I am currently on ibrutinib first-line for my CLL (Trisomy 12, 13q), and it is working very well in my first three months. If I reach complete remission, or better still MRD negative, can I stop taking the ibrutinib and see how long the remission will hold? Could I go several years drug-free, rather than lifelong drug-use?
The current information we have regarding ibrutinib is that someone should remain on it as long as it is working and it is well tolerated. We know that even if someone were to be MRD negative, that there is still likely significant amounts of disease left. Allowing this disease to grow back could lead to more aggressive disease than was present previously.
Minimal residual disease is achieved when less than 1 out of 10,000 cells is a CLL cell (< 1 x 10-4). Some groups have made estimates regarding the duration of treatment that might be necessary to achieve “cure” beyond MRD. This is estimated to be at a level of 1 out of 100,000,000 (< 1 x 10-8). Calculations suggest that the time to achieve this level of depletion is equal to double the time it took to become MRD negative. Thus, if one becomes MRD negative on ibrutinib after 7 years, an additional 7 years will be required to achieve “cure”.
While these calculations are all of great interest, the guiding clinical principle is that the risk for adverse events decreases over time (with the exception of hypertension) and if there is clinical benefit, than it is worth continuing treatment.
I have osteopenia/osteoporosis, in addition to CLL. Prior to my recent diagnosis of Stage 0 CLL, I was receiving Prolia injections every 6 months. Does this treatment conflict with my CLL, as it targets the bones and growth?
There is no contraindication to using Prolia for your osteoporosis in the setting of CLL. CLL can rarely be associated with osteoporosis, but almost all osteoporosis seen in CLL patients will be the routine osteoporosis of aging. It is important to use whatever therapy is best to treat the osteoporosis.
My partner, a previously very fit and active man, now 65 was diagnosed with CLL in March 2014. He was asymptomatic and blood levels were good, so was on watch and wait. However now he now CNS involvement (3 lesions in brain and spine, presence of CLL cells confirmed by biopsy). He has been on ibrutinib for 13 months, which has successfully treated CLL blood levels but his mobility continues to worsen (walking with frame but with difficulty). MRI shows not much change in lesions. One treatment of methotrexate and rituximab was not repeated as there was no improvement. We feel ibrutinib is not doing the job in CNS. Would Venetoclax be more effective at crossing blood-brain barrier? Or any other regimen?
Ibrutinib does penetrate the central nervous system (CNS). It is unclear whether venetoclax does at this time. CNS involvement by CLL is extremely rare and the lack of response to ibrutinib should lead to a questioning of the diagnosis. It is important to remember that having CLL in the blood would lead to a biopsy of any body part showing some CLL. The important question is what else is there.
Does this report [link below] suggest 17p has a survival rate of 2 years?
The two year survival was 78%, which means 78% of patients were alive at two years and this was the control group, not those who received ibrutinib. There is also a tremendous impact upon whether ibrutinib is used as frontline or subsequent line of therapy, with the results being far superior for frontline. Additionally, venetoclax is a very effective agent available for patients with a deletion 17p. Given the above, I expect patients with deletion 17p to fare far better nowadays.
If peripheral blood is used to determine MRD post treatment, is it safe to assume that MRD using bone marrow will yield the same result? Alternatively, does MRD measured in bone marrow generally produce a higher level?
Bone marrow MRD is more sensitive than peripheral blood. A significant number of patients will have detectable bone marrow MRD but not blood.
I was diagnosed with CLL in 2005 and have been in “watch and wait” status. In May 2017, I found out that I had a thyroid issue. Thyroid tests have come back at normal levels. Since May, I have had 2 ultrasounds and needle biopsy. The last ultrasounds in November, 2017 indicated small change in the nodules on each side of the thyroid and irregular borders. Does CLL play a part in thyroid issue?
There is no association between CLL and thyroid disease. Thyroid disease is fairly common and we do find many nodules during the imaging done for CLL patients, but there is no association.
Should I avoid going to the opera during flu season? I have CLL in remission, but my white cell count is creeping up. Other blood work is good and I have no other symptoms.
It is not possible to advise you on going to the opera, but with proper precautions (handwashing, etc.) the risks should be minimal.
I have early CLL Raí stage 1. I’ve never needed treatment as we are in the “wait to treat” phase. Am I able to donate blood?
Patients with CLL, regardless of their clinical status are not eligible to donate blood.
I am scheduled for a bone marrow biopsy due to results of a flow cytometry test showing CLL cells. The abnormal cells made up only 5% of total. Can CLL cells detected by flow cytometry and not show in the bone marrow? What other possibilities are there in that case?
Low amounts of CLL cells in the peripheral blood could be a sign of what is called, monoclonal B lymphocytosis, which is sometimes a precursor to CLL, but not always. The low amounts of CLL cells in the blood could also be the result of the cells just not circulating and preferring to stay in the lymph nodes, spleen, and /or bone marrow. Differentiating between these two can often be done by physical exam (seeing if there is enlargement of the lymph nodes and spleen) and CBC.
After being on ibrutinib for 3 days, I developed a severe reaction: hives, mouth sores and joint pain. I was then put on 8 courses of rituximab and then I was on idelalisib for 6 months. Since the end of December I have had severe diarrhea, colitis and severe kidney damage. I am on the mend now, but am worried what the next step will be. Has this happened to any other patients?
Those reactions to ibrutinib are reported in small numbers of CLL patients. Additionally, the colitis is seen in patients who are on idelalisib long-term. Most patients do well for a period of time off therapy. When their disease relapses, there are other therapies available to them.
I have been taking ibrutinib for about 12 months. I have frequent muscle cramps in my hands, legs and rib area. My potassium and magnesium levels are normal. I’ve talked with representative manufacturer and they were unfamiliar with this. Thoughts?
Myalgias (muscle aches) are associated with ibrutinib. They tend to be more muscle aches, rather than cramps. It is important to make sure something else is not being missed.
Does CAR-T work for adult PLL patients?
CAR T cells could theoretically work on any malignancy that expresses the target that they are directed against. For most CAR T cells that would be CD19, which is present on all B cells and B cell malignancies, including some PLLs. We don’t have efficacy data specifically in PLL though.
I was first diagnosed with CLL 10 years ago with WBC 10. Over time, my WBC has risen to its current level of 25.6 and has remained throughout as Stage 0 to I patient. As of January 2018, the ultra-scan of my abdominal area is normal. I continue seeing a local oncologist every 6 months who recommends only observation. Should I get second opinion from a CLL specialist?
It is always advisable to obtain second opinions if you have any questions.
I am a very active 72 year old woman. On a routine cholesterol screening, my PCP informed me that my WBC was 13.6, ALC 6.6 with 48% lymphocytes. Everything else normal. My PCP informed me he never alerted me to my last two CBC’s which demonstrated Oct 2016 lymph at 10.62 ALC of 5.9; and last June of lymph 11.6 and ALC of 6.2. He said he feels we can make provisional diagnosis of CLL but I’m not convinced. I have no nodes, no spleen enlargement, no unexplained fatigue or fevers. Can you advise my next move?
It does sound as if you have an early stage process that is statistically CLL. It is worth confirming the diagnosis and assessing the different predictors of the disease course. You may not need treatment for a very long time, but it is better to have the diagnosis confirmed. I would suggest seeing a hematologist.
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 2018.