Many of you already know CLL expert Dr. Rick Furman, Director of the CLL Research Center at Weill Cornell Medicine in New York City, who generously answers your questions for our Ask the Doctor feature.
With his permission, I am republishing a great email that Dr. Furman sent off in response to the many questions he has been receiving from chronic lymphocytic leukemia patients concerning the SARS-CoV-2 vaccines to fend off COVID-19.
This originally appeared in the CLL/SLL io group on Dec. 31, 2020.
I have been inundated with emails regarding questions of whether to take the vaccines or not. I really do believe that the vaccines offer the best means currently for helping reduce the risks of becoming severely ill from COVID-19. I hope this post will help allay fears.
- While these vaccines have been developed and approved quicker than any vaccine in history, and have used novel technologies, we do not have any reason at this time to question their safety. The RNA vaccine technology (more later) has been used for years in animal vaccines, just not human vaccines, and are extremely well studied. They really represent a major step forward in generating vaccines rapidly. They really are only limited by the need for cold temperatures for storage.
- While the timelines for these vaccines have been very short, these vaccines are studied in large number of patients. (Pfizer: 40,000 in total in the pivotal trial: 20,000 vaccine vs 20,000 placebo; Moderna: 30,000 in total in the pivotal trial: 15,000 vaccine vs 15,000 placebo.) Most of our oncology drugs are approved using studies of 150-300 patients.
- The RNA vaccines use RNA encapsulated in a lipid vesicle to deliver it to cells where it is taken up and transcribed (processed) like normal RNA into a protein that is placed on the surface of the cell for the immune system to see and recognized as foreign. This really replicates what the virus itself does. There is no means for the RNA to be changed into DNA, make it into the nucleus, or enter the cell’s normal DNA. The Pfizer/BioNTech and Moderna vaccines are RNA vaccines.
- The AstraZeneca/Oxford vaccine, approved this past week in the United Kingdom is different in that it uses a replication deficient virus. The virus infects cells and places its immunogenic proteins on the surface of cells for the immune system to react to. Even though this is not a killed virus vaccine, this vaccine should still be safe from a CLL perspective. The one issue with the AstraZeneca/Oxford vaccine is that there were some errors in the conduct of the clinical trial which might make the data suspect. One group of patients received a half-dose of vaccine. Interesting, these patients seem to be better protected when looking at the numbers. There are several theoretical reasons why this might occur, but it is counterintuitive. There were some differences in spacing the vaccine doses, which may also explain some of the benefit. The efficacy in the majority of the patients is lower, approximately 60%. What we are missing are the data with statistics to assess whether these are meaningful differences or possibly due to chance.
- We have no reason to believe there is any advantage of the Pfizer/BioNTech or the Moderna vaccine over the other. Both vaccines did numerically very close (which is very reassuring) and none of the differences in outcomes is statistically meaningful.
- We currently do not have efficacy or safety data for these vaccines in patients with CLL. With this being said, we do not have any reason to expect the safety to be different in patients with CLL. While we do have theoretical reasons for why the vaccine might be less effective, and therefore alter a risk-benefit assessment, these vaccines are very immunogenic and will hopefully be equally efficacious in patients with CLL. We also know how dangerous COVID-19 infection is and therefore any steps that could be taken to lessen the risk of morbidity or mortality is critical.
- We should also remember that the vaccines were shown to reduce illness, but this does not mean that patients cannot get infected and still be contagious. The vaccines may lessen the duration of viral shedding, and therefore risk of spreading the virus, but may not limit it altogether. As such, people previously infected and people who have been vaccinated, still need to follow all of the safety protocols until “masks off” if declared.
- Many patients are on different treatments during this period. We don’t know whether any of these treatments will impair the immune response to the COVID-19 vaccine. While we have some anecdotal evidence of BTK inhibitors helping prevent severe COVID-19 illness, the clinical trial data are still emerging. The acalabrutinib trial in COVID-19 (non-CLL patients) did not show a benefit, but there were some issues with that trial that might not make it generalizable to everyone. I suspect that BTK inhibitors do help and have been continuing my patients on them. With regard to the vaccine, any temporary interruption will likely not be sufficient to make a difference and I would recommend just continuing the inhibitor. I am also recommending the same for the PI3K inhibitors and venetoclax. Anti-CD20 monoclonal antibodies would be different, and it might make sense to defer vaccination until after therapy is completed if there is an option.
I hope this helps everyone. I do encourage everyone given an opportunity to accept the vaccine. Additionally, I do encourage everyone to still practice mask wearing and safety protocols.
Happy and Healthy New Year to everyone. I hope we will be able to resume some normalcy this coming year.
Rick Furman, MD
I would add that Dr. Furman has also more recently commented that IVIG is unlikely to interfere with the vaccine’s efficacy.
Thank you, Dr. Furman, for a clear and helpful review of what we know and don’t know about SARS-CoV-2 vaccines for CLL patients.
The data are changing fast. Trials will be opening soon to examine if our response to the vaccine are muted or not. CLL Society will link to both the opportunity to participate and later the results as they become available.
Stay strong, stay safe.
We are all in this together
Brian Koffman, MDCM (retired)
Co-founder, Chief Medical Officer, and Executive VP, CLL Society