Imbruvica-related issues: Qs + comments

[Pogee]

The following are questions and comments I'll be asking my oncologist when I see him tomorrow. I believe at least some of them might be relevant to what some among us are experiencing and research some of us are engaging in. Clearly, none of the comments here are meant to be authoritative nor intended as medical advice. I encourage you to research any of these questions and comments on your own, if you feel they may be relevant. Bless you all. P.S. I've had a great day today after having a good night's sleep on 10mg of Valium, stopping all of my many vitamins and supplements, downsizing to 140mg of Imbruvica, and drinking about a gallon of water.

* As you know, I’ve had a severe adverse reaction to Imbruvica. I sincerely appreciate your responsiveness last Monday, and your being so patient and forthcoming with me—and I have a lot more questions and comments for you today! First, since dropping down to 140mg and taking it during the day instead of at night, I’m generally feeling better.

* There’s a scholarly site that lists potent and moderate inhibitors and inducers of the liver enzyme CYP3A4. Here’s a list of them for you to keep. It’s important because one of the supplements I was taking was quercitin, which is a potent inhibitor. What this means is that it wasn’t allowing the liver to properly process the Imbruvica, which had the effect of increasing the dosage. I’ve been feeling somewhat better since taking it out of my daily vitamin intake, and I’d like to think there are a lot of other people out there who are having adverse reactions to their meds, at least partly to things they’re ingesting that they have no idea are causing adverse reactions, in combination with their targeted therapy medication.

* In fact, starting Tuesday, I’ve stopped all my vitamins and supplements to see if there might be any other inhibitors or inducers I’ve been taking that I doin’t know about.

* Although I’ve dropped down to 140mg, I’d like to continue having refills at 280mg, in the hope that my adverse reaction was the result of a combination of Imbruvica and the CYP3A4 inducors, so I could hopefully up the strength to 280.

* You should know that on Tuesday evening we saw my primary physician, Dr. A_________, who gave me a 5-day supply of 10mg of Valium. I took it Tuesday night, and slept very well.

* There’s a scholarly site that notes that when a person has had an adverse reaction to Imbruvica, he should go back on it at a lower dose. The site also says that with each incidence, the dose should be decreased until the fourth one, when the person should be taken off it completely. Have you come across that information? I could send you the link, if you want.

* If I were to stop taking Imbruvica, would that likely mean my CLL would stay the same or even advance more quickly?

* What physical issues might I be facing, if I stopped taking medication?

* What’s my prognosis, in your opinion, if I go off Imbruvica?

* Looking back at my blood results, it seems that my white blood cell count shot up specifically because of the Imbruvica—which you said would happen. * Before taking it my WBC count was about 20,000. * After taking it the count rose to nearly 80,000 immediately. * What was the purpose of starting this treatment, if my levels were going to go so high—especially if there would be a chance I wouldn’t be able to tolerate the Imbruvica well?

* My WBC count has been going down modestly over the past couple of months—to 50,000 now. * If I keep taking the Imbruvica, what level might we be able to hope that it could go down to? * If I stop taking it, does that mean my WBC level won’t go down any more?

* If I were to stop taking Imbruvica and develop what’s known as Imbruvica withdrawal syndrome—according to an Imbruvica site, 25% have developed withdrawal symptoms—and then started taking Calquence or Venetoclax, do you know whether I would still get Imbruvica withdrawal symptoms—along with possible symptoms from the new drug?

* I’ve read that Calquence is considered the second generation of Imbruvica and that it generally seems to be at least as well tolerated as Imbruvica. Have you come across that information?

* Is there any reason why we started on Imbruvica, instead of Calquence?

* Is Venetoclax also considered a second generation drug? How does it compare to Imbruvica and Calquence in terms of results and side effects?

* What about Idelalisib, which I’ve read is well tolerated?

* If I were to discontinue Imbruvica, which other drug would you recommend? Whichever it might be, I’d like to start at a lower dose than typically recommended.

* What do you think of CBD oil for my agitation? Do you know whether this might be considered an inhibitor or inducer?

* Would you provide me with a medical card that I could use at a legal dispensary? * What types of things do they dispense?

* What do you think of using mushrooms, such as Reishi, lion’s mane, and cordyseps, which in various studies have apparently shown great promise in treatment of CLL?

* What do you think of EGCG, the active ingredient in green tea, which numerous studies say has demonstrated substantial apoptosis in CLL cells?

* I’ve read that chronic CLL is described as asymptomatic, symptomatic or progressive, refractory, or recurrent. * Which category am I in?

* You started this treatment because you said my CLL was at Stage 2. * You said my lymph nodes are enlarged, but my spleen is fine and my liver apparently only shows something small but undefined. * What organs, specifically, has it reached?

* How badly compromised are they—or were they the last time I was able to do the CT scan? * Do we even need a CT scan at this time? Wouldn’t the WBC level and other CLL-related blood labs be sufficient?

* If you think I need a new CT scan, are there any open CT machines I can use that offer high quality imaging? * What about an MRI? * Dr. A_________ suggested I ask you about a serial MRI. Is that a possibility? * By the way, thank you for prescribing the atavan for me, which I’m hoping I won’t need next time around.

* Speaking of blood labs, I would appreciate your prescribing a new series of dates for the next few months.

* Is external beam radiation an option, since CLL cells are apparently highly susceptible to radiation? What advantages and disadvantages might that have compared to Imbruvica? * Is this something we can consider, since it’s targeted and potentially has fewer side effects?

* Is flow cytometry of any value to us in terms of analyzing and/or managing my CLL?

* What about immunotherapy, or CAR T-cell therapy?

* What about leukapheresis?

* What about a bone marrow biopsy?

* I’ve read that ketamine can be very emotionally uplifting. * Can you prescribe it? * Could you prescribe it as an off-label treatment?

* Are you willing to respond to emailed questions and/or comments?

[Davidcara]

Hi Pogee, not sure where you are located, but here in the US, not always enough time in an appointment for all your questions. In addition, sometimes the answer to a question leads to other questions and long discussion. What I usually do is research the questions that I have, to see if I can find some answers on my own. Although, I am a nurse so have a good understanding of medical jargon. I would say, I would ask your questions in order of importance to you. This way, if everything does not get answered, you could ask your lesser important questions at a later date.

[Pogee in reply to Davidcara]

Thank you for your comments. I plan to spend as much time as necessary in the oncologist's office. Her may try to kick me out—I suppose that's his option—but I have no intention of leaving until satisfied. Bedside manner and consideration for patients is, in my mind, equally important with knowledge. In fact, over my nearly 8 decades, I've found that too many doctors should be ditch diggers, for all they know (not!) or care (not!). We'll find out about this one soon enough. As an aside: Q: What's the difference between God and a doctor? A: God doesn't think he's a doctor!

[Davidcara in reply to Pogee]

Good Luck Pogee. Will be thinking about you. You take care

[Pogee in reply to Davidcara]

Best to you, too!

[shazie]

Most probably he won’t have straight answers to most of your questions. Each patient reacts differently to Imbruvica. Let us know how your appointment goes.

[PlanetaryKim]

Good questions Pogee!

Fyi, CBD is a CYP3A4 inhibitor. Whether it is a weak or strong one, I am not sure. But I think I recall seeing some reference listing it as a "potent" CYP3A4 inhibitor. I feel I had a bad ibrutinib reaction once because of this, and I stopped using CBD. I was only applying the CBD topically, but still it does get into blood stream. (Btw, I take Ativan occasionally for stress/agitation and find it really effective with no downside if used occasionally.)

As for your lymphocytes shooting up after starting ibrutinib... That is actually a good thing and what you want to see. You are not acquiring more lymphocytes as a result of ibrutinib. rather, the ibrutinib is driving them out of lymph nodes and into blood stream where they will die. The rapid increase in lymphocytes is a sign that ibrutinib is doing a really good job. However that initial die-off from all those lymphocytes driven into blood stream could perhaps result in some side effects that won't persist later once blood levels of lymphocytes are lower.

As for why your were started on Imbruvica instead of Calquence... in many places it's just a case of the way the funding rules are established. Some countries/jurisdictions may not have Calquence available as first treatment. Or Calquence may only be available as first treatment if Imbruvica is contra-indicated. For example if person has pre-existing afib, that might be basis for starting with Calquence instead of Imbruvica, which is known to cause or worsen afib in some people.

Good luck with your doctor's appointment. Hope you get some answers.

kim

[Pogee in reply to PlanetaryKim]

What a comprehensive reply, Young Lady! Your comment about CBD oil confirms my understanding of inhibitors and inducers, which is why I believe, without specific evidence, that if one takes one or more inducers it might well be appropriate to downsize one's dose of the targeted therapy drug, be it Imbruvica or another. * You're correct about the elevation of WBC levels following initiation of these drugs. I was clearly informed of that before starting Imbruvica. * Thank you for your explanation regarding why I was started on Imbruvica and not Calquence. I'm from the US, have Medicare and Empire/Blue Cross/Blue Shield. However, I'm not familiar with their requirements. On the other hand, I notice that Medicare is reimbursing Imbruvica's Pharma—I hope you're sitting down for this!—$12,000+ per month! And, at least so far, I'm not paying a cent, not even a copay. * As for my doctor's appointment...stay tuned. Best to you.

[PlanetaryKim in reply to Pogee]

That's great that you don't have to pay anything for your Imbruvica in US. a lot of US patients are paying some co-pay. So good for you!

Re: CYP3A4 interactions...

a CYP3A4 inhibitor will INCREASE imbruvica in blood, and a CYP3A4 inducer will decrease Imbruvica...

Because it is not the Imbruvica that is being inhibited or induced... but the liver enzyme (CYP3A4) that is required to metabolize and remove imbruvica from the body. So less of that liver enzyme means more imbruvica in blood stream for longer.

Best to you too Pogee!

[Pogee in reply to PlanetaryKim]

We're in complete agreement on this. That's why I think it might be beneficial to consider taking, for example, a specific amount of Reishi Mushroom, which is a potent inducer, and reduce the amount of Imbruvica, which could decrease the side effects, while maintaining the effectiveness of the Imbruvica. Just thinking out loud. Best to you!

[PlanetaryKim in reply to Pogee]

I know what you mean. I considered gambits like that too at one point - how to decrease my necessary ibrutinib dose by taking a cyp3a4 inhibitor like grapefruit daily.... The problem is you really have no clue at all how much ibrutinib you are or are not getting into your body that way. At least with the prescribed dose (or really I would say with the formula for calculating minimum therapeutic dose, which is 2.5 mg ibrutinib per kg of body weight) you know you are getting > 95% BTK occupancy. And that's what you need.

[Pogee in reply to PlanetaryKim]

I hear you, and appreciate the calculation you've provided, which I was unaware of. I'm 175 pounds, or 80kg, so multiplying that by 2.5 would put me at 200mg. So, it's a blessing that I was never at 420mg, which is what the doctor initially prescribed. But having had adverse reactions at 280, and now being fine at 140—having also modified other habits—I think I'm in a good place. Also, for what it's worth, I've read that people whose CLL is more moderately reduced, as opposed to more rapidly, have better long-term outcomes. Therefore, if true, I'm more than happy to have a slower recovery. Moreover, having recently gone through not only severe adverse reactions but likely clinical depression—my father committed suicide when he was 33—I can't possible explain to you what a relief it is to not be "there."

[PlanetaryKim in reply to Pogee]

So sorry about your father's suicide - and so early in his life.

I too have read the speculation by some researchers that reducing the CLL slowly rather than rapidly creates less pressure for resistant sub-clones to form. That notion guided me too somewhat in my choice to dose reduce the ibrutinib. But mainly I wanted to forestall side-effects (like the afib) for as long as possible so that I could get as long a run as possible from the ibrutinib. I knew I was not a person who would keep taking a daily pill if I was having bad side effects.

[Pogee in reply to PlanetaryKim]

We think alike, Young Lady. I find as I get older—now 77+—my willpower has faded even more than mum mental acuity. I find that particularly distressing. As for my father, he contracted dystonia, a progressive disease similar to ALS, at a young age. He committed suicide in 1945, when I was 2 and my sister 4. My mother, just 27, somehow managed to survive through the darkest of times, then succumbed to CLL herself in 1992 at age 74. Some people worship the Kim Kardashians of the world. I worship my mother.

[PlanetaryKim in reply to Pogee]

Is your profile photo a Scottish Highland cow? Very nice!

[Pogee in reply to PlanetaryKim]

I have no idea where that photo came from!!! Do the administrators simply give you one when you don't have one? By the way, I'm really not much of a bull. After a hundred years of marriage, my wife has pretty well neutered me. lol

[PlanetaryKim in reply to Pogee]

hahaha!

[Newdawn Administrator in reply to Pogee]

No we don’t allocate avatar pictures Pogee or I’m sure we’d have given you something more majestic than a bull! 😂

Newdawn

[Pogee in reply to Newdawn]

Mooooooooooo.

[Rt2000]

Out of respect for other patients waiting to see you doctor, tell them you have many questions and would like a longer appointment. We all know how aggravating it can be to have to wait long past one’s appointment time because previous appointments run long.

[Pogee in reply to Rt2000]

Good suggestion. Thank you!

[Hidden]

Holy Moly, that's a heck of a list.

And understandable.

Dealing with CLL can be overwhelming, and your list seems to represent this quandry.

While your doc would be a very desirable resource for at least some of these answers, posing this many questions at once makes it near impossible for those being questioned to provide you answers.

Personally, while I would love to help try to provide you resources to find your answers, such a wall of questions leaves me wanting to run and hide; there is too much there to take the effort to parse.

Many of these questions have already been answered on this fine forum. Taking some time to do the homework may be worth your while. If you learn to fish, the result can be more productive than being given a fish.

Perhaps also without flooding this forum with single posts for every question at once, you could prioritize and pose one at a time.

[Pogee in reply to Hidden]

Thank you for your comments. I only posted the questions and comments I was planning of giving to my oncologist. Take from it what may be of any value to you. I had done sufficient initial research to ask the questions, but obviously needed my oncologist's input. In fact, we had our meeting this morning, and it was very positive. He didn't need to respond to every question, because we arrive at understandings long before the end of the list. As for posing one question at a time, please understand that the questions weren't meant for anyone on this forum to answer; only for folks on this forum to consider researching on their own or asking their own oncologist, if they felt it warranted a response from their own doctor.

[Hidden in reply to Pogee]

Fair enough,

Just a person who feels compelled to help when I can, but I can only deal with a bite at a time!

Sounds like your understanding with the Dr brought some sort of partial closure or at least reduced sense of urgency... Glad.

[Pogee in reply to Hidden]

Thank you for your kind thoughts. Yes, a reduced sense of urgency. However, I must say a good part of that, and of my feeling of wellness over the last couple of days, has resulted from cutting my 280mg imbrutinib in half, taking it during the day instead of at night, cutting out all my vitamins, and drinking a very large quantity of water daily. Importantly, my primary physician gave me a five-day supply of 10mg of Valium. I took it and slept wonderfully the first two nights. Last night I didn't need it and slept very well. So much of our physical, mental, and emotional well-being is inextricably intertwined!

[MsLockYourPosts Passed Volunteer]

I’m glad that your appointment went well. I’ve learned over time to try, when I have a lot of questions, to prioritize them and make 2 copies - one for myself with room for notes, and one for my doctor. He can often see where I’m going with my list and offer more complete answers.

With a longer or more complicated list I send it ahead of my appointment day. Looking at your list I can see questions that your doctor could probably combine to answer and, as a result, give you a more complete understanding of, for example, how your treatment was decided on, or what the best options are moving forward.

[Pogee in reply to MsLockYourPosts]

My oncologist was kind, thoughtful, patient, and thorough. He gave me a copious amount of time, without rushing me. He's flexible and amenable to suggestions. We agreed on a course of action that I feel comfortable with. Naturally, he doesn't recommend any herbs, mushrooms, or other supplements, nor did I really think he would. On the other hand, he didn't dismiss them dismissively. Overall, I think I'm in the best place I can possibly be under the circumstances, and I can only wish the same for you and all others on this site.

[wmay13241]

Ibrutinib caused my wife to have horrible, horrible leg and hand cramps plus AFIB/ There are well know Ibrutinib side effects.

[Pogee in reply to wmay13241]

I'm sorry sorry to hear of your wife's adverse effects. I understand from my oncologist that acalabrutinib/Calquence, even though a second-generation targeted therapy drug, may have even worse side effects. He recommended did Venetoclax. Unfortunately, sometimes we're between a rock and a hard place, and we can only pray we're making good choices with the most beneficial outcomes under the existing circumstances. Our thoughts and prayers are with your wife.