Ibrutinib or venetoclax-obinutuzumab

Ibrutinib or venetoclax-obinutuzumab? This will be my first treatment option following CLL diagnosis. Thanks. Happy to provide specific numbers from my chart if that helps.

[AussieNeil Administrator]

I see that you have just joined, so welcome to our community. You haven't shared any background, which will be an important factor in your decision, (age, markers, etc.), but I think you'll find theses previous recent posts pertinent:

healthunlocked.com/cllsuppo...

Some of the major factors going into your decision are cost and how long you want to be in treatment (Ibrutinib is a maintenance treatment, venetoclax and obinutizumab have a good chance of being a limited term treatment). Then there is the travel and coronavirus exposure risk associated with obinutuzumab infusions, plus potentially hospital observation during the venetoclax ramp up phase. Alternatively, there's the cardiovascular risk associated with Ibrutinib, which, as you are US based, begs the question of why not Acalabrutinib? There is still a (lower) cardiovascular risk, but the risk of other side effects is lower too, although we don't have as much long term data as we do with Ibrutinib.

Neil

[Lily_Pad_Master]

Hi MSC11,

It seems to me the truest answer to your question is "it depends". And, although I'm also a CLL patient, intellectually curious, was diagnosed in 2013 and just went into remission after a trial of acalabrutinib, obinutuzumab, and venetoclax, the only thing I know for sure is that I'm not qualified to advise apart from this:

Ideally, you have a doctor/care team who has examined you closely enough clinically, through standard blood tests, and through genetic screening that identifies specific markers to help you answer this question.

I was about to be treated with FCR by a local ENT and Oncologist. Then, my ex inspired me to look outside our mid-sized metro area (i.e. three small cities clustered together with a bunch of suburbs). I was geographically privileged (and because I was privileged to have health insurance through my employer in New York State government), I was able to choose between two of the fifty-one National Cancer institute Comprehensive Cancer Centers (both in the top five) within three hours of my home. I am IGHV unmutated. The local FCR would have meant six months of chemo for maybe two years of progression-free survival. I didn't know there were other options, options tailored to my age, fitness, speed of progression (doubling time and fatigue, in my case) and, most importantly, genetic markers and IGHV status.

If you have that information and post it here, there are some really brilliant people who can tell you what some of that information means. I'm not sure if we have any docs in our community, but if we did, I'm guessing they'd probably be comfortable explaining what the results are testing for, but unlikely to advise.

If you're knew to this "club", I'm sorry. Great community here, bad club to be in. But, in terms of privilege, we have a type of cancer that is being increasingly better managed because of rapid and accelerating research engaged in mutually by brilliant physician-researchers and brave or well-informed (sometimes both) patients. My "handle" here is "LilyPadMaster" because I now see life as a decent-sized pond. It begins on one shore and ends on the other. You can't walk around. Do you swim, or hope it's shallow enough so you can just slog through it? There might be snakes or snapping turtles. I look over this pond, but I'm not at the start. I'm past the middle. Am I swimming or slogging? Nope. I'm at my standing desk, typing while watching one of the Jack Ryan films (the one with Kevin Costner). I'm hopping across on the lily pads. I have to keep moving to the other shore, but I do get to stop on some of the lily pads for various periods of time. Rest. Maybe even sit and dip my toes in the water and feel bliss. Fall in love again. Then I have to move, taking the good stuff with me while simultaneously lessoning my load. Always moving, not willing to drown. I might get to the other shore at basically the same time as my childhood friends, but they are using rafts that were tied to a tree. I was too late for a raft, hence the lily pad hopping. By now, however, I'm a master of it.

Each lily pad is a type of treatment: physical, psychological, emotional, spiritual. The lily pads are sprouting.

Thank you for your post. I've been standing here writing this, realizing how I see my life now. Not at all as I saw it seven years ago, at 51. 51 was a number. 51 + 8 years as a CLL patient = Damn. I'm mortal! Thinking about how to respond brought this up. I needed to feel it a little. Thank you.

You'll get some good answers.

Glenn

[Hidden in reply to Lily_Pad_Master]

Thank you so much for the thoughtful answer. I’m so new this; learning the terms and acronyms. Although my oncologist provided those two options, I’m receiving second opinions from a couple other major medical centers as well. I’m leaning towards the V-G option as a relatively healthy 47-year old guy. Many thanks!!

[thompsonellen in reply to Lily_Pad_Master]

Love the lily pad metaphor. And good advice to get to a major center, if possible.

[BallparkChaser in reply to Lily_Pad_Master]

Great post Glenn.

[prbild]

While both seem to be viable options, your post says you are waiting for FISH test results and it may be important to have these to get a complete picture before making a decision. Since you are in the US you can also get a no cost second opinion from a CLL specialist through the CLL Society (cllsociety.org/cll-society-expert-access/) that could help guide you.

Paul

[Hidden in reply to prbild]

Hi Paul. I do have the FISH results as well, which were negative. Any specific markers I should look for?

[prbild in reply to Hidden]

The FISH test looks for abnormal chromosomes that are very common in CLL. The most influential is a 17p deletion, although with the newer treatments you mention, it is not as important as it once was. I'm a little surprised with no FISH markers and the report you posted that treatment is being recommended at this time. CD-38 positive characterizes the disease and is generally associated with being IGHV unmutated which can indicate a shorter time to needing treatment, but I'm not sure if it, in itself, is a cause for treatment. Treatment is usually dependent on your Rai Stage (0-IV) which factors in your lymphocyte count, lymph node/liver/spleen enlargement, hemoglobin level and platelet count. A good introduction to all of this can be found at the National Comprehensive Cancer Network (NCCN)

nccn.org/patients/guideline...

You should discuss with your doctor the need for treatment as well as the type of treatment.

Paul

[AussieNeil Administrator in reply to prbild]

Hi Msc11,

Further to Paul's reply and per your addendum to your post, being CD38 positive is not an indication to start treatment. You haven't shared enough for us to work out WHY you are being recommended for treatment now. I strongly recommend you ask for the reason per the NCCN guidelines, etc,, per this post: healthunlocked.com/cllsuppo...

FISH testing is used to check for 17 p del, but that's not relevant with your proposed treatments, since you are presumably assumed to have unmutated IGHV from your CD38 positive result, hence the suggestion of treatment with targeted therapy (non-chemo) drugs. (If chemotherapy was being considered, then you should have been tested for normal TP53).

Staging is not used to decide when to start treatment with CLL, but gives some guidance on the likely time before treatment may be needed. After diagnosis at stage IV, I lasted 11 years in watch and wait before starting treatment.

As you live in the USA, you should be able to access a free consultation with a recognised CLL specialist for a second opinion via the CLL Society's excellent Expert Access program: https:cllsociety.org

Neil

[Hidden in reply to AussieNeil]

Much obliged.

[Hidden in reply to prbild]

Thanks for the input, Paul.

[SERVrider]

As has been said above, Ibrutinib/Acalabrutinib are inhibitors, taken orally, which prevent leucocytes dividing excessively and turns back "on" their natural apoptosis (dying off after a proper time). They don't "cure" CLL but control it and have to be taken for the rest of your life. At $15,000 a month, your insurers may jib at that cost, especially as you're only 47. Obinutuzumab + Venetoclax work differently and are generally given over a 6 month course and can be expected to put you into long-term remission from the symptoms. Obinutuzumab is given intravenously so that means doing it a hospital that might be full of Covid-19 patients and the first treatment is usually pre-treated with IV paracetamol and an anti-histamine (Benadryl) and then spread over two days. You then have to go back for more on day 8 and again on day 15 of the first month's cycle. Thereafter, it is only one IV administration a month.

You probably can't (or shouldn't) have Obinutuzumab injections in a GP's surgery (Doctor's Office) because the data sheets say that for the first dose, there has to be resuscitation equipment available. OK, it is "just in case" but none the less it is a potential risk.

[Hidden in reply to SERVrider]

All good info SERVrider. Luckily my home hospital is fairly COVID free!!

Speaking of financial implications: this was an interesting nudge model developed to compare costs for insurance companies; link.springer.com/content/p...

[Hoffy]

I am a fan of V-O since the combo can many times get people to enough remission to get off all drugs for a while. Imbruvica alone usually can not achieve that results.

Be well,

Hoffy

[Hidden in reply to Hoffy]

Many thanks!

[Hidden]

FYI. There is now reason to believe the CLL diagnosis may not be 100% accurate. Second opinion doc is reviewing slides from lymph node biopsy, so my question may be a moot point. Thanks!