From the Journals

Despite limits, COVID vaccines protect CLL patients



While it’s well known that COVID-19 vaccines are less effective in patients with chronic lymphocytic leukemia (CLL) who take immunity-lowering drugs, a new study offers fresh insight into what’s happening inside the body. In these patients, the vaccines often don’t boost B cells, which produce antibodies, but they do strengthen T cells, potentially providing crucial protection against severe illness and death.

These findings don’t reveal whether the T-cell boost actually provides extra protection against COVID-19. Still, the study suggests that patients with CLL should be vaccinated no matter which medications they’re taking, coauthor and hematologist/oncologist Clemens-Martin Wendtner, MD, of the Munich (Germany) Clinic, said in an interview.

“Do not defer or pause treatment,” said Dr. Wendtner, whose study was published in Blood Advances.

Patients with CLL appear to have among the weakest responses to the COVID-19 vaccine among people with various types of blood cancer. A meta-analysis published in 2022 found that seropositivity rates following vaccination were just 51% in patients with CLL, compared with 80%-90% in those with acute leukemia and 76%-80% of those with myeloma.

“Usually, the response rate to vaccination among the nonimmunocompromised would be 95%,” Dr. Wendtner said.

Research has also suggested that patients treated with B-cell pathway inhibitors and anti-CD20 antibodies are especially likely to have poorer responses to COVID-19 vaccines, no surprise considering that their job is to dampen the immune system. But there’s an unanswered question, according to Dr. Wendtner: Does “just measuring B-cell response tell us everything about the immune response?”

The new prospective, single-institution study aims to answer that question in patients who each received two types of vaccines. Researchers compared peripheral blood mononuclear cell transcriptional response with antibody and T-cell response rates in 15 patients with CLL/small lymphocytic lymphoma following vaccination with both the Pfizer-BioNTech and AstraZeneca vaccines.

The average antibody response was limited. “Overall, 7/15 of patients failed to mount a humoral response even after three-dose vaccination,” the researchers reported. All of the patients were “heavily pretreated” with CLL medications such as venetoclax, an anti-CD20 monoclonal antibody.

By contrast, the T-cell response was much stronger: 80% of patients (12/15) had a robust response, a number that grew to 90% (14/15) after a booster. This response is “almost ideal” considering that the response in a nonimmunocompromised person would be about 99%, Dr. Wendtner said.

The study also revealed that vaccine responses were weaker in patients who took a combination of a Bruton tyrosine kinase inhibitor and venetoclax within a year.

Four patients developed COVID-19 infections with the Omicron variant about 6 months after vaccination. All had mild symptoms. A lone patient had a history of COVID-19 infection prior to vaccination.

The researchers noted that the study had several limitations, including its small size, its reliance on a single institution, and the differences in treatments and vaccination protocols among the patient population.

Broadly speaking, the study showed that “a vaccine is not in vain” in patients with CLL, “although the doctor might not detect an antibody response,” Dr. Wendtner said. He added that mixing vaccine types should provide more protection. Start with a viral vector vaccine followed by an mRNA vaccine or vice versa, he suggested.

In an interview, infectious disease physician Joshua A. Hill, MD, from Fred Hutchinson Cancer Center, Seattle, who wasn’t involved with the study, said it makes “important and interesting observations to reinforce other studies with similar findings.”

Specifically, Dr. Hill said, “despite the absence of a robust antibody response some of these patients who are on active treatment, patients can still generate robust cellular immune responses in the form of T-cell immunity. Our understanding is that having T cell immunity will provide important additional protection for developing severe disease, although is less easily tested.”

As for the best vaccination strategies, Dr. Hill said “patients should get vaccinated as soon as they are eligible, according to standard guidelines. If patients have not yet started therapy, they should get their indicated vaccines before starting treatment whenever possible.”

The German study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Bavarian State Ministry of Science and Art. Dr. Wendtner disclosed consultant fees from AstraZeneca and BioNTech, and another author disclosed consultant fees from AstraZeneca. The other authors reported no disclosures. Dr. Hill disclosed consultant fees from Moderna, Pfizer, and Gilead.

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