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CLL Answers Now: Q&A With Dr. Kerry Rogers and Dr. John Allan

CLL Answers Now: Q&A With Dr. Kerry Rogers and Dr. John Allan
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Published on May 21, 2021

CLL FAQs Answered by the Experts

During a recent Patient Power live program, two experts in chronic lymphocytic leukemia (CLL) discussed treatment advances, therapy combinations, and the latest clinical trials. Kerry Rogers, MD, is an Assistant Professor in the Division of Hematology at The Ohio State University and John Allan, MD, is an Assistant Professor of Medicine at Weill Cornell Medicine.

Here are some of the questions from patients that they didn’t have time to answer during the program.

Q: Have you ever seen a case of spontaneous remission of CLL?

Dr. Allan: I have not seen a case of spontaneous remission. Some lymphomas have reported spontaneous remissions, but with CLL this would be unlikely to occur.

Q: Please explain LOXO-305.

Dr. Allan: LOXO-305 is a non-covalently bound reversible inhibitor, meaning that it is not bound permanently to Bruton tyrosine kinase (BTK) once it interacts. All current BTK inhibitors (BTKis) that are now available bind permanently and shut down the protein function. Mutations in BTK prevent this permanent binding, thus making the inhibitor ineffective. LOXO-305 overcomes this by having long pharmacokinetic (PK) activity and being able to interact and shut off BTK signaling despite a lack of permanent binding.

Q: If you are tested by multiple flow tests with minimal residual disease (MRD) results, is it possible to consider coming off a BTK inhibitor?

Dr. Allan: That presumably can be considered since we currently stop patients who are MRD negative and treated with venetoclax. With that said, the current standard of care is continual therapy with a BTKi, and any deviation from that approach should be discussed with your physician to ensure that you understand possible risks of stopping treatment and the lack of data to understand the potential outcomes of that decision.

Q: If someone is told that they have a 17p deletion, does that mean that more than 25 percent of their CLL cells have a 17p deletion? In general, how quickly would someone with 20 percent of their CLL cells with a 17p deletion become classified as del17p?

Dr. Allan: The thresholds for del17p being classified as “real” on a test vary but can be as low as 7 percent to 10 percent. Data suggests that patients with del17p percentages less than 20 percent behave and respond similarly to patients that are del17p negative. However, if the fluorescence in situ hybridization (FISH) assay picks it up, I would still consider your disease to be del17p. On a positive note, if you utilize targeted therapies, current evidence suggests that you will likely have an excellent outcome.

Q: Do BTK drugs do well for those us who have 17p deletion and are IGHV unmutated?

Dr. Allan: The BTKis are great drugs for patients with high-risk features with del17p and unmutated IGHV. It would be recommended to avoid chemotherapy, however.

Q: Does an enlarged spleen alone indicate a need for treatment?

Dr. Allan: It depends on how large. If the spleen is mildly enlarged and you are asymptomatic, it can be monitored. In general, progressive or symptomatic splenomegaly, or splenomegaly greater than 6 cm below the costal margin, are indications for treatment.

Q: I am del17p and was diagnosed in November 2020. My hemoglobin, red blood cell count (RBC), and white blood cell count (WBC) count are not too bad. I have daily fatigue and redness/purplish discoloration of three toes. My oncologist is very concerned the toes are collecting cancerous cells. I’m doing a biopsy and trunk CT scan. Have you ever had a patient with toe issues?

Dr. Allan: Sometimes CLL can be associated with cryoglobulinemia, which may be causing a Raynaud-like phenomena and vasospasm of your toes. It is an uncommon symptom, but potentially those changes could be caused by the CLL. I believe the workup your physician is pursuing is appropriate.

Q: I am being treated with obinutuzumab and venetoclax, with immune globulin (IgG) levels that are below 500. Is this a permanent condition or might I slowly recover? Also, can I do anything (besides IgG infusions, which I have not gotten yet)? I'm not symptomatic.

Dr. Rogers: Sometimes antibody levels increase after treatment as the immune system recovers, but most of the time they do not, or if they do, they do not return to normal levels since decreased IgG levels are part of having CLL. There is nothing I know of, aside from antibody (IVIG) infusions, that can increase this level.

Q: I am on active treatment for CLL, taking both obinutuzumab and venetoclax. I’ve had the Pfizer COVID-19 vaccine with no spike protein response. Is it true that if you’re on a monoclonal antibody (MAB) treatment that will negate the COVID-19 vaccine response? Should I retake the vaccine once I’ve been off the MABs for 6 months? What blood labs would be a good indicator of when I should consider retaking the vaccine?

Dr. Rogers: Yes, it is true that anti-CD20 monoclonal antibodies such as obinutuzumab and rituximab decrease the body’s ability to make antibody responses. We have seen this with these medications when they are used for CLL and to treat other conditions. These drugs (obinutuzumab and rituximab) target and destroy the B-cells that make antibodies as a main mechanism of action. That information comes from studies with vaccines that were available prior to the COVID-19 pandemic and seems to be holding true with the COVID-19 vaccines as well. In people taking these for autoimmune disease who do not have CLL, there is a better chance of making antibodies if vaccinated 6 months after treatment. I am not at all sure this applies to people with CLL and to those who took venetoclax with obinutuzumab, as venetoclax also decreases immune responses. I am not aware of any labs that would help determine when your body might have a better chance of responding. Currently, there is no plan to revaccinate people without an antibody response, but I expect this will become an option as we gain more experience with the vaccines.

Q: Can T cell immune response be measured, and how important is this?

Dr. Rogers: It can be measured as a research test. I am not aware of any tests for this that can be reported to patients as a regular lab test. We do not currently know how important T cell immune responses are for COVID-19 vaccination and infection.

Q: I'm treatment-naive, stage 0 and had a negative response to the COVID-19 vaccine. I also had a reaction after the second shot. I'm confused about why I had no antibodies.

Dr. Rogers: The reaction means you had some type of immune response to the vaccine, but you did not have an antibody response. Many people with CLL do not have antibody responses to the vaccine, but your immune system is more than just antibodies. Some other part of your immune system responded to the vaccine in this case.

Q: Does ibrutinib have an impact on COVID-19 vaccine effectiveness?

Dr. Rogers: Great question. Probably, but in exactly what ways we do not know for sure at this time.

Q: Does stimulating the immune system with vaccines trigger the growth of white blood cells?

Dr. Rogers: This is a broad question as there are many types of white blood cells. I would expect vaccines to cause the white blood cells that are lymphocytes responding to the vaccine antigens to grow. I would not expect it to increase other types of white blood cells. In most cases, it should not trigger a large growth of white blood cells and any increase in white blood cell growth after vaccination will decrease again in a week or two. Think of it like infections, it stimulates the immune system and responding immune cells can grow, but then once the response is over things go back to normal. You may have seen white blood cell counts increase in people with infections and then they go back to normal the next week once the person is better.

Q: Why would chimeric antigen receptor (CAR) T-cell treatment require premedication immune suppression if self-T-cells are used?

Dr. Rogers: This is a complex question, but you can think of it like this: If your body already has enough immune cells it will not have space for the CAR T ones that are infused to grow and thrive. The chemotherapy pre-treatment or “conditioning” is to make room in the immune system to have the cells back.

Q: Does it make sense with CLL (IGVH mutation and 13q deletion) to use just venetoclax without obinutuzumab? My husband had extreme fatigue (not able to get out of bed) after his first obinutuzumab infusion. Now the doctor wants to stop obinutuzumab and just start venetoclax. He is 60 years old and was in very good shape prior to this. He has 95 percent bone marrow infiltration and no huge lymph nodes.

Dr. Rogers: It is unclear how important obinutuzumab really is in the venetoclax-obinutuzumab treatment regimen. Venetoclax does work well as a single agent and in someone with severe side effects from obinutuzumab, it may not be worth getting more obinutuzumab treatment.

Q: I was diagnosed with CLL in June 2020, and I recently had an all-normal complete blood cell count (CBC). This was after I received both Pfizer COVID-19 vaccine doses. Do you think there is any correlation to the vaccine or is it just because I have improved my already very healthy diet and exercise even more?

Dr. Rogers: Great question. I doubt it is vaccine-related because I cannot think why the vaccine would improve the CLL. I have seen this happen before in a few people. I’m not sure why this happened in your case, but that is great!

Q: Omitting BTK inhibitor resistance issues, what is the relative efficacy of non-covalent vs. covalent BTK inhibitors?

Dr. Rogers: No idea… yet. We need more experience with the non-covalent BTK inhibitors to be able to answer this question. We hope to find out this answer in the coming years.

You can view the original CLL event with Dr. Rogers and Dr. Allan here: https://patientpower.info/cll-the-next-generation/.

Support for this series has been provided by AbbVie Inc. and Genentech, Inc. Patient Power maintains complete editorial control and is solely responsible for program content.


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