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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
I’m in the process of being diagnosed with an inflammatory bowel disease, the gastroenterologist believes it’s Crohn’s. How often are CLL and an IBD diagnosed in the same patient? I sincerely hope treatment of one won’t exacerbate the other. Do you have any input or recommendations on this disease combination?
Answer from Dr. Furman: CLL and IBD are not two diseases that are associated with one another. Since there is a small, but real, risk for IBD patients developing lymphomas, and this risk is likely increased with certain IBD therapies, it is something that we monitor carefully. There are no data on anything in particular that needs to be done or avoided and the risk is so small that arguably it should not be considered when making treatment decisions.
If someone has a mutation or deletion of T53 and has been taking ibrutinib for the last year with very good results, what is known about the life expectancy in such a case?
Answer from Dr. Furman: The data from a treatment naive cohort suggests approximately 75% of patients with deletion 17p / p53 mutation will remain free from progression. There are 5 year data available for the relapsed patient population with only 25% of patients free from progression at 5 years. I suspect that those patients who have not relapsed by 5 years will likely do extremely well. I also expect the patient population treated with ibrutinib up-front will do even better.
Our most recent advancement, combining ibrutinib and venetoclax together, will likely do the best overall, but the data are not mature at this time.
Regarding the “B Symptoms” of CLL, I can logically guess that the fatigue is caused mainly by low RBC, and the bleeding/bruising is due to low Platelets, and fever/infections are caused by low WBC. Perhaps an overly simplistic on my part, but it makes some sense.
But my lack of medical background isn’t allowing me to logically divine the root cause of the “Night Sweats.” Can you provide an explanation for the physiology and source of that symptom? And for that matter, why they would predominantly happen at NIGHT?
Answer from Dr. Furman: B symptoms, which are called B symptoms just because we distinguished Hodgkin’s disease in stages A and B based upon the absence (A) or presence (B) of these symptoms (fevers, night sweats, weight loss, and fatigue). These are thought to result from cytokines, chemicals the immune cells use to communicate with one another. Remember, there are many people with anemia who are not fatigued. Sometimes, the anemia is caused by the cytokines that might be causing the fatigue.
I started receiving IVIG in September 2016, every 6-8 weeks depending on time of the year. I have been on the Captivate trial since August 2017. When tested in October 2018, I was not MRD negative. I am continuing with both Ibrutinib and Venetoclax. Has Ibrutinib and/or Venetoclax been found to improve the immune system?
Answer from Dr. Koffman: Nothing has been shown to improve the immune system in CLL, an area of research that the CLL Society is trying to encourage and fund.
There are few infections in ibrutinib after the first year in therapy, so that is encouraging and some suggestions it might improve the function of some T cells, but what all that means in a significant way is not clear.
I am about to begin treatment with Ibrutinib @ 420 mg/day. Would 1 or 2 glasses of red wine a few times a week be Okay? Thanks in advance for your response to this question.
Answer from Dr. Koffman: Dr. Furman had already answered this common question on the website in Sept 2018. Here is what he said, which I believe is the answer you were hoping to hear.
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 been diagnosed with CLL for the past year, currently asymptomatic. My blood work had shown slight increases in the WBC since my diagnoses. My general doctor recommended that I look into Low Dose Naltrexone (LDN); he claimed that it has good results on strengthening the immune system. Is there any research on this drug and is it used for watch and wait scenarios?
Answer from Dr. Furman: There are no data supporting the use of naltrexone as part of the management of CLL. There are also no data supporting its use as a strengthener of the immune system.
I have been taking ibrutinib for approximately seven weeks and, as anticipated, my WBC has increased significantly. On average, how long does it take for those numbers to start improving?
Answer from Dr. Furman: The time for resolution of the lymphocytosis varies depending upon the IGVH mutational status, but it is typically 12-18 weeks.
Is there any treatment, natural remedies, or diet plan to restrict CLL in 0 phase and prevent its progression?
Answer from Dr. Koffman: No diet has been shown to slow progression, but there was a study from Spain that showed lower risk of CLL with a Mediterranean diet versus a standard American diet, but we already know that is a healthy diet for just about everyone.
Is having a CT scan for CLL once a year recommended? Is an MRI preferable?
Answer from Dr. Koffman: There is no role for routine annual CT scans unless there are specific symptoms, or it is part of a clinical trial protocol.
MRI has the advantage of no ionizing radiation exposure, but they may also be slightly less precise in measuring the size of nodes and organs.
What advice do you have for CLL patients regarding our risk of contracting measles if we are exposed? Does it matter if we are neutropenic, in treatment, etc.? Do we have to take any precautions about being around children who have recently received the MMR vaccine?
Answer from Dr. Furman: We do not have any data on the safety or efficacy of the measles vaccine in patients with CLL. There have been reports of cases of fatal measles in CLL patients after treatment with FCR, so it is of concern. There has also been a case reported of a death after a measles vaccination in an HIV patient. In essence, there are really no proven safe options for CLL patients other than avoidance.
With that being said, keep in mind that the risk of being exposed to measles is incredibly small and there is a good chance that you will be protected, even if you have CLL. The best way to protect oneself is through herd immunity. If everyone around you is immune, then you are protected. The people who are developing measles at the current time are those who are mostly non-vaccinated. They might transmit the virus to someone who is immunosuppressed, but they would have to come into direct contact with them.
I would add that measles is quite contagious (airborne), so I would obviously avoid the communities that are experiencing a high rate of infections, and also remember the usual good practices of hand washing and avoid touching your face.
I have been on ibrutinib for about three years. Recently, I was found to have microscopic blood in the urine, a medium amount. Cytology test was negative. Ultrasounds saw little cysts. I’ve seen some anecdotal stories about this issue being associated with side effects from the IBRUT. Do you think I should go forward with further testing, such as a biopsy, etc.?
Answer from Dr. Furman: We do have literature on patients who develop microscopic hematuria while on anticoagulation and the recommendations are to go forward with all necessary testing.
Answer from Dr. Koffman: I would add that what Dr. Furman is saying is that the CLL and ibrutinib do not preclude the full workup that would be recommended in any other patient with your presentation who did not have CLL.
I am having issues with EXTREME FATIGUE, along with several other fatigue-related problems. My oncologists have said my numbers, CBC and others, don’t point to CLL being the culprit. Neurological, psychiatric, and viral tests have all yielded nothing. I wonder if I’m just an outlier and having CLL symptoms early. I’m only 52 and dragging myself through even the most mundane activities and haven’t been able to work. When do CLL symptoms start to show up typically or atypically?
Answer from Dr. Furman: Fatigue associated with CLL is most commonly seen when patients have a high volume of disease or have active disease. It is always important to rule out all other causes of fatigue first. Some patients we do empirically treat, if no other source of the fatigue can be identified, in order to see if it improves with treatment. This is only possible because we do have safe and effective treatments.
I also recommend you take a look at this article on fatigue: https://cllsociety.org/2018/09/cll-related-fatigue/
Wouldn’t the body have more trouble getting rid of the higher WBC count growing to 196? So why recommend Watch and Wait when there are newer targeted drugs, like Ibrutinib that FDA approved for first line treatment with minimal side effects?
Answer from Dr. Koffman: Good question, but there is no evidence that early intervention improves outcome in CLL. Please keep a few things in mind, we get treated when we have symptoms or problems, not a high WBC. We can have very high counts and not need treatment, and a significant number of patients will never need therapy, so why intervene even with a relatively safe medication? And ibrutinib works well whatever the WBC.
I have CLL, which is stable and I’m in Watch and Wait mode with no treatment. I have been diagnosed with AFib and it has been strongly recommended to me that I take the blood thinner Eliquis. I am hesitant, since I fear Eliquis might make my CLL progress more rapidly. Should I be concerned about this?
Answer from Dr. Koffman: I know of no evidence that Eliquis (apixaban) accelerates CLL so no worries in that regard. With your doctors and the help of such tools as your CHADs2 score and your HAS-BLED score, determine the best way to manage your atrial fibrillation. If you do need treatment and are considering ibrutinib, then that is a whole other discussion. Many CLL patients are on “blood thinning” and/or anti-platelet meds. This is from the journal, BLOOD: “…, a center-based report of 71 ibrutinib patients with a median age of 73 found that 70% were also receiving an anti-platelet medication, 17% an anticoagulant, usually apixaban for atrial fibrillation, and 13% were receiving both. Major bleeding occurred in 18% of patients, including 78% receiving both antiplatelet and anticoagulant therapy. No major bleeds occurred in this study in patients who were not also receiving antiplatelet, anticoagulant or a CYP3A4 interacting therapy, underscoring the need for care in combining these agents.” Make your best decision about the Afib now and if and when the CLL needs treatment, you can revisit your options.
I’m 37 and was diagnosed with SLL early December. We just had our first baby in October and we are planning on having another one. Right now, it’s hard for me to look in the future and was wondering do/can people in their late 30s early 40s live there average life expectancy with CLL?
Answer from Dr. Furman: There are so many different things that impact prognosis that it is not possible to predict an average life expectancy. More importantly, with novel agents, the average life expectancy is hopefully continually rising. We currently have seven year data with ibrutinib, which indicates almost 80% of patients remain on ibrutinib and continuing to respond. By year 7, these patients have a very small CLL/SLL burden left that one can only hope their risks of complications will be minimal and this number will remain stable for many years in the future. You will also have the opportunity to take advantage of therapies that have not yet even begun being tested. Thus, there is a lot of hope at the present regarding the longevity of CLL/SLL patients.
I would add that there are many SLL patients who will never need treatment and have the same life expectancy as those without CLL/SLL.
I am very sensitive to medications; I feel every change. I want to start on 140mg Imbruvica; Platelets 178000, RDW4.02, and Hemoglobin 8.5. I feel great, will it work for me?
Answer from Dr. Furman: Ibrutinib will only work if there is a therapeutic level present. Starting at a low dose may be inadequate and achieve no benefit.
Will swimming in cold spring water affect my immune system adversely?
Answer from Dr. Furman: No
How long can a patient with Stage 3 CLL go without treatment? What complications can develop?
Answer from Dr. Koffman: Hard to predict, but folks can go many years without needing treatment. The anemia associated with RAI STAGE 3 could be the big issue and if your counts falls too low, that would be a reason to treat. If your nodes or spleen are too enlarged or painful, that can suggest a need for treatment too.
Common complications are due to lower immunity, so infections, secondary cancers, and auto-immunity can lead to low platelets or anemia.
My ALC went from 4.8 to 9.5 in 4 months. Three months later, it was 9.8. I’ve read that doubling time in 4 months should be cause for concern.
Answer from Dr. Koffman: No need to worry about doubling time according to guidelines until your ALC is >30,000. The changes you have are not significant at this time.
I have recently been diagnosed with CLL. I also have several indoor cats. Is this okay, or should I get rid of the cats?
Answer from Dr. Furman: Keep the cats.
I have SLL and have taken about a three weeks of Imbruvica capsules. My side effects so far include joint pain and swelling on my knee and wrist. Will the side effects get better as my body gets used to the medication?
Answer from Dr. Koffman: Generally, those side effects do get better with time, but it can be a slow process. The first few weeks are usually the toughest.
I had 3 CBC tests completed over 6 months and everything was well within the normal range, except Lymphs (absolute), which was 5.4 10(9)/L 5.2 10(9)/L. I had a repeat test from a different lab with a result of 3.4E3/uL. Is this something I need to worry about? I’m a 61-year-old male and healthy in good condition.
Answer from Dr. Furman: There will be lab to lab variation, but more importantly and of much greater significance, there will be day to day variation. These small changes are of no consequence. This is also the reason the Rai criteria places emphasis on the hemoglobin and platelet counts.
What is the best treatment for ITP in CLL client after years of steroid therapy, rituximab, Dep 17 marker?
Answer from Dr. Furman: There are many treatment options for CLL patients with ITP, including rituxumab, ibrutinib, and chemotherapy. The best one depends upon each patient’s particular situation.
Is there anything I can do to prevent the pneumonia, I now have had twice, due to the CLL and Venclexta?
Answer from Dr. Furman: All CLL patients should be vaccinated against pneumococcus, which is the most common type of pneumonia. The other intervention that is helpful are gamma globulin infusions (IV Ig). These infusions of normal antibodies are designed to help protect patients from infections. Given the need for IV Ig to be infused monthly, and associated costs, IV Ig is really only reserved for patients with serious infections.
I’m SLL, and have it growing in my spleen and marrow. My normal is neutropenic and thrombocytopenic. For instance, my last test results revealed a WBC of 2.6, ANC of 0.7, and platelets of 99. It seems a lot of the drugs cause these same issues as side effects, does that limit the drugs available to me?
Answer from Dr. Furman: It is important to remember that the side effects seen with our treatments are relative. We do see neutropenia and thrombocytopenia, but since we typically don’t start treatment until a patient has a platelet count below 100, for example, these side effects are usually well tolerated.
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 Q2 2019.