Ask The Doctor Q4 2018

Questions submitted by readers and answered by the CLL Society Medical Advisory Board

By Richard Furman, MD

I’ve never had or wanted a flu or pneumonia shot, I’m stage 2 CLL/SLL about to start a B-R chemo regimen for 6 months. Friends are urging me to get both. I’m in very good shape for my age other than the cancer. I’ll be 65 on January. Your thoughts, please, Doc?

Answer from Dr. Koffman: Here is the answer from Dr. Furman which I would strongly echo. I would get a second opinion about the BR. Its role in CLL is limited now that we have all of the novel targeted therapies.

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I would add that there are two pneumonia vaccines. Prevnar should be done first. The CDC has a nice guideline for timing of the two pneumonia shots for immunocompromised patients.

Answer from Dr. Furman: He should not do BR.

It is advisable for everyone, especially CLL patients, to receive vaccinations.  While the flu vaccine has to be given each year, we only administer pneumonia vaccines every 10 years.  For that reason, I try to not vaccinate patients for pneumonia within a year of receiving rituximab or chemotherapy.

My husband has been on ibrutinib for 4 years, has been described as being in full remission, and is working with his oncologists on a plan to stop ibrutinib. He has been experiencing some heart problems and significant bruising. I would like to hear about people’s experiences in stopping ibrutinib. Thank you.

Answer from Dr. Furman: We really don’t have any information regarding discontinuation of ibrutinib related to subsequent duration of remission.  We don’t believe that achieving a full remission is adequate for patients to not relapse, given that there still is likely a great deal of disease left.  We do believe that most adverse effects will resolve.  There are other treatments that will not affect the heart, so it would not be necessary to continue suffering side effects from the ibrutinib.

Answer from Dr. Koffman: Let me suggest that he consider asking his doctor about switching to acalabrutinib. It is approved for mantle cell lymphoma, not CLL so it would be off label, but is part of some CLL guidelines, so it could be approved. Acalabrutinib works very much like ibrutinib but may have fewer cardiac side effects. It may also be available in clinical trials for folks not tolerating ibrutinib.

Is CLL hereditary?
My father died of it 10 years ago.
I am now 66. 

Answer from Dr. Koffman: While there is a statistically significant higher risk of first degree relatives getting CLL if a family member has been diagnosed, the absolute risk is very low.

I wouldn’t worry.

I am planning to start on HRT. My oncologist said it was not a problem. I just want a second opinion. I believe he said CLL was not hormone driven/sensitive.

There are no data available suggesting that CLL is hormone driven and no contraindication to hormone replace therapy. 

If a patient who is on non-chemo treatment as front-line therapy (e.g. ibrutinib combo) achieves MRD negative status, would their immunoglobulin levels go up, closer to normal?

At this time, the data does not indicate a clinically significant improvement in immunoglobulin levels with novel, non-chemotherapeutic treatments, but does indicate a decrease in the amount of infections.  We know for chemoimmunotherapy that there will be a reduction in immunoglobulins and increased risk of infections. 

I was Dx with chronic lymphoma/leukemia in early July – after a biopsy of a node under my right arm. I just found a new node – not far from the 1st one. What generally happens now?

CLL is characterized by the slow accumulation of lymphocytes in the blood, bone marrow, lymph nodes, and spleen.  The symptoms of CLL are mostly caused by the CLL cells taking up space.  When the CLL cells fill up the blood, one develops an elevated WBC.  When they fill up the bone marrow, one develops anemia and thrombocytopenia.  When the CLL cells fill up the lymph nodes and spleen, one develops lymphadenopathy and splenomegaly.  Having an enlarged lymph node is typically not a problem.   At this time, the patient is typically “watched” and waits until other signs of disease progression are seen.  This is why this period is termed, “watch and wait”.

Hi, my IgVH test results indicate that I am Mutated, however it also stated that I express IgHV3-21 gene family. The report further states that expression of this gene family in patients with confirmed CLL has been reported to be associated with poor outcome, irrespective of the mutation status. Can you explain further what this IgHV3-21 gene family is and what this means for my prognosis to any treatment (and what future treatments will work for me)? Currently, I am in “watch and wait” status.

In my CLL support group, another woman with this same IgHV3-21 gene family was told by her CLL specialist that this gene family is equivalent to being Non-Mutated in status; is this correct? My oncologist/hematologist indicated that she did not know about this gene family.

Here is the detailed and philosophical answer from Dr. Furman: 

B cells use the IgHV gene to generate the antibodies that they express and secrete.  The IgHV genes all belong to different families based upon some of their similarities and locations in the DNA.  When a B cell rearranges its immunoglobulin genes, it selects an IgHV gene to use.  This is the first step of B cell maturation in the bone marrow.  A second step that occurs in the lymph node after a B cell is exposed to antigen (its target) is somatic hypermutation.  This is a process where the B cell randomly mutates/alters its immunoglobulin gene to make several different versions of an antibody.  Each version has a different DNA sequence, which results in a different protein sequence, and a different target that is bound by the antibody.  This is a way the B cells try to make better targeting antibodies.  This process of somatic hypermutation occurs in the germinal center reaction under the direction of T cells and leads to “mutated CLL”.  

By and large, mutated CLL cases have a better prognosis then unmutated CLL cases.  There are some mutated/unmutated IgHV genes though that seem to result in different behavior than the others of its group.  These V gene families (including 3-21) seem to result in a structural feature that is associated with different behavior and prognosis likely due to the resulting stimulation of the CLL cell.

For VH3-21, which are typically mutated, they do seem to behave more like unmutated CLL.

It is always important to remember that prognostic markers only describe how a population of people will do, never the individual.  There are people on the good prognostic curve who will progress before those on the poor prognostic curve and vice-versa.

As Arthur Conan Doyle quoted in his book, The Sign of the Four:

   “Winwood Reade is good upon the subject, said Holmes.  He remarks that, while the individual man is an insoluble puzzle, in the aggregate he becomes a mathematical certainty. You can, for example, never foretell what any one man will do, but you can say with precision what an average number will be up to. Individuals vary, but percentages remain constant. So says the statistician.”

What are important questions to ask my doctor?

I have recently been diagnosed and been staged. I am very frail and am bedridden.

The most important questions will be related to whether your comorbidities, or the reasons you are so frail and bedridden, are related to CLL or not.  The CLL is very treatable, and if the other medical issues are related, then they might be expected to improve with CLL treatment.

My husband was diagnosed with CLL/SLL about 5 years ago. He had been taking Humara for his psoriasis, something he developed while in Iraq. After the lymph node was taken out his blood work has been stable and no more spikes in his white blood cells. He was receiving disability through the VA but the doctor says now that he has been cured and thought it was just a fluke that he was diagnosed with CLL/SLL from taking Humara. I guess my question is could it have been a fluke? I just know that he had a very large lymph node in his neck, night sweats, and could sleep for hours. I’m so thankful that he hasn’t had any symptoms for the past 5 years, but I worry every time he gets a cough, cold, or sleeps constantly.

Psoriasis is an autoimmune disease.  Humara impacts immune system function.  Both are related to the development of lymphomas, including CLL.

I have had CLL (low risk) about 3 years. Yesterday I received a diagnosis of dry macular degeneration. Could CLL have had any bearing on that diagnosis?

We have no data supporting a connection between macular degeneration and CLL nor any need to treat it differently as a result.

My wife has CLL (no treatment needed as of now) and Limited Scleroderma. We are considering purchasing a hot tub to loosen up her rapidly reduced motion. Are there any health risks for using a hot tub or even hot springs?

There are no concerns with hot tub or hot spring use for CLL patients. 

For patients receiving CAR-T, it’s my understanding that there is an immuno depletion stage via strong chemo, followed by the administering of the T cells. What is the advisability of doing either stage as an outpatient in a clinic setting.

Answer from Dr Koffman: The immune depletion from the chemo is usually mild, just enough to allow us not to reject the CAR-T cells.

Some treatment centers do the chemo and CAR-T inpatient, some outpatient with a very low threshold to admit the patient.

This medication (imbruvica) causes me horrible stomach pain and I have gained more than 40 pounds. WBC is 8.4 and my CT scan showed that the nodes are nearly gone. The oncologist wants me to stay on the medicine. I’m very reluctant. Do you have any advice?

While stomach pains are something we might see with ibrutinib, I don’t believe it could cause a 40 lb weight gain.  I would make sure that no other issues are being missed.   

I was diagnosed with CLL in Nov. 2017 but am being monitored with no treatment as of yet. Had my annual flu shot in Oct. 2018. Is it safe for me to get the first of the two shot new shingles vaccine now?

Answer from Dr. Koffman: CLL patients should never receive any live vaccines. The new SHINGRIX vaccine should be safe. Its efficacy has not been studied in CLL patients but did help other immunosuppressed population, so odds are good it will help us too.

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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 Q4 2018.