FCR for IGHV unmutated

[Kenn123]

Hi, I've pulled the FCR arm in a clinical trial in UK (was hoping for Ibrutinib). I've been 5 years w and w and haven't received any treatment. Extreme fatigue and large nodes forcing me into treatment. It's only now I've started serious research into FCR and discovered difference between being mutated and unmutated. My doctor doesn't know which I am and has sent off to research centre to find out. Now I'm worried about that. Does anyone know average length of remission after FCR for unmutated types? I haven't got 17p deletion. Any medical papers would be of great interest. Thanks for your support. I'm learning so much from you all.

[AussieNeil Administrator]

I think the best analysis is the CLL8 follow-up study with 8 years of data published in February 2016. The CLL8 study was an large international study by the German CLL group that compared FCR against FC, which given FCR was developed at MD Anderson, provided an independent assessment that established FCR as the gold standard immunochemotherapy treatment for CLL.

Comment on the paper (picks out the highlights and is easier to read) : bloodjournal.org/content/12...

The paper:

bloodjournal.org/content/12...

The information you seek is shown in the first graph of the commentary - where the Kaplan Meier survival curves are shown for FCR treatment of 197 unmutated IGHV patients (red) vs 113 mutated IGHV patients (green). This is a reproduction of Figure 2 in the paper.

Importantly, this is origin of the exciting evidence that IGHV patients that survive for more than 6 years, might be considered cured. (The line flattens out around 7 years after treatment, indicating no deaths from CLL for over half of the 113 IGHV mutated patients treated with FCR.)

Neil

[Kenn123 in reply to AussieNeil]

Invaluable information. Thanks for this. It will help me in discussions with my haematologist next week. FCR or not? Depends on whether I'm mutated or not.

Lorna

[Cllcanada Top Poster CURE Hero in reply to Kenn123]

If know your flow cytometry results, you can get a good indication of mutation status from you CD38 and ZAP70 percentages...

These are indicators, and sufficient for clinical use. You are unlikely to get direct IGHV mutation testing outside the U.S. or a clinical trial...

~chris

[Hidden]

Let me put it in a simple perspective. When I went to MD Anderson for a second opinion, they ran the tests and said that I was unmutated. They said that it would be unconscionable to treatment me with FCR. MD Anderson developed FCR.

[Kenn123]

Can I ask you what treatment you had? I'm horrified that my doctor was going to start me on FCR without even knowing if I was mutated or not. I need to get myself informed quickly.

[Hidden in reply to Kenn123]

Since Ibrutinib was not approved for first line treatment, I was put into a Phase 1 drug trial for ACP-196 (a second generation BTK inhibitor) which has fewer side effects (my opinion). At the time I didn't know how lucky I was.

[MsCLL CLL CURE Hero in reply to Hidden]

I knew I was lucky when I couldn't tolerate Imbruvica and I had this trial to transition to! I hope this drug gets approved soon.

[CAM729 in reply to Hidden]

How long have you been on ACP-196, I started out with it in the first trial using it, but now have become refractory to it.

[CAM729 in reply to Kenn123]

Do you have a CLL specialist, if you have a regular oncologist, I suggest a CLL specialist that does only CLL.

[may04cll]

hey greenview , could you tell me what other test you had run at MDACC ? I'm only seeing a local onocolgist / supposedly hematolgist at the present and I know he isn't up to speed. Four years prior he said FCR for me too . I need to ask him which test's are relevant. Thank goodness that my numbers are still low .

[Hidden in reply to may04cll]

They ran a whole battery of tests including Flow Cytometry and FISH assays. These were standard tests that any hospital or lab can do. Google CLL tests and you can see greater details and explanations.

[Justasheet1]

Ken,

See "Treatment Options for Subsets of CLL" just posted by Chris for some answers.

Jeff

[nkferg]

I am going through this decision myself right now. Another factor is Ibrutinib does not work as well in relapsed/refractory patients. There are more doctors moving away from FCR for unmutated patients, guidelines still have it as primary if you are for fit/young.

[Bubnojay]

Kenn123

Might be a daft question but is your haematologist a cll specialist. ? If not maybe find one, if he is he will be able to answer many questions for you.

Good luck

Bubnjay1

[Kenn123]

Bubnjay1,

My local haematologist is not but I travel to Glasgow to see a Cll specialist. My local doctor has requested my notes (I thought she would have instant access as both nhs doctors). Local doctor does not know if I am mutated or not. I'll be so disappointed if I discover Cll specialist has not done the flow cytometry test before recommending FCR.

So I'm still watching and waiting!

[AussieNeil Administrator in reply to Kenn123]

Flow Cytometry testing is required to diagnose CLL - it's used to differentiate it from other leukaemias/lymphomas. Your CLL specialist should do a FISH test to check whether you have any of the common genetic errors that indicate you'll do poorly on FCR or other immunochemotherapies.

Neil