will get grants and subsidies and possible pay nothing. We have friends in this situation with a child with extreme allergies. They are racking up medical debt they pay what they can, but can not afford to let it go to a collection agency.
If this is the case, I will leave ATL and go back to Israel...ibrutinib will be free there soon. Eff that!
Hi,
Yes, I did. I did 6 fcr treatments. I did it along with duvelisib. According to the cll specialists at Dana Farber in Boston FCR is still front line treatment for cll.
Dina
FCR Is still considered front line, but many experts are not recommending it for the unmutated IGHV patients. I think this is a problem with the clinical guideline updates lagging behind current data. I think there is also going to be economic pressure to keep the more expensive drugs are second line.
If you are mutated than FCR is a good option and possibly a "cure." The lectures I have seen I don't believe any patients that made it ten years without progression have relapsed.
Diana are you unmutated and when did you go through FCR?
Yes, and had it from February through August.
As a Dana Farber patient, it would seem fairer to say that specialists at that institution still consider FCR as front-line treatment for those patients who are of an age and level of involvement for whom it looks like the best treatment of the moment. For patients of some profiles, like me, they would consider it the wrong treatment, turning to the new immunotherapies like Ibrutinib, among others. They are all up on the latest research, learning along with everyone else how to tailor treatments for each patient as results and patterns become known.
Yes, I was unmutated and CD 38- by DX in 9/2013! Went on FCR and was MRD neg aftet 3 cycles, also after the sixtht!
Then after 1 1/2 year CLL cells by MRD was 0,1, 6 months later 0,3, six months later 0,1 again and last one in Oct 2016 0,3!
FCR without any problem, only low leucos Since then, I am doing pretty well all counts in best shape also immunsystem
I feel great!!
Best of luck to you
Seoul
For those unmutated IGVH patients who are considering FCR, you might want to listen to Jeff Sharman and others in this Patient Power video: "ASH 2016 Expert Roundtable: What Does Emerging CLL Research Mean for Patients."
Hi, I am also unmutated, did 4 rounds of FCR from 1 Dec 2015 to end Feb 2016 and I'm MRD negative now. FCR is not the choice I wanted to make but there was no other option for me when I needed to start frontline treatment. I worry about a short remission but have to live with that fear and I'm determined to enjoy every minute of my remission. If there had been a clinical trial of ibrutinib available frontline I would have taken it. I hope that the options are there for unmutated patients frontline from here on in internationally.
Here's the twist for me. I was dx as 13q14 MUTATED. Eight years later I was given FCR. l didn't go into remission. A year later l was tested FISH no mention of my mutation status. Then given ibrutinib I took it two months had to stop. had FISH again and BMB. hematologist said I was now unmutated I heard from a famous CLL Specialist a couple days ago that mutation status does not change through course of disease either this true and my hematologst doesn't know how to read the report or I am one of those rare people who defy statistics. My advice is make sure of your IgVH status first then find make sure you do NOT have 17p del as FCR will do you no good and instead could do harm. whether being unmutated has the same repercussions as 17p del I don't know. ( maybe someone can help me with this) if I had the choice or using drugs like ibrutinib and zydelg l would choose them a hundred times over than FCR whether I was mutated or not. Since I went all this time under the pretense of being MUTATED and not having BTKS to choose from at the time of first treatment I was given FCR because I was healthy and had good prognostic factors. FCR comes with so many risks during and after. I hope I wasn't too wordy and aggravate you. we all feel the frustration you're having when it comes to choosing the right treatment. if you are able to read online Patient Power CLL they just had a great conference on the treatment plans or you can go and read previous advice given by many hematologists. l hope all works out for you. let us know what you do
CLL IgHV (used to be IgVH) status is a measure of when in the B-lymphocyte lifecycle the CLL clone arises, so in theory it shouldn't change. (The IgHV gene in the DNA becomes mutated as the CLL cell matures and becomes specific to a given antigen. Any further sub-clones inherit the same mutated gene, because as clones, they share the same DNA.) IgHV is difficult to test, so the usual reason for a change in status is put down to an error in the testing process.
While Patients with unmutated CLL IgHV status don't do as well as those with mutated status, they can still have good remissions. From Figure 1 in the October 2015 paper Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia: ncbi.nlm.nih.gov/pubmed/264... you'll see that 75% of unmutated CLL patients remained progression free after around 3 years, (compared with mutated ~6 years) with 50% still progression free after 4 years. 50% of mutated CLL patients hadn't progressed after 15 years with the curve flattening out, hence the exciting possibility of a 50% chance of a cure for IgHV mutated CLL patients treated with FCR.
Neil
Ok so this means I'm still mutated and the test may be an error. I don't know why doc didn't tell me this. I asked him how I could change status but he was angry at how his computer wasn't working right and didn't answer my question. He said stop it! I said are you talking to me? He said no, my computer is giving me trouble. I only went into partial remission with FCR in 2015. My recent cytometry and BMB report said that with the results I would have a shorter time to treatment so this makes no sense to me if really my mutation did not change. Though I am still 13q14 it said that practically all the lymphocytes are 13q14 and this is not good.
IGHV really only divides CLL into two groups.
Things have progressed over the last few years as stereotypes have now been identified in the VH gene... and these have a huge impact on CLL progression and agressiveness.
Unfortunately they aren't tested for outside of very specific genetic research... so we will never know if we are VH3-21 or VH4-39... ☹️
pnas.org/content/112/14/432...
~chris
Thanks I know you will be a little distracted with your own treatment and may not be able to respond to all our concerns. I have had FIsH,BMB,SPEC, cytometry,SPEC urine, and genetic tests! I hope things go smooth for you!
Thanks... I'm not anticipating any side effects... 😃
Your flow cytometry has surrogate markets for IGHV mutation... CD38 greater than 30% and Zap70 greater than 20% means unmutated... with about 70% accuracy...
Direct IGHV mutation is hard to get outside of a major CLL research hospital... so surrogates are used clinically...
~chris
oh goodness gracious I was responding on my tablet and I completely lost what I had already written and now I have to start over again! if I don't get back to everyone at once its because I find I do better if I go and do other things in between so I don't get behind and also take some time to rest and chill out. Here it goes. I agree with the 30% but this is the problem on the test results it reports: cd 38 is 5.75% activated T B, myeloid cells, B cell subset. the front diagnosis says CLL, kappa restricted, markedly decreased myeloid series, poor prognostic markers{see microscopic} and decreased iron stores. then on microscopic it comments : a monoclonal kappa-B cell population co- expressing cd 5 ( 84.38%) and cd 23 present (61.55) abnormal cells 69%. cell size small. moderate cd 20 expression. very dim surface lambda expression. Now on IGVH : unmutated mutation rate : 0% ( I was always told I was mutated. also says IGHV1-69*01 then it goes on to tell you how long you have to live, treatment time, blah blah blah. Next page: no trisomy 12. still del13q14 but it says in interpretation, "as the sole aberration, del 13q14 is associated with a more favorable outcome however, patients with >70% of 13q14 deleted nuclei (as in my case) experience shorter time to treatment. then continues : no p53 del. no evidence of ATM del. but then next line says positive nuclei with p53 del. 3.00% is this a contradiction from the above? Then positive nuclei with del. 11q22.3 0.33% This is the most comprehensive report I have ever seen since dx in 2008. When I started ibrutinib ( apr. 2016 I made him do FISH ( he gave no indication of that he would order it) and when I asked if anything changed (since it wasn't posted on my portal) he said No was basically the same and never said anything about change in mutation status. My only mistake was he didn't retest me at my first treatment with FCR (sept 2014) and instead went on my previous one I had in 2009. I didn't know then, that a person should be tested before each treatment. Since he went to school all those years and I was definitely a novice with all this back then, shouldn't he have told me it would be important to do this? But then I`m reading now of people who are unmutated and or 17p have had to do FCR because that is only thing available and they went into remission anyway. So I guess instead of getting upset because we or them (doc) "should have, could have, or would have", I have to accept it and figure its all water under bridge now. Also the fear of lawsuits hangs over their heads. so basically i`m in "watch and worry" stage right now. Well, that's all for now.
Hi again Chris, I'M not sure I understand. Are you saying because I didn't have my original cytometry test at a major CLL hospital at DX that my IGVH test was innacurate and I was always UN MUTATED? The test was sent outstate. I don't see where on my test it indicates mutation status. I always thought if there was less than 30% CD 38 means MUTATED and on my original test it is about 3% and on my one I just had it says 5.75% Am I looking at the wrong thing? As I said before my first test in 2009 was much less complicated than the one now. ok if this is true that I am really UN MUTATED I will expect my hematologist to spend more time with me or I will have to go somewhere else though I'd rather stay close to home.
I have no idea about your direct IGHV mutation, your doctor should discuss the results.. but genrally if your CD38 percent is less than 30% you would be mutated... however there can be conflicts between surrogate markers and the direct test... which is the gold standard...
~chris
Thanks. I'd be more worried about mutation status if there were no drugs available like ibrutinib and idealasib. Since my doc was not planning on FCR again and I didn't become refractive to ibrutinib I still have it to use and if I have a similar side effect again I can switch to idealasib and if I'm fortunate enough to wait for venatoclax which out of them all I liked the outcomes so far. I don't know if just being MUTATED would qualify me for venatoclax outside a clinical trial.
Yes. Started FCR for 11q unmutated young and fit
I am at Dana Farber and was recommended for FCR with Duvelisib (clinical trial that Dina mentioned). My doctor did not go into much detail about mutated/unmutated - she told me that I fell into the moderate risk category, but not much more. I am unmutated, 65 and fit, so may fall in that gray category of what the best treatment would be. Unfortunately I ended up in the hospital for 25 days after round 2 of chemo due to fevers and extremely low counts. When I finally got out, my doctor gave me the choice of resuming the FCR/duvelisib combo at reduced levels, or going back to watch and wait since my bone marrow biopsy indicated only 10% CLL. I had been reading on this site about FCR and unmutated status and got a second opinion from a doctor who recommended watch and wait. The doctors are guessing I'll get 2 - 3 years before needing treatment again, at which time, hopefully, there will be even better options. I feel great right now, but it's only been 4 months.
Yes, doing fcr now - 3rd cycle.
Hi YjbCLL, I was treated with fcr as an unmutated, 46 year old patient 5 yrs ago. I'm still in complete remission. However, my immune system took a major hit. I was neutropenic for 6 months following treatment, and now my igg antibody count is near zero. Having IVIG has really helped with this! So for me, fcr has worked well for the cancer but left me immunocompromised. Good luck with everything 🙂👍
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