Blood Cancers Diminish Response to COVID-19 Vaccine

July 2021

“Recent research suggests that patients with blood cancer may have a diminished immune response to COVID-19 vaccination. In a pair of studies, patients with chronic lymphocytic leukemia (CLL) and multiple myeloma were less likely to produce SARS-CoV-2 antibodies than healthy people—and responses were particularly low in certain patients, such as those actively receiving treatment.

Studies have shown that patients with blood cancers are more susceptible to severe COVID-19 infection than patients with solid cancers or healthy people, likely due to the immunosuppressive nature of their disease and/or treatments. However, researchers wanted to know whether immunosuppression would also cause patients with blood cancers to have a weakened immune response to the COVID-19 vaccines being given worldwide.

Yair Herishanu, MD, of Tel Aviv University in Israel, and his team explored how patients with CLL responded to the Pfizer/BioNTech COVID-19 vaccine BNT162b2(Blood 2021 Apr 16 [Epub ahead of print]). They found that 39.5% of 167 patients were positive for SARS-CoV-2S antibodies—primarily consisting of IgG antibodies—after their second vaccine. In a comparison of 52 patients with CLL and 52 sex- and age-matched healthy controls, antibody responses were 52% and 100%, respectively. Patients in clinical remission after treatment had the highest response rate of 79.2%, followed by 55.2% in newly diagnosed patients who hadn’t received treatment. The lowest response rates were seen in patients treated with BTK inhibitors (16%) or the BCL2 inhibitor venetoclax (Venclexta; Genentech/AbbVie) with or without an anti-CD20 agent (13.6%). No responses were seen in patients treated with an anti-CD20 drug in the year before vaccination.

“The take-home message is that the antibody response to the messenger RNA COVID vaccine is impaired in CLL patients,” Herishanu says, and this impairment is more pronounced in patients on certain therapies. He and his team will continue to follow patients to see how quickly their antibody levels decrease, and how many of them develop COVID-19 infections.

“This is a very important paper—it’s the first robust dataset I’ve seen for vaccine efficacy in CLL patients,” says Matthew Davids, MD, MMSc, of Dana-Farber Cancer Institute in Boston, MA, who was not involved in the study. “I think it gives us a sense initially of which patients may be more likely to respond.” For him, the results suggest that clinicians may want to consider whether CLL treatment can be safely delayed until after patients have been vaccinated—especially for those who will receive an anti-CD20 agent.

Now, he wants to know what level of antibody response is protective in patients with CLL. Another key question, he says, is whether patients mount any other type of immune response—for example, a T-cell response—that provides protection. Davids is currently collaborating with researchers at the University of Washington and the Fred Hutchinson Cancer Research Center, both in Seattle, on a similar U.S. study.

In the UK, Kevin Boyd, PhD, of the Royal Marsden Hospital and the Institute of Cancer Research, both in London, and his colleagues examined antibody responses in patients with multiple myeloma after the first dose of BNT162b2 or the Oxford/AstraZeneca vaccine AZD1222 (Lancet Haematol 2021 Apr 19 [EPub ahead of print]). Overall, 56% of 92 patients tested positive for SARS-CoV-2 IgG antibodies, a percentage that rose to 70% when patients were tested for total SARS-CoV-2 antibodies. In contrast, 99% of 177 vaccinated hospital staff were positive for SARS-CoV-2 IgG antibodies. Antibody response rates were even lower in patients with active disease, those with immunoparesis, and those receiving any treatment for cancer.

“Although we’ve defined that the majority of patients with multiple myeloma have some response, what we’ve also defined is that patients respond less well to vaccines than the general population,” Boyd says. He adds, however, that “whether that genuinely means they’re not protected at all is a great unknown” until researchers can assess their risk of contracting COVID-19. Boyd and his team are working on a larger study that will offer additional insight into vaccine responses in patients receiving specific treatments. Longevity of response should also be studied, he says, as it will likely dictate whether patients will need more frequent vaccine boosters than the general population.

According to Suzanne Lentzsch, MD, PhD, of the Columbia University Herbert Irving Comprehensive Cancer Center in New York, NY, the study provides useful information about which patients with multiple myeloma may not respond to the vaccine—and draws similar conclusions as a small study on neutralizing antibody response in patients with multiple myeloma (Blood 2021 Apr 16 [EPub ahead of print]). Lentzsch, who was not involved in either study, is eager for larger trials that explore the full extent of the immune response in patients with multiple myeloma and other blood cancers. Real-world data on the rate and severity of COVID-19 infections in vaccinated patients with hematologic malignancies, she says, will also be telling.

In the meantime, “the message for patients is to get the vaccination, but make sure that you are aware that you might not build up antibodies,” Lentzsch says, adding that family members and friends must also be vaccinated.

“I’m telling my patients to be careful: to continue practicing social distancing, wearing masks, handwashing,” Davids agrees. “You really can’t assume you’re protected even if you’re ‘fully vaccinated.’” –Catherine Caruso

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