Questions submitted by readers and answered by the CLL Society Medical Advisory Board
By Richard Furman, MD
Can a tickly cough be a side effect of ibrutinib?
A tickly cough has not been reported in the clinical trials, (which does restrict adverse events to those usually occurring in greater than 10%), nor something I have seen in my clinical practice.
A tickly cough is often a result of post-nasal drip, something CLL patients often have due to chronic sinus issues.
If MRD results are .03% and 4 months later are .06% (both by bone marrow), are they virtually the same due to low levels even though there is a 15x increase?
There is always a variability with any biologic assay. Additionally, you need to keep in mind that the MRD assay is a percentage and does not necessarily translate into a different amount in absolute terms.
I initially had about 50% Trisomy 12p when first diagnosed and — after a couple of years — my CLL “evolved” to include 8% 17p deletion (just over the threshold of diagnosis of 7.5%). I started on ibrutinib and my blood test numbers became almost completely normal range across the board. We did a recent FISH test, though, and my 17pdel is now up to 18% and my Tri 12p is down to 16%. It seems strange that the more benign marker went down while the nefarious one climbed. What do these shifting numbers mean and does that indicate I might be more likely to fail on Ibrutinib, which has been working so well for me?
It is important to distinguish percentage from absolute numbers. All of the CLL might be undergoing apoptosis, but the trisomy 12 ones are more sensitive and therefore undergoing apoptosis quicker. Therefore, by killing them at a different rate, you are changing the percentage. As long as the absolute numbers are decreasing, you are still responding.
I was diagnosed with CLL in 2004, and starting chemo (FCR) on Monday 8/20. What can I really expect and is it unrealistic to believe I can continue working through treatment? I am a registered nurse working bedside on a med/surg/tele floor.
FCR chemotherapy is typically well tolerated. The primary toxicity involves low blood counts, mostly neutropenia (low WBC), but that is well tolerated and usually not noticed by the patients.
Please let me add my own comment as a fellow patient. – Brian Koffman
The role of FCR in treating CLL is very circumscribed. Unless you are IVGH mutated and have other good prognostics, I would not recommend it. And even in those circumstances, I would probably look to another option.
If this is your first therapy, take a look at this survival data for ibrutinib. FCR doesn’t come close.
Please consider getting a second opinion before starting FCR. We have a list of CLL experts on our website and if you reach out to me I can help guide you.
If you do go ahead with the FCR, most patients without 17p deletion or p53 do respond and for chemotherapy, it is generally well tolerated as Dr. Furman points out.
Hi – I was diagnosed with CLL (and SMZL) 4 years ago. Prior to my diagnosis, I received antibiotics (through the years) for various bacterial infections. I had no problems with any of the antibiotic families. Since I was diagnosed, I’ve had a couple of infections and needed an antibiotic. When I take antibiotics (now), I have an unusual delayed reaction. About 7 days after beginning a course of antibiotics, I develop a high fever (103F), get a headache, have flu-like symptoms and my blood counts are impacted… my lymphocyte count falls dramatically as does my white count and my platelet count. When I stop the antibiotic, my symptoms disappear, and my blood counts rebound. The only antibiotic that now works for me (without causing a reaction) is Cipro (ciprofloxacin). Because of Cipro’s known side effects, I’d prefer not to be solely dependent on it – I’ve tried the penicillin group, tetracycline group, and Zithromax family. Any thoughts on what is causing my (alarming) reaction to antibiotics?
This is an unusual reaction to antibiotics. There are many different mechanisms of reactions for patients, so it is hard to tell without knowing all of the details. A seven-day course leading to low blood counts does sound like the time course for bone marrow suppression due to the antibiotic with a resulting infection from the neutropenia. This is all something that could be evaluated for so that a group of safe antibiotics could be assessed.
My husband was just diagnosed with CLL this past week. His white blood count (WBC) is 2.8. Is there any medication that he can get to help increase his WBC count? Also, is there anything that would help his fatigue? hemoglobin (HBG) is 12.
There are many causes of a low WBC and fatigue. What to do to help depends upon the cause. -Brian Koffman
I was diagnosed with CLL 5 years ago. I am Stage 1 and have a WBC of 17k. I don’t have any issues with 11q, 17p or TP53. I have been taking vitamin supplements, but I have gone back to a multiple every day. Still, I wonder if certain supplements might help. During my reading I came across Neem, which is a tree where different parts of the plant are used for a variety of health issues, including CLL. Has anyone heard of this or is this a scam? It claims to cause Bcl2 apoptosis…
This is a very important question. There are no data of any supplements being able to help control or prevent CLL. Many have been studied, including resveratrol, curcumin, and ECGC (green tea). There was a change in the laws in the mid-90s that allows natural products to be marketed as food supplements instead of as pharmaceuticals. This allows claims to be made without having to substantiate them or obtain approval from the FDA. In essence, they can state that Frosted Flakes are great (Tony the Tiger) without proving it in a randomize controlled clinical trial.
My belief is that taking a multivitamin is a good idea (no data supporting its necessity). I also believe vitamin D supplementation is important, as studies suggest 70% of the population is vitamin D insufficient without supplementation.
There are some suggestions that vitamin D levels may have an impact upon cancer risk and risk of progression of CLL. I don’t believe these have been substantiated but do know a level above 30 ng/ml is necessary for preventing osteoporosis and is important to target.
I had Flow and FISH done. Is it so important to get a bone marrow done also at stage 0 WBC 20 ALC 15?
The general guidelines do not recommend a routine bone marrow biopsy at the time of diagnosis, unless there is lack of clarity on about the diagnosis or some complication. – Brian Koffman
I have CLL and was on imbruvica for 32 days. My lymph nodes went normal immediately. I got switched to venetoclax due to bad side-effects. After 4 days of 20 mg my lymph nodes are swollen not as much, but swollen under both arms. Is it normal? Does it happen when meds are switched?
Venetoclax 20 mg is a low dose and it is likely that the CLL cells have started to grow. They will typically be taken care of by the higher doses. The most important thing is that your physician re-evaluates your tumor lysis risk prior to escalating to the next dose so that they can take any protective measures necessary. I also suggest talking to your treating doctors.
I’ve been taking Ibrutinib for a year now with good results except for rather severe photo phobia and repeated uveitis episodes. I’ve been prescribed 15mg of methotrexate per week as well as 2.5 mg of folic acid per week to reduce inflammation and control the uveitis.
My question is whether methotrexate can cause secondary cancers like some other chemo therapies can and whether it is worth the risk of taking this drug for this purpose?
Methotrexate is not one the chemotherapy agents associated with treatment related MDS, but it is associated with Richter’s transformation. This dose is quite low, so the likelihood is probably low.
One question though, is whether the ibrutinib might have been related to you developing the uveitis. It is theoretically possible. Given the plethora of agents now available for CLL, using a different option would be possible.
I’m having a good deal of trouble controlling my weight while on ibrutinib, despite a lot of exercise, eating healthy, etc. And so I’m wondering why? Does it cause fluid retention, or is this associated with toxins? If so, can you suggest anything I can to improve the situation re: unwanted weight gain?
There really are not data regarding weight gain while on ibrutinib. Fluid retention has been seen, but this should be discernible on exam. It will be important to make sure there are no other explanations for the weight gain.
My husband’s FISH showed: trisomy 12 in 60% of nuclei AND IGH/BCL2 fusion, t(14;18) in 53.8% of nuclei. His absolute lymphocyte count has more than doubled in 5 months to 29.8724 with his WBC count at 32.47. At present, he is exhibiting no B symptoms. His other important blood values are low but within normal limits except LDH which is high. His nodes are quite small.
We know this sub-type of CLL is very rare, but we have been given no information as to what to expect. What is his prognosis with these markers? Any other recommendations?
While trisomy 12 is a typical interphase FISH abnormality seen in CLL patients, the translocation involving BCL2 and IGH genes is not. As a result, we do not have any behavior or prognosis associated with this translocation in CLL. While trisomy 12 has certain prognostic implications, there is no better indicator of prognosis than how the disease evolves over time.
I have been taking Ibrutinib for about 1-1/2 years. Started getting rashes on legs and arms. Does sun cause this to happen?
At the present time, ibrutinib has not been associated with photosensitivity, although, any drug could theoretically cause it. – Dr. Koffman
21 days of doxycycline seems to be the standard Lyme disease treatment. Is an extended doxycycline treatment recommended for CLL patients with Lyme?
There are no indications that treatment of Lyme disease needs to be different for CLL patients compared with others.
I was diagnosed with CLL a couple years ago, but I have had it for about 10 years as my WBC continued to grow higher. My question is why does the WBC fluctuate up and down? So far, I am on a watch and wait and have not had to have any treatment.
CLL cells circulate between the blood, bone marrow, lymph nodes, and spleen. They do most of their dividing in the lymph nodes and then circulate for periods of time. Small changes in cytokines (proteins that cells use to communicate with one another) can change their propensity to circulate. This is why no treatment decision should be based off of a single rise in the lymphocyte count, but should look at the hemoglobin, platelets, lymph nodes and spleen, and changes in the lymphocyte counts over time.
I was diagnosed with SLL/CLL 12 years ago. My past treatment includes Rituxan, bendamustine, Imbruvica, obinutuzumab with chlorambucil, and now ublituximab with umbralisib. I started having joint pain while on Imbruvica. Pain went away when I went off it. Last year I took obinutuzumab and did well, but only had a 6-month remission. In January of this year I started a clinical trial of Ublituximab and Umbralisib. The joint pain returned, and I am in constant pain: my back, hips, shoulders and knees. My doctors keep telling me I have arthritis. I have had several steroid injections, I go to physical therapy 3 times weekly, and take a lot of ibuprofen. I have a hard time getting around, have to use a cane to walk and am in constant pain. Does anyone have any suggestions? I am a 70-year-old woman; I can no longer ski, hike or play golf. My hematologist insists it is arthritis. I really need help. Thank you very much.
The biggest question is whether the joint aches resolve with holding the umbralisib and ublituximab. It is important to remember that both agents might be associated with the joint aches. (We see joint aches with rituximab and obinutuzumab.) If the joint aches do not resolve with holding the agents, then it is likely unrelated.
I have been treated with venetoclax for the last 18 months with good results-MRD negative in bone marrow and blood. I have PT 53 mutation. My IGG levels have been high up to 10,000. My hematologist who is a well-known CLL specialist has never seen or heard of this occurring. All tests for other problems like lupus or myeloma were negative. Have you seen or heard of elevated IGG levels with CLL?
Only about 5% of CLL patients will have hypergammaglobulinemia. Given that you are MRD negative, it is unlikely that the IgG production is from your CLL cells. I suspect it is from a second process. It is important to determine if the IgG is monoclonal or polyclonal, with monoclonal being more indicative of a lymphoma/myeloma and polyclonal more indicative of an inflammatory process, such as lupus or Castleman’s disease. The 10,000 level is quite high and should be further evaluated.
I am in a clinical trial at MD Anderson for CLL with 17 Deletion. I’m on ibrutinib and venetoclax and doing well. Would it be more helpful if I give up drinking any alcohol? My doc says not a problem, but I wonder. I have a glass of wine nightly and weekly will have a martini. Some nights I have 2 wine.
There is no interaction between the alcohol and the ibrutinib and venetoclax, both in terms of its efficacy or its safety. There is also no interaction between the alcohol and CLL.
I have CLL with a mutation of p53. I have been taking Ibrutinib since March 2018, so far with incredibly fast and positive results with most of the blood work coming in within the normal range (including the previously high cholesterol level which is now within the normal range).
My question is whether fasting of any kind is safe, unwise or definitely prohibited whether for the Jewish Day of Atonement or intermittent fasting.
There is no contraindication to fasting while one is on ibrutinib. Whether it is safe or not depends upon where one is in their therapy. If they have a great deal of disease, maintaining hydration will be very important.
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 Q3 2018.