Confused about treatment option

[Kotek]

Hi was diagnosed 10 years ago on watch and waiting... 2 months ago I had hemolytic anemia now ok after prednisone,but treatment on horizon.I am unmuteted no 17p only good one 13qI live I Ontario and this qualifies me for treatment with Imbruvica I am 67 years in good health otherwise.My onc feels that FCR is better option for me instead of lifelong Imbruvica ,that is confusing since chemo is very toxic would love feedback from our community and thank you

[AussieNeil Partner Administrator]

Can you confirm that you are not 17p deleted, but are unmutated and have 13q deletion? If you are unmutated, you are unlikely to achieve as long a remission on FCR as you would if you were mutated, but drug side effects will only be of concern for a limited time, not indefinitely. While you say "chemo is very toxic", the short and long term effects of FCR are well known and not considered as bad as other chemo treatments. You don't lose your hair for example.

Neil

[Lola69 in reply to AussieNeil]

Neil can you explain why I as a mutated and non 17P deleted only got a 20 month remission on FCR? I’m shy to ask my doctor. The other day I bumped into the nurse that did the FCR infusions on the chemo floor. had been 2-3 did not see her. So I said “ hello remember me?” She’s always surprised to see me. No idea why. Maybe she thinks I should be dead by now. ... so I asked her “ did u infuse me with water? her response was “ everybody says that”. I am not done with her ..

[AussieNeil Partner Administrator in reply to Lola69]

CLL is very complex with respect to its drivers and we only concentrate on the influence of the better known ones in deciding treatment. (Not that you had as much choice when you had treatment as you have today). I doubt you had enough testing done for anyone to give you a definitive answer of why your remission was disappointingly short. Bear in mind that while there is a significant difference between the median remission times for IgHV mutated and unmutated patients, the distributions do overlap. That means that for some like yourself, remissions can be shorter than for an unmutated patient.

As to why that happens, clonal evolution is happening all the time and treatment is going to select out sub-clones that are resistant to FCR and may be more aggressive. You may have had a small proportion of aggressive sub-clones prior to treatment or they could have arisen during treatment. Without having blood samples taken over time analysed for changes, we'll never know. Importantly, your remission lasted long enough for you to have Ibrutinib available for you when you needed it and that's what really matters.

Neil

[Lola69 in reply to AussieNeil]

Very in depth explanation. I know that before I started FCR I had lymph nodes in the back of peritoneal sac and when I relapsed with FCR the peritoneal sac was not filled with nodes. I believe FCR did help me enormously but was not for me. It may actually be the cure for others though. Thx Neil

[Thermoformer in reply to AussieNeil]

How does trisomy 12 fit in I am supposed to have some sort of chemo soon trisomy 12 was on my fish in 2016

[AussieNeil Partner Administrator in reply to Thermoformer]

With trisomy 12, if you are mutated, you have a very high probability of a very long remission or even a cure on FCR, according to Dr Sharman:

healthunlocked.com/cllsuppo...

Neil

[Thermoformer in reply to AussieNeil]

Don’t know about mutations what test would that be?

[lankisterguy Volunteer in reply to Thermoformer]

The most common "mutations" are also called prognostic indicators, and those are identified with a FISH (fluorescent in situ hybridization) test.

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onclive.com/publications/on...

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Here is a well written but dated explanation of prognostic indicators, note that the survival curves are obsolete- data from long before the modern targeted therapies were approved. This long, illustrative and often humorous article from Chaya Venkat of CLL Topics includes an excellent explanation of mutated v unmutated IgVH and is in a form many will find easier to understand

updates.clltopics.org/3256-...

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Len

[Kotek]

Thank you Neil I had FISH done and no 17p deletion but there is extra TP53 onc doesn’t know what that really means I hope is something good since elephants have extra 20 of TP53 and that’s why they don’t have cancer ha ha have to keep positive mind keep well

[PlanetaryKim]

I am in BC and have been on Imbruvica (ibrutinib) 13 months, after first having a single cycle of FR. I am glad to be on the Imbruvica. For me that is preferable to any kind of chemo since chemo drugs are, by definition, cytotoxic, and ibrutnib is not. I may be eating my words down the road if there are discoveries of bad effects from long-term use of ibrutinib. But at present, I am not experiencing side effects. Good luck to you!

kim

[Cllcanada Top Poster CURE Hero in reply to PlanetaryKim]

Imbruvica (ibrutinib) is cytotoxic, perhaps you mean myelosuppressive? Although the jury may still be out on that...

cytotoxic agent listen (SY-toh-TOK-sik AY-jent)

A substance that kills cells, including cancer cells. These agents may stop cancer cells from dividing and growing and may cause tumors to shrink in size.

cancer.gov/publications/dic...

~chris

[PlanetaryKim in reply to Cllcanada]

I was under the impression that ibrutinib and the other targeted small molecule drugs to not kill any cells.

[PlanetaryKim in reply to Cllcanada]

"Unlike cytotoxic chemotherapy, which attacks all rapidly dividing cells, targeted therapy is directed toward precise pathways thought to contribute to the growth of cancer cells."

ncbi.nlm.nih.gov/pmc/articl...

[Cllcanada Top Poster CURE Hero in reply to PlanetaryKim]

Ibrutinib is an orally administered, highly potent, selective, and irreversible small-molecule inhibitor of Btk.

It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity.10 Ibrutinib also abrogates the full activation of Btk by inhibiting its autophosphorylation at Tyr-223.

This inhibition prevents downstream activation of the BCR pathway and subsequently blocks cell growth, proliferation, and survival of malignant B cells.

ncbi.nlm.nih.gov/pmc/articl...

Sure different mechanisms of action than chemo, or EGCG, or venetoclax.. but ultimately the result is apoptosis...the B cells die. So..cytotoxic.

[Kotek in reply to PlanetaryKim]

Thanks!

[alpek in reply to PlanetaryKim]

Hi,

We are also in BC and want to get my dad on Ibrutinib, unfortunately it is not funded as a first line treatment unless you are 17p deleted. Can you let me know how you were able to receive it/funded? Was it because you couldn't tolerate FCR after 1 round?

[PlanetaryKim in reply to alpek]

Hi alpek. I replied to your private message with longer answer. But yes, I got ibrutinib on a funded basis because they felt it wouldn't be safe to give me a 2nd cycle of chemo (FR in my case). When I say 'they" I mean all the CLL specialists at BCCA-Vancouver because they conference all their cases, and I was told by my specialist that they all collectively signed off on the request for me to get ibrutinib. So I would say it's in your best interest to be seeing a CLL specialist at BCCA-Vancouver. My specialist there is Dr. David Scott.

[cajunjeff]

This is a personal and not a professional opinion, but I would personally choose ibrutinib over fcr if I was 67 and had unmutated Cll.

In the recent abstract report on ibrutinib for first time users, at 7 years out, 80% or so of the people using it have not progressed. I think that will turn out to be a longer remission than unmutated cll-ers get with fcr, with much less risk of toxicity.

I don’t agree ibrutinib is necessarily a life time drug. I am on it now and believe my doctor will soon add another drug, probably venetoclax, to get me in remission and off therapy for who knows how long.

Some doctors are now predicting with the early data from the ibrutinib/venetoclax trials that the remissions they are seeing with that combo will be as or more durable than fcr remissions.

There is data to suggest ibrutinib actually restores our immune systems to some extent. Very few first time users are resistant to ibrutinib and for most the side effects are tolerable.

With fcr or ibrutinib you will likely need another treatment down the road. I would choose the least harm now approach to be as healthy as possible for your next treatment.

This is just a lay opinion on what I would do, not advice for what you should do. FCR is a more proven treatment with more data to support it. There could be toxicities yet to be known about ibrutinib. A lot of very fine Cll doctors still use fcr.

But you asked for opinions and mine would be to choose the daily pill. I am biased as it’s the treatment I am on.

My only real advice would be to get a second opinion from a Cll expert. There might be very good reasons that fcr is a better choice for you.

[cllady01 Former Volunteer in reply to cajunjeff]

bassejm,

Do you have a link for the abstract?

[cajunjeff in reply to cllady01]

Dr Furman discusses here how ibrutinib can outperform chemo and has high percentages of disease control 7 years out:

m.youtube.com/watch?v=WOfqc...(Not working as expected?)

Check out the graph in this study at 7 years out for first time users. I think it’s an amazing curve. It’s a small cohort, but 80% pfs is nevertheless impressive. What will it look like at ten years? Can people keep their Cll under control indefinitely with a pill a day? We will see, but this study supports Furman’s opinion that ibrutinib might be all some people ever need. I don’t want to be on a pill the rest of my life, but I would sign that deal today if you told me it would keep working.

ash.confex.com/ash/2018/web...

[Kotek in reply to cajunjeff]

Had 3 opinions last one from CLL specialist all advised FCR I am not convinced since I am 98% IGHV Unmuted will search further thank for responding

[Lola69 in reply to Kotek]

Listen to your gut! It’s usually spot on!

[HopeME]

Kotek: Is it possible for you to get a second opinion? This is a very complex disease with lots of changing options on treatments. If possible seeing a CLL specialist is the way to proceed. There are so many divergent opinions it really is well worth the effort.

[Lola69]

Hi Kotek! I live in Montreal , Quebec Did FCR in 2014 I’m not 17 P , mutated and only had a 20 month remission. Each case is unique but it’s very well tolerated. In my case I only stayed in bed 2 days a month. Vomiting mostly. Only u and your doctor can make an informed choice. In Montreal they only give imbruvica to 17P patients or as a second line Tx if FCR fails the patient. .. good luck!

[Kotek in reply to Lola69]

Thank Lola I just look and Imbruvica is approved as first line of treatment for pt with IGVH unmutated like me hope I am right some dr are not aware yet since this regulation passed in December 2017 ps I really admire you joy of life !!

[cllady01 Former Volunteer]

This site, a Mayo Clinic (THEMATIC REVIEW SERIES ON NEOPLASTIC HEMATOLOGY AND MEDICAL ONCOLOGY published in May, 2018 has a treatment strategy flow chart for CLL.

Contrib: Drs. Strati, Jain, and O'Brien.

mayoclinicproceedings.org/a...

The chart is on the 6th page of the publication. It shows the treatment for someone: Fit, non-17p del, and/or unmutated IGHV to be FCR.

[Lola69]

Don’t they also have to be under 65?

[Lola69]

U don’t lose your hair. It’s chemo immunotherapy

[Cllcanada Top Poster CURE Hero in reply to Lola69]

Yes it is full blown chemo, only the drugs used do not cause Alopecia , but nitrogen mustard and purine analogies certainly are chemo...they just don't have the hair loss side effect.. like say vincristine.

~chris

[Lola69 in reply to Cllcanada]

The F&theC are chemo but not the R

[Lola69 in reply to Cllcanada]

Does Bendamustine cause alopécie? When I relapsed they wanted to give me B/R but something about not funded in Montreal

[Rpshe1 in reply to Lola69]

Bendamustine does not cause alopecia. I am unmutated & was Trisomy 12. Dr Sharman recommended a study of his of Bendamustine & obinutuzumab. Treatment ended April 2016...30 months ago and doing great!

[Lola69 in reply to Rpshe1]

Lucky u to know Dr. Sharman. Thx for the info but B is mustard gas right?

[Rpshe1 in reply to Lola69]

It is, but lighter & more tolerable than F&C (which Sharman did not recommend for me). Imburvica was approved halfway through my treatment. Sharman said he still wouldn’t have recommended it if it was available me. He’s a fan of the combo drugs (one to flush out the cells, the other to mop up the lagers). I was more concerned with quality of life than longevity. I was 60 when I needed treatment. Sharman feels I could get 5-7 years before needing treatment again. I’m shooting for 10

[Lola69 in reply to Rpshe1]

Congratulations and always important to have a long term goal thx for sharing

[AussieNeil Partner Administrator in reply to Lola69]

Bendamustine development resulted from the observation that mustard gas selectively killed lymphocytes. It is a related chemical compound.

[Lola69 in reply to AussieNeil]

And kills healthy cells too. . Chemical warfare still being used today!

[Cllcanada Top Poster CURE Hero in reply to Lola69]

Bendamustine was develped in the old Zeiss factory in Jena, DDR. It is a compound based on nitrogen mustard gas (mustine) , and it has a fludarabine like purine analog ring attached... so its a combination of FC in one drug. Its been used in the former Soviet Union for ~ 50 years, but only came to the West 10 years ago...

Useless history...

~chris

[Kotek in reply to Lola69]

Thanks I really like my hair

[Lola69 in reply to Kotek]

I like my hair too! While they were trying to figure out which subtype of lymphoma I had I was researching the cold penguin caps. U put them on and u don’t lose hair. Was happy I did not need the caps for FCR Here is the link polarcoldcaps.com/?gclid=EA.... FCR did however make my scalp very sensitive to this very day though.

[Lola69]

Correct Len! The F&C are not mild at all! I assumed that since they gave it with Rituxin was not as full blown as the other chemo drugs where people lose their hair.

[DriedSeaweed]

I suppose my concern would be that after FCR it is possible to have worse mutations and deletions. 17p could suddenly show up.

It sounds like ibrutinib puts pressure on the clones and nastier ones could thrive. My question to a doctor would be what sort of abberations have been shown to develop on ibrutinib?

[Cllcanada Top Poster CURE Hero in reply to DriedSeaweed]

Here is a good paper on clonal evolution and Imbruvica (ibrutinib)

bloodjournal.org/content/12...?

And a commentary

bloodjournal.org/content/12...

[Newchallnge]

Hi Kotek, I am not a doctor, but I understand that people that are UNmutated do not do well on FCR. Since you are 13q deleted which is good, I don’t know of that offsets being unmutated.

But I don’t now.

This is AN an absolute scenario where you need a second opinion not from the community oncologist who does all types of oncology, but a CLL specialist. The doctors oath is “fist, do no harm” - get a second opinion!

[Kotek in reply to Newchallnge]

Thanks I went to one but will seek another opinion

[Big_Dee]

I know how you feel. I will start BR treatment on 15th of November. I am 71 so FCR was off the table. FCR is the gold standard for treatment. I to could have chose Imbruvica as I am also un-mutated, 13q deleted. I did not want to contend with the many side effects of Imbruvica even though I am in good health. If FCR does not give long remission then you can follow up with Imbruvica, but not the other way around. I wish you well on your decision.

[cajunjeff in reply to Big_Dee]

From all I read the doctors are trying to figure out, in the new age of novel therapies, what is the best sequence to use. I think to do BR first and save ibrutinib for any relapse is a reasonable strategy that might turn out to be the best sequence. They just do not know yet. People who take ibrutinib front line are doing much better on average than those who take it as a second treatment, so only time will tell.

I think the trend is away from using fcr for unmutated patients. Dr Furman doesn't use chemo at all for cll. Dr Sharman, who has a great reputation in the cll world, appears to not recommend fcr for unmutated cll. In a 2015 article he said the risk of marrow damage doesn't justify the relatively short remission.

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

He suggested using BR frontline for unmutated back then. That was before ibrutinib was approved frontline and before the new data showing how effective ibrutinib is frontline.

I think its fair to say that a lot of good doctors still use fcr frontline for unmutated cll. Kotek wrote that all three of his doctors have recommended fcr.

I have seen 4 doctors along the way. The first suggested BR. The second FCR. The two true specialists I saw both suggested ibrutinib.

So if experts who know way more than we do can disagree, its reasonable to think patients will have different opinions for their choice.

There are a bunch of great trials going on now with the novel agents. There is a decent chance we see venetoclax approved front line soon and that venetoclax plus gazyva for a year and then stop will become the new gold standard.

Its great we have options, but hard for each of us to know which one is best when even the best experts disagree.

[Big_Dee in reply to cajunjeff]

Right on in your analysis. My CLL Specialists agree, but leave the choice up to me. Being un-mutated means I may not have a long remission, but yes there are some very promising treatment options which may get through trials when if/when my relapse occurs. I also talked to a doctor at MD Anderson who had rough draft of ibrutinib data which shows un-mutated 65+ patients remissions of 6 years. The full study is to be published in 2-3 months.

[Hoffy]

I would do Imbruvica. FCR harms your bone marrow and immune system.

“The times are changing”. Imbruvica combined with Venetoclax are bringing most people to MRD negative.

I would think Canada May allow people the combo in the not to distant future since it will same money if people get off all pills.

Be well,

Hoffy

[Kotek in reply to Hoffy]

Thank you I am theoretically candidate for Imbruvica but doctors in Ontario are under duress from the province so they are not too eager to prescribe it however I will insist and find a dr who will apply for the the drug for me. ps 50%of my income went to taxes after all go many years

[Curling123 in reply to Kotek]

Where are you in Ontario, Kotek? I am in Toronto. Hoping if I need therapy it will be Imbruvica. Ontario seems to be lagging behind in approving cancer drugs, considering it is the largest province. Shame on them. Are you on watch and wait for now?