CLL treatment options: I have CLL... - CLL Support Assoc...

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CLL treatment options

drvksethi
drvksethi
17 Replies

I have CLL diagnosed 1 year back. Till recently on watch and wait. Now doctors started FCR chemotherapy because of decrease in Hb. One cycle given. FISH shows Del 13q14.3 30% and 14q32 IGH gene 86% Hypermutated IGVH. Age 62 years also Hypertension and Diabetes. Hb 5.9 TLC 368000 Platelets 68000. Please comment on my prognosis, treatment options, if treatment needs a change, possible Ibrutinib based or Bendamustine, or FR regimen.

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GMa27

Hi fellow warrior!

I was on W&W 12 years till this past summer. 13q mutated age 63. I had 3 IV cycles of FCR. Went very well. Loved my port. After 3 my experts said they would test me. I was in remission and done! BMB and tests showed no CLL in marrow. I hope to be in remission for many years. Ibrutinib was second option. But 65 and older would not have opportunity for FCR and taking a pill for life didn't appeal to me. If I tried Ibrutinib first and decided to switch to FCR, it isn't as effective.

I wish smoothe chemo journey and long remission for you! 💕

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Canuck901
Canuck901
in reply to GMa27

FCR is still a decent choice more people having. Great success with the flair trial of ibruntnib and Venetoclax

1 like
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cajunjeff

It sounds like a treatment decision has been made, fcr, and I wouldn’t see why you would change midstream unless you don’t tolerate the treatment well.

You are definitely in the go category for fcr: 13q, mutated ighv and under 65. There are two schools of thought on what would be best for you.

I think the predominant view among Cll specialists is that folks with your markers have a good chance of a long and perhaps permanent remission with a limited time therapy, fcr would be the choice.

There is a growing minority of Cll doctors that think chemo is obsolete and that people with good markers like you will do just as well on the novel agents like Ibrutinib and venetoclax, with less risk of toxicity.

It could be that combinations of ibrutinib and venetoclax, now in clinical trials, offer limited time therapy too, and outperform fcr.

But that’s speculation while the data on fcr are much more mature. It’s kind of the known vs the unknown.

I think you have made the choice most experts would recommend. Here is an article explaining why fcr is such a good choice for you and why the benefit justifies the risk:

cll-nhl.com/2015/11/fcr-emp...

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RomildaG
RomildaG
in reply to cajunjeff

Thanks a million for this article. It really helped

1 like
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drvksethi
drvksethi
in reply to cajunjeff

Yes, I tolerated first cycle of FCR very well although Cyclophosphamide was given 2 doses only. I don't have 17p deletion. FISH done earlier 1 year back showed 11q deletion also. Latest report has no mention about this. I think they use only four probes.

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EugeneL2

I am not sure whether you had enough prognostic information to start your FCR treatment. It appears that you have 14q32 IGH gene deletions in 86% of the cells examined by FISH test. This is not the same as IGVH hypermutated, which requires a test to reverse transcribe the mRNA to cDNA and sequencing. Your FISH results showed that 86% of the cells did not hybridize with a probe for 14q32 IGH region, this could be caused by the deletion of the DNA fragment in that location, or more likely if I guess, was your IGVH gene went through hypermutation and as a result, the probe did not hybridize well. This would suggest you are IGVH mutated, although further IGVH test is still needed. Finally, your FISH results probably showed no 17p deletion. I would recommend that you also do a TP53 DNA sequencing test to see whether there are any point mutations in the TP53 gene that were not picked up by the FISH test. If the TP53 gene is mutated, one should avoid using FCR treatment. FCR is known to work well mostly in young (less than 65 years old), IGVH mutated, and TP53 normal patients.

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RomildaG
RomildaG
in reply to EugeneL2

I read your answer with interest. I have tried to go online to search but it’s confusing. What is the difference between mutated and hypermutation? Thanks

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EugeneL2
EugeneL2
in reply to RomildaG

I am sorry for the confusion. IGVH gene in CLL usually is either mutated or unmutated. IGVH mutated is above 2% variation from germline sequence, while unmutated IGVH is less than 2%. I believe IGVH hypermutated should be way above the 2% threshold, such as from 8 to 12%. IGVH gene during B cell development also goes through a hypermutation stage after VDJ recombination. It introduces a lot of point mutations (change genetic code locally at a small scale) to achieve antibody diversity and to engage better with future antigens that the antibody might encounter.

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AussieNeil
AussieNeilAdministrator
in reply to RomildaG

Further to Eugene's answer above, I don't like the use of the word mutation with respect to the IgHV gene in CLL cells, because with cancer, we immediately associate mutation with cancer and more mutations with a worse prognosis. So quite often when someone with CLL has their IgHV mutation status tested and finds that it is mutated, they think they are worse off, when actually it is a very good prognostic marker. As you have read in earlier replies, being IgHV mutated: en.wikipedia.org/wiki/IGHV%40 puts you into the desirable category for FCR treatment, where you have a quite high likelihood of a very long remission, even a 'cure'.

Further to the Wikipedia reference above, there are plenty of B-cell blood cancers and they range from acute if the cancer arises early in the B-cell lifecycle, grading to chronic as they happen later on. An important part of the maturation of the B-cell is what's termed somatic hypermutation. It's the T-cell mediated process by which maturing B-cells go through the process of deliberately mutating their DNA structure in the IgHV gene region to produce antibodies/immunoglobulins specific to a pathogen (or vaccine for a pathogen): en.wikipedia.org/wiki/Somat... This is how our immune system develops (up to) lifetime immunity to illnesses that our B-cells can recognise from earlier exposure. (It's also why we can't achieve lifetime immunity to colds and flu because these viruses keep changing their outer coating so our immune system (memory B-cells) no longer recognise them).

For a long time it has been thought that CLL that occurred prior to undergoing somatic hypermutation (IgHV unmutated) was less chronic than CLL that occurred afterwards (IgHV mutated). Recent research may be changing the way specialists interpret this, but it doesn't change the fact that if you are IGHV unmutated, non-chemo treatment is preferable (if available - for many of us it isn't) and FCR is worthy of serious consideration if you are IgHV mutated. Just 6 months (hopefully less) and you can forget about taking anything for your CLL, putting up with side effects, worrying when your maintenance drug will stop working and how you are going to continue paying for treatment.

Neil

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RomildaG
RomildaG
in reply to AussieNeil

Thanks for this. Lola’s (Teresa’s) passing really affected me. I suppose more so because she was a mom, extremely young and with children. Yesterday I read her bio wondering how it all spiraled out of control. I saw she was hypermutated. I assumed it would be better than being mutated. I tried to do a research and got more confused. Especially because my husband is about to start FCR.Your explanation about FCR was exactly the same as our specialist so it really put my mind at ease.

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Smakwater

The Garage doctor version:

One way to view mutational status with regard to IGVH is that in this context mutation refers to the process of reaching full maturity.

Mutated cells complete there transformation to maturity and perform more predictable.

Unmutated cells do not fully mature, and thus add to the chaos of abnormal cell activity.

Go easy on me, Im still in the garage stuck on page 4 of the chilton.

JM

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Zia2
Zia2
in reply to Smakwater

That’s the first time it’s made sense to me Thank you

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Corin850

Hi

Stick with fcr to completion or you have to stop. If you have a choice thereafter I’d take ibrutinib.

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Lavruch

I want to share with you the CLL Society’s Expert Access Program, which provides a free consult with a CLL expert physician after their review of your medical records from your local doctor. You receive a summary to share with your treatment team after the video consultation. It is not meant as a substitute for medical care, but a way to answer questions and receive personalized information. Inclusion criteria includes living in the USA, a diagnosis of CLL, and you are not currently seeing a top CLL doctor; apply for the program here: cllsociety.org/cll-society-...

Please feel free to reach out with any questions to support@cllsociety.org.

Sincerely,

Liza Avruch

Program Director

CLL Society

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drvksethi
drvksethi
in reply to Lavruch

As I live in India, I am not eligible

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Zia2

I’ve learned from here where you live can matter in some ways. Where are you ?

1 like
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drvksethi
drvksethi
in reply to Zia2

I am from Amritsar, India

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