We know that patients with CLL have impairments of both their adaptive and their innate immune systems. In general, this degree of impairment tends to worsen over time. Notably, infections are one of the greatest causes of morbidity and mortality in these patients. We have known for some time that patients with CLL do not respond well to vaccines, and, despite a variety of attempts over the years to improve vaccine response in these individuals, none of these efforts have been very productive.

It is important that patients with CLL are vaccinated early in the course of disease, preferably before they start any treatment, and then subsequently at regular intervals according to the guidelines. Early vaccination against pneumococcus, for example, is important in those with CLL, and the vaccination guidelines for immunosuppressed populations—not immunocompetent populations—should be followed (eg, vaccination with both the pneumococcal conjugate vaccine PCV13 and the pneumococcal polysaccharide vaccine PPSV23 is indicated). Vaccinating early against shingles is also important to maximize the likelihood of protection. Shingles is a common problem among patients with CLL, and it can be quite debilitating, so any protection that we can offer is helpful.

Generally, intravenous immunoglobulin (IVIG) is not considered in patients with CLL unless they have hypogammaglobulinemia and repeated lung and/or sinus infections. It is important that patients meet this threshold for IVIG for several reasons. IVIG is cumbersome to administer, it must be given serially because the effects wane over time, and it does not provide much benefit against seasonal viral respiratory infections, although it may be helpful in patients with secondary bacterial infections.

COVID-19 is a major problem in this patient population, as those with CLL have a high risk of developing complications from COVID-19. We recommend that all patients with CLL get vaccinated and boosted against COVID-19. Although individuals with CLL are unlikely to get the same level of protection against COVID-19 with vaccination as healthy persons, some protection is better than no protection. I try to impress on patients that they are still at risk despite receiving the vaccine. 

Regarding treatment options and infection risk, anti-CD20 antibody therapy raises some concerns in that it achieves profound B-cell depletion, which may undermine protective immune responses. Additionally, one needs to come in for the infusion, and there is the perceived risk of contracting a nosocomial infection with frequent health care contacts. However, all therapies, including Bruton tyrosine kinase inhibitors, impair immune responses to COVID-19 vaccines. Conversely, patients who received time-limited therapy prior to the start of the COVID-19 pandemic and achieved a deep remission had the advantage of being off therapy during the pandemic and not having to come in for infusions.