Treatment FCR with unmutated IGVH—clarify pls!

[gingerlovesal]

My husband is 13q del and unmutated IGVH. In Switzerland they propose FCR treatment and have said outcomes are generally the same. I have read differently. Any insights? Can you direct me to articles? Thank you, his wife

[AussieNeil Partner Administrator]

The figure in this paper clearly shows the difference in outcome for mutated IgHV (green plot) vs unmutated IgHV (red plot): bloodjournal.org/content/12...

Your difficulty may be that FCR is the only government funded treatment available - possibly unless your husband has a 17p del or a TP53 mutation. This is the case in most countries with universal health care - you need to have a chemo based treatment for your first treatment even if statistically you will probably have a shorter remission time if you are unmutated IgHV. So sadly, many of us are in the same situation.

I hope the paper reference helps and would be interested in knowing if there are any other options available to him.

Neil

[gingerlovesal in reply to AussieNeil]

Thanks Neil. You have validated what I thought I appreciate it.

[JigFettler Volunteer]

Hi!

New data is coming out all the time. As Neil says there are some CLL "types" that we know do better. Unsurprisingly mutated do better than unmutated. You need to compare outcomes as they are now newer drugs like Ibrutinib. The whole discussion about the combination treatments adds further to the choice dilemma.

Does your husband need treatment soon?

How much time do you have to decide on what to go for?

I recommend you search this site - there is a lot of information to be found.

Lastly many of us get a 2nd opinion from a CLL super specialist.

Jig

[gingerlovesal in reply to JigFettler]

Hi, your questions are good. He does need treatment now. I’ve been going through the site carefully! There are no super CLL docs in Switzerland and closest is UK but treatment protocols vary and we can’t get visas to UK (to register with NHS etc). Argh!

[Lakanal in reply to gingerlovesal]

No super CLL docs in Switzerland? That is worrying news. My specialist is Dr. France Laurencet in Geneva. She seems to be experienced.

[gingerlovesal in reply to Lakanal]

Ok didn’t know she was CLL super duper but great to know. Merci mille fois!

[Lakanal in reply to gingerlovesal]

Well, I don't know exactly how super she is, as I am still W&W, but so far so good.

[AdrianUK]

Hi there

In the UK we also do FCR with those markers and I had that myself October 18 to March 19. It has abolished my nodes and the disease is not detectable in my bone marrow at the moment.

I’ve been told that as I had a good response data suggests I have 2:3 chance of getting to seven years before needing treatment again. Those who are mutated would have better odds then that.

And for someone who hasn’t yet started the FCR and is unmutated if I remember the number correctly 50% of people will have needed another treatment before four years.

In the UK we only tend to give FCR the once. I would be entitled to either venetoclax in combo with rituximab or ibrutinib monotherapy at second treatment.

Those more selective medicines are sometimes used first line especially in USA. The advantage is that they are usually better tolerated than the FCR.

Did you ask if there were any other treatments potentially available to you or indeed if any clinical trial was possible for you. Not sure on the funding rules for health for you but there will be clinical trials happening in Germany for sure but uncertain if you as Swiss would be able to access that. It’s very possible you might be able to go into an industry trial in Germany tho since the costs are usually met by the pharma company.

Always good to explore your options. But if it turns out FCR is the only choice for you I am walking proof that it CAN work in people who are unmutated. The thought is however that one of the more selective drugs would probably have better short and mid term results in someone with our markers and there is data to support that. Some USA folks get a bit over the top on this and assume that chemo never works for the unmutated which is not true.

It is worth however being sure you aren’t 17p deleted (presumably that would have been tested for you st the same time as your 13q) and also that you are not TP53 mutated (best tested for by genetic sequencing but PCR can also do that sometimes.). Either of these two markers make FCR much less likely to work and so even in the Uk you’d be offered venetoclax or ibrutinib instead.

[gingerlovesal in reply to AdrianUK]

Adrian, what a helpful post. Thank you.

[gingerlovesal in reply to gingerlovesal]

And congrats on your success so far!!

[PlanetaryKim]

Here is a clinical trial that is currently recruiting and has multiple study sites in Switzerland. The trial has multiple arms, but only one of them is chemo (FCR or BR). All of the others are various combinations of the novel agents. So odds are, your husband would get one of those non-chemo arms. It's worth looking into if FCR is all your doctors in Switzerland are offering you, since he may do better with novel agents given his unmutated status.

Trial: clinicaltrials.gov/ct2/show...

kim

[gingerlovesal in reply to PlanetaryKim]

Wow. We were told no sites currently in Switzerland. Thank you!!

[PlanetaryKim in reply to gingerlovesal]

This is the link that should take you right to "Locations" for this trial. And you will see a lot in Switzerland. clinicaltrials.gov/ct2/show... . But you can find it from the main link as well.

[gingerlovesal in reply to PlanetaryKim]

Planetary Kim—the trials in Switzerland are closed. But it was a good chase!

[PlanetaryKim in reply to gingerlovesal]

Oh, so sorry to hear that! On the website all the Swiss sites are listed as "recruiting", and I have not known that website to be wrong before. Did you contact the 2 trial heads in Germany? Good luck, whatever path you and up pursuing.

[gingerlovesal in reply to PlanetaryKim]

Thanks and please NO apologies. It is good to become more conversant with the disease and its options. It all helps build our knowledge. Thanks a million for contributing.

[Shepherd777]

I would be interested to know what percentage of his cells are 13q. Usually if 75 percent or lower they put you on watch and wait rather than treat at all. If you can remain on watch and wait I would do so until other treatments are available that have been mentioned like Ibrutinib or Venetoclax.

[gingerlovesal in reply to Shepherd777]

We will ask.

[gingerlovesal in reply to gingerlovesal]

That was a great tip his 13q is at 90%. So . . . we are treatment bound.

[Smakwater]

Observe the long term clinical data for FCR objectively, and do not dismiss the most up to date comparisons even if they have a lesser history.

The newer data is compelling, and even more exciting research data is awaiting publication.

When observing current data, you should see that in many cases that the responses are nearly similar only out to about 12 - 18 months.

After 18 months is where the contrast begins to accelerate, with unmutated showing poorer outcomes.

As you grow in your findings, please share them.

JM

[gingerlovesal in reply to Smakwater]

Thank you, I like your tone. I appreciate it. And yes we will share as we learn.

[lankisterguy Volunteer]

Hi gingerlovesal,

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I agree with Smakwater's comments, and would only suggest changing one word "poorer" to shorter.

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From my own experience with my UnMutated aggressive CLL, I find that I respond very quickly to treatment. My symptoms, Lymph counts and all blood results return to normal quickly, so treatment is very successful from a "Response" point of view.

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However after treatment is stopped, my CLL will return quickly, so my watch & wait periods are shorter than others.

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I have had 6 rounds of treatment with 4 different drugs since diagnosis in 2008. You can read my treatment history here: healthunlocked.com/user/lan.... As long as medical science keeps finding new treatments faster than my CLL progresses, I will keep surviving.

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Len

[gingerlovesal in reply to lankisterguy]

Thanks Len you're producing evidence that is very positive! Good on you for keeping pace with the discoveries. Thanks for sharing.

[Smakwater in reply to lankisterguy]

I agree.

I borrowed the term from medical summaries and it is not the most accurate word defining outcomes.

[gingerlovesal in reply to lankisterguy]

Len your treatment history no longer exists! Would like to read if you are willing to re-share?

[lankisterguy Volunteer in reply to gingerlovesal]

My treatment history is in my profile

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healthunlocked.com/user/lan...

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You can access anyone's profile by clicking the circled icon with the screen name.

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Len

[tsvieps]

This is financial triage. There are by enough studies that show the newer targeted drugs are superior to FCR in efficacy and duration, especially in combinations. And they have far less adverse side effects. The issue is that they are more expensive. So younger, more vigorous patients who likely can withstand the damage from Chemo will be given FCR by "free" govt programs. FCR usually knocks back CLL for a few years. By then, the newer drugs may be less costly than now. None of this is intended to be what is best for the patient. But the money saved over a few years can be used elsewhere.

Even the money saving may soon prove to be erroneous. Some combo trials, for example Ibrutinib and Veneclax, produce complete remissions for most patients. In trials, such patients with no measurable disease have been able to go up to 18 months so far with no treatment.

Many complain about the costs here in the US, but for older people with serious diseases the care is likely better than under fully govt controlled medicine other countries, where us older people are more expendable. There is simply more bang for the money treating younger people with things like vaccines and pre-natal care.

[gingerlovesal in reply to tsvieps]

And so goes the Big Pharma power. My husband is fit and 63 so on the border but no co-morbidities. We are going with FCR (no choice) and like our colleague Adrian will beat the odds and count on better combos when the relapse happens. Grateful for the contributions of this community.

[tsvieps in reply to gingerlovesal]

Thankfully, the odds are in favor of your husband doing well. I just wanted to point out that economics were as much at play as his well being when he was assigned FCR.

Triage is acceptable in emergencies. We need to save as many as possible with the resources at hand. Financial Triage may also be acceptable and even necessary at times. But it does not feel so acceptable when someone else decides to give me a treatment less useful to me based on costs, even if we need some amount of realism.

The wealthy will often manage to somehow get an edge concerning treatment, no matter how much our politicians scream equal access to the best care is a right for everyone. I am not exactly wealthy, but I did do better than most with my flavor of CLL because I managed to pay with my own resources for "Traditional Chinese Medicine" that was outside the MD centered care that is covered by insurance here, including my Medicare.

Ibrutinib and Venteclax now are available with here with Medicare and "I" was necessary to reverse my progression of CLL. Yet, Chinese Medicine kept me alive for more than 10 years until I could access Ibrutinib. I believe my chances of dieing from delayed access to Ibrutinib would have been much greater if I was living in Britain or Swisserland.

Some of the high costs here for medical are not necessary. But some of the high costs come from being willing to pay more to extend the lives of people with more complex situations. Just comparing overall life expectancies in two countries does not always reveal everything of importance that differ within the two systems.

[AussieNeil Partner Administrator in reply to tsvieps]

It is important to appreciate that your statement that "newer targeted drugs are superior to FCR in efficacy and duration" is currently only true for those with unmutated IgHV - the specific topic of this post. About 60% of those with mutated IgHV have indefinite remissions, now approaching 20 years for early FCR trial participants with mutated IgHV. It's going to take a while yet to find out if we can achieve or better that result with non-chemo treatments. The "far less adverse side effects" statement is sadly not true for many patients in Ibrutinib monotherapy, with 10 to 20% on Ibrutinib discontinuing within 2 years either due to intolerance of side effects (the most common reason) or disease progression.

cancernetwork.com/chronic-l...

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

Ibrutinib is however well tolerated for those over 65 and the incidence of side effects drops away over time:

targetedonc.com/news/ibruti...

Thankfully, we also have quite a few second generation BTK inhibitors under trial (e.g. Acalabrutinib and Zanubrutinib) that look promising with regard to being more selective for B-lymphocytes and hence exhibiting a lower side effect incidence.

Also I consider the current situation of maintenance monotherapy to be a transitory phase. There's a strong focus on combination non-chemo treatments of limited duration, that can deliver complete remissions, such as the Venetoclax and Ibrutinib combination you highlighted.

We need to be advocating for a transition away from FCR for those that are IgHV unmutated, but unfortunately it is still not as clear cut as you portray per the references above. Some of those of us that are IgHV unmutated and are treated with FCR may do better on that than non-chemo alternatives. See mdedge.com/hematology-oncol... Importantly you only have to tolerate the side effects for 6 months!

Neil

[HopeME in reply to AussieNeil]

Neil:

As usual, an excellent fact based response. Thank you for your ongoing efforts to educate folks regarding CLL/SLL and the evolving treatment protocols used to combat the disease.

Best,

Mark

[gingerlovesal in reply to AussieNeil]

Great post again—you Knowledge is our power. Thanks for taking the time. Can’t tell you how much it helps us move forward (and at least for me out of anxiety). Thanks Neil

[tsvieps in reply to AussieNeil]

Yes, and some with mutated IgHV do not need any treatment--they often can be on watch and wait for 15 years without progressing. The person to whom I was replying is unmutated, however. It is true that Ibrutinib does not work for everyone and can have significant AEs like A-fib. But that is also true for FCR and in general the AEs are worse for most and may last long past the treatment time.

I do stand by my main point, which was that more than happens in the US, govt single pay systems are more likely to give FCR for reasons of financial triage, not because of what is in the best interest of patients.

The US is often chided for its costly hodgepodge of medical systems that at first glance seems to provide less satisfactory overall outcomes. But I think we do a better job often with older, more seriously threatened people. Greedy insurance companies are often railed at here. Yet on appeal, I received Ibrutinib before it was even approved for CLL. My doc simply said it could be lifesaving for me based on its then published trial results. The insurance company allowed it and it was lifesaving.