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Over the past 14 months, the degree of suffering that health care providers have watched patients and families go through as a consequence of the SARS-CoV-2 pandemic has been overwhelming. This extends from those who get an active infection with the virus (COVID-19 syndrome) to those who remain in deep isolation to prevent themselves from getting it. Many patients have commented how life essentially has come to a near stop during this time of isolation due to not being able to see their children, grandchildren, family, and friends. Additionally, patients with jobs requiring contact with others have not been able to perform effectively in their work environment. Since December 2020, we have been excited about the potential of several new vaccines that clearly protect young healthy individuals from severe COVID-19 but have a more varied efficacy in older patients and those who are immunocompromised.
Recommendations have come forth just recently from the US Center for Disease Control (CDC) that liberalize recommendations for those who are vaccinated. How do these apply to CLL patients who have been vaccinated? The truth is we do not know, as there are little data available that really look at CLL protection from vaccine dosing as it relates to preventing serious COVID-19 syndrome. This is very similar to much else in the SARS-CoV-2 pandemic where we have been forced as physicians to extrapolate from our opinion, knowledge of other vaccines, and integration of risk to benefit for our patients.
With this in mind, I would like to share my approach to discussing the vaccine with patients as it relates to the most common questions I get asked in the clinic. These 12 questions are probably the most common. Virtually everything here is my own opinion and other physicians may very well disagree. For this, I would say virtually all the questions have little data to support any opinion. So truthfully, the right answer is not known-it is just opinion.
1. As a CLL patient, should I get the COVID-19 vaccine?
Yes, one should get the COVID-19 vaccine. Unless there are extenuating circumstances to your CLL history or past medical history that would prohibit this, or if you have had a very severe reaction to the first vaccine dose (MODERNA or Pfizer).
2. If I am currently in treatment for CLL, should the COVID-19 vaccination be delayed, and should my treatment be held for a period of time?
We do not know the answer to this. In general, I recommend patients get the COVID-19 vaccine as soon as possible. I also do not stop therapy for CLL to administer the vaccine. This is particularly true for BTKi where discontinuation may result in a tumor flare (painful enlargement of lymph nodes). While it is true that BTKi such as ibrutinib and acalabrutinib may decrease the vaccine response, they also reverse immune suppression which may increase the ability of CLL patients to gain some benefit to the vaccine. Until a rigorous study can be done, we will not know the answer to this question. Also, it should be noted that we have observed patients on long-term ibrutinib or acalabrutinib that have had robust antibody responses to the COVID-19 vaccines.
3. If I am getting ready to start treatment for my CLL, should I delay the start date in order to get vaccinated first?
We do not know the answer to this question, but in general, it has been my approach to delay the treatment start date until the patient can become vaccinated, particularly if the CLL treatment is going to involve something that depletes normal B-cells. Examples of this would be venetoclax, CD20 antibodies (such as rituximab or obinutuzumab), and chemotherapeutic agents. Personally, I would even delay starting treatment for those who are starting ibrutinib or acalabrutinib.
4. Is there a better vaccine for CLL patients to receive?
We also do not know the answer to this but inference to the populations tested would suggest the mRNA vaccines (Moderna then Pfizer) could possibly be better for cancer patients. That being said, taking the one that you have access to is the approach that should be taken. In the future, it may be possible to receive another vaccine class if you do not demonstrate a vaccine response to what you previously received.
5. Should I have my spike antibody or T-cell response tested after receiving the vaccine?
There is not a right or wrong thing to do, and a conservative approach would be to say that no monitoring should be done as this is the approach we take for flu, shingles, and pneumococcal pneumonia vaccine shots. This would be one example of a correct answer. However, SARS-CoV-2 viral infection is different because it can carry a high risk of infection in those not immune to it, as well as a high mortality rate. It requires those who want to avoid becoming infected with it to live like hermits. For someone who is in their 70’s and has grandchildren and family they enjoy being around, it significantly impacts their mental well-being to remain isolated for such a long period of time. For those who must work in the service or teaching industries, it can affect their livelihood and ability to remain financially solvent. Knowing if the vaccine has provided some level of protection for these individuals allows them to at least have a little more information to extrapolate if they have any amount of immunity to SARS-CoV-2, or if they remain closer to their pre-vaccine state. This is where the spike antibody tests can help. In my practice, we have been using them. I have been recommending the spike IgG protein (RBD site-specific antibody) test that when detected indicates there has been some level of benefit derived from the vaccine. Some labs report out titers but the relevance of these to CLL patients remains uncertain. For patients where I suspect they may have previously had COVID-19 syndrome, I also test for the nucleocapsid (N) IgG.
6. If someone receives the vaccine and has a detectable spike IgG protein site-specific antibody, what does it mean?
At present we do not know the answer to this for CLL patients. In my own opinion, this tells me the immune system has had some response to the vaccine, and perhaps there is some protection. I generally counsel my patients by saying that continuing complete isolation and other precautions is the absolute safest for them. But following the CDC guidelines, post-vaccination is also reasonable with some important caveats. I still recommend that my CLL patients avoid going inside restaurants, bars, and attending large events where SARS-CoV-2 infection could more easily occur. I also encourage traveling by car (versus air) whenever possible. In my own personal opinion, when a patient has a positive spike protein antibody test after vaccination, there is some justification for loosening up on some of the restrictions, particularly when it comes to important things such as seeing family members and grandchildren. When it comes to working, one must consider balancing the risks versus the benefits, but with extra precautions. Personally, I feel comfortable letting my patients go back to work if they have had a positive vaccine response. I would like to emphasize that this is my own personal approach. It comes with essentially no data, but rather inference from our past experiences with infectious pathogens.
7. If someone receives the vaccine and does not have an IgG spike protein RBD site-specific antibody, what does that mean?
There are no data on this at the present time for CLL patients. In my own opinion, this tells me the immune system may still have had some response to the vaccine (via T-cells), but the humoral response (B-cells that produce antibodies) did not occur. For a patient who does not have an IgG- spike protein antibody response, there might be a higher risk of loosening up SARS-CoV-2 than the patient who has an antibody response. In my own practice, I would advise this person to be extremely cautious and carefully examine their willingness to take risks, particularly when a high potential exists for exposure to the virus. Unfortunately, we are going to be living with SARS-CoV-2 for some time to come. So, while the continuation of safety precautions is still very critical for CLL patients, finding the right balance individually is also important.
8. If I have a T-cell response to the vaccine, what does that mean?
For CLL and non-CLL patients, the full protective benefit of T-cell response against preventing COVID-19 syndrome is not yet known. There is a commercial test available that examines this, but it is not yet something we do in our practice. However, it remains an important area of research for which we hope more information will be forthcoming very soon.
9. For CLL patients who do not have a vaccine response as measured by detectable antibodies, is there hope of other treatments that might provide some level of protection for us coming in the future?
There absolutely is hope. There are a number of man-made neutralizing antibodies that might have the same protective effect as the COVID-19 vaccines. These are all currently in clinical trials and may be available soon. Additionally, there is the possibility of adjuvants (which is a substance that enhances the body’s immune response to an antigen). These adjuvants would work by enhancing vaccine response and may improve protection. Finally, as more research occurs, it may become apparent that T-cells specific to the SARS-CoV-2 virus may provide some protection against COVID-19.
10. Why is there so much confusing information out there from various healthcare providers and also on the internet related to vaccine response in CLL patients?
At this point, there has been very little studied, and as a result, very little is known. But what we do know is that CLL patients are at higher risk for serious COVID-19 syndrome and also, they do not respond as well as the general population to the available vaccines. For everything else it is similar to going to the horse race and gathering information about past performance, looking at the horse‘s shape and condition and last run, the current conditions (is it raining or dry outside) and then making a bet on who Is going to win. If you are conservative and don’t want to lose your money, then the best thing to do is simply not to bet. During a pandemic, this conservative approach would equate to following strict precautions and isolating similar to what you have done before the vaccines were ever available. If you use all the information that is currently available to determine your level of risk (such as your antibody response and seeing low-risk people only), then you may choose to move forward with a more conservative approach. However, f you are a bit more of a risk-taker, you may simply take the vaccine and follow the CDC post-vaccine guidelines and choose a less conservative approach. There is no right answer here but there are several choices that can be made based upon an individual’s circumstances and willingness to take risks.
11. Should I seek multiple opinions about what to do related to COVID-19, vaccines, etc., from different doctors?
In my own humble opinion, the lack of data will result in many different opinions that could be confusing. There is not a right or wrong here but getting to a point of being comfortable with what you decide to do after receiving the vaccine is important. If getting an extra opinion helps you become more comfortable with your decision, it may be worth doing. We are going to be in this for the long hall, so being at peace with your decision is important.
12. What can I do to help with the lack of information related to vaccine protection in patients with CLL?
Several studies are being sponsored by institutions, organizations (i.e., Leukemia and Lymphoma Society), and companies addressing many of these questions. Participating in research studies that are well designed and conducted will lead to getting the answers we need in the future. I strongly encourage this!
I wish to thank Dr. Brian Koffman for asking me to write this opinion piece and want to thank the many individuals who have visited me for a second opinion or been under my care at Ohio State over the past two decades. This time has allowed the CLL program to grow with four wonderful doctors (Drs. Woyach, Rogers, Kitai, and Bhat) who care for patients with CLL. An opportunity to grow another medical center has come up and I will be transitioning to the University of Cincinnati on July 1st of this year. At the University of Cincinnati, I will be continuing my consultative and active practice caring for CLL patients. My wife Laura and myself are very excited about this transition to Cincinnati. I look forward to working with Dr. Koffman through the CLL Society (by both donating and providing my professional time) while continuing to see patients, performing clinical research, and identifying new drugs for the treatment of CLL at the University of Cincinnati to support the CLL community.
John C. Byrd, M.D.
Please remember, CLL Society cannot provide medical advice. All suggestions written in this opinion piece should be reviewed with the healthcare team managing your CLL care.