CLL Monthly MinutesLeukemia

Protecting Patients with CLL from COVID-19

A recent study provides some of the first data on COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia.
Web Exclusives – September 20, 2021

Chronic lymphocytic leukemia (CLL) is a cancer of the blood and bone marrow that can leave patients at risk of developing both bacterial and viral infections.1,2 With the 2019 emergence of the novel coronavirus SARS-CoV-2—the cause of COVID-19—questions arose about the impact of this new virus on patients with CLL, and how best to protect them.

More than a year into the pandemic, it is now generally understood that patients with CLL are at higher risk of contracting severe COVID-19 and are at higher risk of mortality from the disease.2,3 Data from 2 large studies conducted across Europe, South America, and the United States found that 80% to 90% of patients with CLL and COVID-19 presented to the hospital with severe disease, and about one-third died of their infection.3 Interestingly, these 2 studies differed on 1 key finding: 1 of the studies suggested that patients receiving treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may less likely be hospitalized for COVID-19, whereas the other study showed no such protective effect.3

Although other studies have yet to confirm that BTK inhibitors can minimize the complications of COVID-19, most doctors are continuing their patients on these treatments.2,3 On the other hand, there is general agreement to stop CLL treatments like traditional chemotherapy, monoclonal antibodies, and the BCL-2 inhibitor venetoclax when a patient is diagnosed with COVID-19.2,3

Another important question for patients with CLL is regarding the effectiveness of the authorized COVID-19 vaccines. Previous studies have shown that flu vaccines and hepatitis B vaccines may be less effective in patients with CLL who are treated with BTK inhibitors.1,4

In clinical trials, the 2 COVID-19 vaccines based on mRNA technology (one from Pfizer-BioNTech and the other from Moderna) have shown 94% to 95% efficacy in preventing symptomatic infection, regardless of the individual’s age.1 However, these trials did not include patients with hematologic cancers like CLL.1

In a recent study, investigators in Israel evaluated the effectiveness of 2 doses of the Pfizer-BioNTech COVID-19 vaccine in 167 patients with CLL.1 Of all the patients with CLL who received the vaccination, only 66 (39.5%) were found to have antibodies to the virus that causes COVID-19.1 When the investigators compared 52 patients with CLL with 52 healthy subjects who were matched for age and sex, they found that all of the healthy individuals showed a vaccine response, compared with only about half (52%) of the patients with CLL.1

Looking more closely at the data, the investigators found that vaccine response was highest (79%) in patients who were in clinical remission after receiving CLL treatment.1 Patients diagnosed with CLL who had not been treated had a response rate of 55%, whereas those undergoing treatment at the time of vaccination only had a response of 16%.1 Most patients on treatment were receiving either a BTK inhibitor or venetoclax in combination with an anti-CD20 antibody.1 Both treatment regimens were associated with low vaccine response: 16% for those on BTK inhibitors and approximately 14% for those on the venetoclax regimen.1 The researchers concluded that a combination of disease activity and treatment-related factors were responsible for low vaccine response in patients undergoing treatment in CLL; however, they did not propose an explanation for the specific biological causes of this difference.1

Despite these data, doctors still recommend that patients with CLL be vaccinated with the first available vaccine.3 To best protect themselves, vaccinated patients should also continue to adhere to masking and social distancing practices and encourage vaccination of their close contacts.1 Future studies will evaluate booster vaccinations in this vulnerable population.1


  1. Herishanu Y, Avivi I, Aharon A, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood. 2021;137:3165-3173.
  2. American Society of Hematology. COVID-19 and CLL: frequently asked questions. February 2, 2021. Accessed August 6, 2021.
  3. Minerd J. Clinical challenges: chronic lymphocytic leukemia and COVID-19 – BTK inhibitors may have a protective effect; ASH offers guidance. June 14, 2021. Accessed August 6, 2021.
  4. Shadman M, Ujjani C. Vaccinations in CLL: implications for COVID-19. Blood. 2021;137:144-146.

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Last modified: September 20, 2021

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