Historically, infection has been one of the most common causes of death in patients with CLL. Thus, risk of infection and the issue of vaccinations was an area of focus in CLL long before COVID-19. We typically will discuss vaccines at our first meeting with patients and then at regular intervals thereafter. We recommend that patients with CLL get vaccinated for pneumococcal pneumonia, shingles, hepatitis B, and seasonal influenza. However, we know that, despite all of these immunizations, patients with CLL will continue to have a greater risk from infections due to factors that are both disease and treatment related. 

Regarding COVID-19 specifically, we are beginning to learn more about the responses to available vaccines in patients with CLL. A recent European Research Initiative on CLL study published by Herishanu and colleagues analyzed anti–SARS-CoV-2 antibody titers 2 to 3 weeks after the administration of the second dose of the BNT162b2 mRNA COVID-19 vaccine. Overall, the antibody response rate was low among 167 patients with CLL (ie, approximately 40%), which is comparable to the rates of response to other vaccines, such as the conjugate pneumococcal vaccine. Patients who were receiving CLL treatment had the worst responses. For instance, responses were reported in only 16% and 14% of patients taking Bruton tyrosine kinase inhibitors or venetoclax ± anti-CD20 antibodies, respectively. Further, none of the patients exposed to anti-CD20 antibodies in the 12 months preceding vaccination had a positive serological response to the COVID-19 vaccine. Those who were on observation also experienced reduced responses and lower antibody titers after vaccination compared with healthy individuals. The patients who responded best to vaccination were those whose CLL was in remission after treatment, with researchers reporting a serologic response of approximately 79% in this group.

It is important to note that antibody response rates do not give a complete representation of protection. Herishanu et al noted that antibody titers are dramatically lower in patients with CLL compared with the general population, even among those who did respond by making anti–SARS-CoV-2 antibodies. Individuals with CLL are much less likely to have the higher levels of protection from vaccines that are observed in the general population. 

Thus, one approach is for patients to get vaccinated but then to also continue taking precautions as if they were unvaccinated. COVID-19 vaccines may offer some benefits by reducing the severity of illness and the risk of hospitalization, but we are still recommending that patients wear masks and socially distance. The emergence of new variants such as the Delta variant tells us that COVID-19 remains a moving target. However, the variants have not changed our overall approach, and I continue to recommend the vaccine to my patients, including a third dose of the mRNA vaccine, as recently recommended by the Centers for Disease Control and Prevention for patients with suppressed immune systems.