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In multiple myeloma patients unable to mount a sufficient antibody response following COVID-19 vaccination, roughly one-third also failed to mount T-cell responses, an important and durable source of protection, researchers determined.

Among 26 myeloma patients who were seropositive after COVID vaccination, 25 (96%) had a CD4+ T-cell response versus just six of 17 seronegative patients (35%), reported Samir Parekh, MBBS, and colleagues of the Icahn School of Medicine at Mount Sinai in New York City.

In addition, fewer patients on active anti-B-cell maturation antigen (BCMA) bispecific therapy or anti-CD38 antibody therapy mounted SARS-CoV-2-specific CD4+ T-cell responses compared with patients on other therapeutics or anti-BCMA CAR T-cell therapy, they noted in .

Because vaccination failed to induce anti-SARS-CoV-2 spike (anti-S) antibody responses in seronegative patients, Parekh and colleagues also investigated whether the lack of response reflected an inability of the vaccines to induce spike-reactive B cells.

They found that spike-reactive B cells were detected in almost all seropositive patients (again in 96%), as well as in all 12 of the healthy individuals without myeloma included in the study, compared with only 40% of the seronegative myeloma patients, who also had lower B-cell numbers in their peripheral blood compared with the seropositive group.

Immunologists have suggested that patients with undetectable anti-S IgG antibody response after vaccination may still mount T-cell protection from severe disease, Parekh and colleagues noted.

However, "the unexpected lack of T-cell responses, coupled with an absence of anti-S antibodies following SARS-CoV-2 vaccination, particularly in multiple myeloma patients actively receiving anti-CD38 and anti-BCMA antibody-based therapies, is of concern, and it emphasizes the need for serological testing after vaccination to identify this specific subgroup of multiple myeloma patients," they wrote.

With the spread of the Delta variant, continuing safety precautions, passive antibody treatments, and booster vaccinations should be considered in order to prevent morbidity and mortality from COVID-19 in patients with suboptimal responses to vaccination, they added.

"If you don't have antibodies, you can't assume you have protection," Parekh told 口袋女优. "We've been counseling our patients to get their booster vaccinations as soon as they can."

"And now that these patients are getting boosters, the results have been encouraging," he noted. "We are seeing that about 90% of patients actually mount a phenomenal response to the booster, including about two-thirds of patients who had no response to the standard vaccines."

In the study, Parekh and colleagues profiled B-cell and T-cell responses in 44 patients with multiple myeloma who were treated at Mount Sinai (17 seronegative and 27 seropositive), as well as 12 healthy individuals, at least 2 weeks after their second vaccine dose. Most patients received the Pfizer-BioNTech vaccine, while 14 received the Moderna vaccine. Thirteen of 17 seronegative patients were either on anti-BCMA or anti-CD38 therapies.

"There seems to be a very strong biological connection between antibody responses and T-cell responses, and it seems the common underlying reason that we uncovered was that patients on some of these treatments were actually depleted of B cells, and that both their B cell and CD4 counts were low," Parekh said. "I think there is still biology to be discovered where the lack of B cells not only compromises the ability to make antibodies, but also the ability to educate T cells and form sufficient T-cell response."

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