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Questions submitted by readers and answered by the CLL Society Medical Advisory Board
Remember that we cannot give medical advice and any suggestions should be reviewed with your treating doctors.
By Richard Furman, MD
Upon searching online, I find very little information about how ibrutinib affects fertility and how to proceed to start a family. I have found a little bit of information on http://drugs.com/pregnancy/ibrutinib.html about a trial in animals. But the research focused on how the medication affects the pregnancy in the female when given doses of ibrutinib. Are the amount of toxins transferred from a male taking the medication to a pregnant woman minuscule? I also cannot find any information if ibrutinib have any effect on my reproductive qualities.
Answer from Dr. Furman: We do not know the risks related to ibrutinib and pregnancy. Some of the enzymes that are inhibited do likely play an important role in fetal development. With that being said, you are correct that the amount of ibrutinib transferred in semen is likely minute but is also unknown.
Can International flights effect your blood counts being lowered? Every time I travel internationally, my test results are dramatically lowered, and take months to regain the previous count levels? Aware that prolonged travel can cause DDT’s, is there a similar effect on CLL?
Answer from Dr. Furman: There are no data that traveling internationally could impact your blood counts. Remember that the WBC is only one parameter, and arguably not the most important, of disease progression. Hope that helps I think you meant DVTs, not DDTs.
Can mutation status change like the FISH markers?
Answer from Dr. Furman: No. Mutation status is the one prognostic marker that does not evolve during the course of CLL.
While taking Venclexta and rituxamib, can you drink wine?
Answer from Dr. Furman: Yes
Answer from Dr. Koffman: Let me add all things in moderation.
What information do you have regarding the association between untreated CLL and osteoporosis? I have found a few articles but still looking for any other info that I can find.
Answer from Dr. Furman: There currently are no known associations between CLL and osteoporosis.
Is there any relationship (cause/effect) between my frequent bruising and skin tears, where I bleed just beneath the skin, and CLL? I have numerous dark purple areas on my hands, arms, and lower legs where I have hardly touched something, and I start to bleed.
Answer from Dr. Furman: There is no association for CLL and bruising / bleeding unless the CLL is resulting in a low platelet count. CLL can cause a low platelet count by either infiltrating the bone marrow and interfering with platelet production or by inducing an immune response against the platelets and causing their destruction (ITP). It is important to have your platelet count checked in this situation.
Bleeding and bruising can be the result of a low platelet count (thrombocytopenia) or of platelet dysfunction. Aspirin is the most common cause of platelet dysfunction. The CLL would only cause bleeding and bruising if it lowered your platelet count sufficiently, usually below 50,000.
To that I would add that ibrutinib can cause easy bruising and bleeding.
I just watched the video with Dr. Neil Kay about early treatment and prognosis. He mentioned that IVIG treatment is controversial but didn’t say why. I’d like to know what the controversy is.
Answer from Dr. Koffman: There are guidelines on when IVIG should be given, generally when both your IgG levels are < 400 mg/dL and you are getting 2 or more serious respiratory infections annually. That said, many doctors will give IVIG more freely for any kind of recurrent infections and some doctors will almost never recommend it. That is my understanding of the controversy.
Results from ASH 2018 indicated that rituximab does not add significantly over ibrutinib, but when used CONCURRENTLY! Should ibrutinib come first, then followed by rituximab or obinutuzumab? The paper also speculates about the use of anti-CD20 maintenance therapy after cessation of ibrutinib. Another piece added to the puzzle!
Answer from Dr. Furman: It is important to recognize the value of in vivo (in body) versus in vitro (test tube) data. The in vitro data for ibrutinib plus rituximab has shown added benefit and interference. All that ultimately matters is the clinical data. The current data demonstrates no difference between I versus I+R, but that does not mean that they are equivalent. The data only shows what it can show based upon the numbers of patients, follow up, etc. This was a study (FCR vs IR vs I) that was powered to look for statistically significant differences.
I was diagnosed with CLL about six months ago. My doctor has informed me that I have 17P deletion and I am to start Imbruvica next week. I’m thinking of asking my doctor if we can go back to watch and wait. Would you please let me know if that would be a good idea?
Answer from Dr. Koffman: Having a bad prognostic marker is not an indication for treatment. Many folks with 17p deletion can go years with no treatment needed.
See this article on when treatment is needed: https://cllsociety.org/2016/03/cll-watch-wait-start-treatment/
If you don’t have an indication for treatment as outlined in the article, then hold off until you do.
What are your thoughts with medical marijuana and cancer?
Answer from Dr. Furman: Medical marijuana has been shown to be helpful in alleviating some symptoms of pain and nausea. It has not been shown to be particularly helpful with cancer.
Can you point me to a link or list of the suggested markers/tests that a newly diagnosed patient with CLL/SLL should get?
Answer from Dr. Koffman:
There is some controversy about which tests to do when in CLL patients.
We believe you must know your IgVH mutation status, FISH and TP53 before any treatment, but not all guidelines say you need to know at time of diagnosis.
That is a shared medical decision between you and your doctor.
Here are some helpful articles with links to more info on what tests might make sense:
Hope that helps.
Are there adverse effects after stopping ibrutinib?
Answer from Dr. Furman: There are no adverse effects from discontinuing ibrutinib, except that if the CLL was progressing, it is possible the disease might accelerate in its rate of progression. This is because ibrutinib will still have a partial effect on inhibiting the CLL, even when its progressing. When you remove the “partial break”, the CLL will be able to grow at its full rate.
I have been diagnosed for over a year with SLL. Only problems that I’ve had have been an intense reaction to bug bites. I transported myself last week to a place where there are more bugs and I had something bite me that produced a big hard lump on the back of my neck at the base of the skull. As that subsided after 5 days, a lump appeared a few inches in front of it. I took it to be a lymph node. It grew increasingly painful. And I am currently experiencing intense pain from it. To the point where I can’t sleep. Is there anything to do?
Answer from Dr. Furman: I have found that some patients with over exuberant responses to insect bites might harbor an antibody to the IgE receptor. This antibody is a type of autoimmunity that can lead to excessive immune cell activation and histamine release. I have successfully used rituximab to treat patients if the antibody is present to reduce its presence. Otherwise, histamine blockers and steroids are helpful.
This may be a question of nomenclature more than anything else.
I had a recent (and first) FISH test completed, and the major finding was: “POSITIVE for deletion 13q14.3 (30% of cells).”
While my reading at the CLL Society, and elsewhere, would indicate that this is GOOD news, (compared to some of the alternatives), my doctor said he needed to study up on that particular version of del13 before he could give me a full prognosis for likely progression of my CLL.
So, my question: Is the terminology “del13q14.3” just a more scholarly way to say “del13”, or are there variations of del13 which could be more concerning? My novice studying-up on the topic hasn’t revealed any significant discussion of del13 variants… but it may be a more esoteric topic than what you might find on the web.
And, depending on your answer, should I be concerned if my oncologist is not immediately able to handle this question?
Answer from Dr. Furman: 13q deletions do vary depending upon the lab that performs them, but all clinically licensed labs will cover the region on chromosome 13 that includes 13q14 which is where two genes that produce micro RNAs are located that are responsible for regulating bcl-2 production. It is important to remember that a single deletion at 13q is only a good prognostic when it is the sole abnormality present.
My father is on Ibnutrib 280mg per day which is an adjust dose to avoid comorbidity. I am really concerned because his doctor told him he can take the medicine twice daily instead of once daily. That is 1X140 in the morning and 1X140 at night! I will be really grateful if you could let me know if Ibnutrib would this way. He has been taking Ibnutrub for more than a month now.
Answer from Dr. Furman: One of the reasons ibrutinib is tolerable is that the its half-life is approximately 4 hours. The enzymes that are irreversibly inhibited, like BTK are turned off for good. There are many enzymes that are reversibly inhibited that are turned off for only four hours. If ibrutinib were to be take twice daily, then these other enzymes would be turned off too long and would likely result in increased toxicities.
My wife started Ibrutinib a month ago and experienced all kinds of muscular pains moving throughout her body plus lower belly cramps, so her quality of life is close to zero. Her hematologist told her to take painkillers which doesn’t seem right in the long term. Can we expect the side effects to become more bearable with time? Should I ask her doctor to lower the daily dose?
Answer from Dr. Furman: Diffuse body aches, called myalgias, are an adverse event related to ibrutinib. They are probably seen in some extent in 5-10% of patients on clinical trials. They most commonly are not as debilitating as your wife’s seem to be. I typically treat patients with low-dose prednisone with some efficacy. After 4 weeks, the prednisone can be tapered without recurrence of the symptoms.
Richard Furman, MD is Director of the CLL Research Center at Weill Cornell Medical College and a member of the Lymphoma/Myeloma Service in the Division of Hematology/Oncology. He is a member of the Medical Advisory Board for the CLL Society.
Originally published in The CLL Tribune Q1 2019.