Researchers have demonstrated the clinical importance of COVID-19 vaccination after anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with B-cell lymphoma. The pair of studies, published in Blood, describe the intact T-cell mediated mechanisms following SARS-CoV-2 messenger RNA (mRNA) vaccination in these patients.
Despite the effectiveness of mRNA vaccines against COVID-19, patients with B-cell lymphomas develop insufficient antibody responses to the vaccines due to treatment-induced immunosuppression.
However, in addition to the antibody response, the T-cell response is another critical component of immune protection against SARS-CoV-2. Vaccine-induced T-cell responses therefore have the potential to “salvage” protective immunity in patients with B-cell lymphoma.
The first paper, by Djordje Atanackovic, MD, and colleagues at the University of Maryland School of Medicine in Baltimore, described a prospective, single-center clinical study evaluating immune responses to two different COVID-19 mRNA vaccines.
The study enrolled patients with B-cell lymphomas treated with anti-CD19 CAR T cells (n=18) and healthy controls (n=10). Of the 18 lymphoma patients, 10 received the mRNA-1273 (Moderna) vaccine, and eight received the BNT162b2 (Pfizer/BioNTech) vaccine. Dr. Atanackovic and colleagues noted that the study was limited by its small size.
The results showed that although the patients were incapable of developing vaccine-induced antibody responses against SARS-CoV-2 because of potent B-cell depletion, they were nevertheless capable of developing anti-SARS-CoV-2 T cells that even recognize the Omicron variant, which is known for its ability to evade antibody responses.
“After [two] initial doses of mRNA vaccine, the number of virus-specific T cells was equal to and sometimes even surpassed that of healthy, vaccinated controls as well as patients with active COVID-19 infection,” the authors wrote.
The second paper, by Dr. Bernice Ling Zhi Oh and colleagues at the National University Hospital in Singapore, longitudinally studied anti-CD19 CAR T-cell–treated patients, mostly adolescents and young adults, before and after the first and second dose of vaccination with the BNT162b2 mRNA vaccine.
The results showed a stronger induction of spike-specific T cells after vaccination in patients with anti-CD19 CAR T-cells compared with healthy individuals, although the augmented response was only evident after the second vaccine dose. The enhanced T-cell response was effective against both the Delta and Omicron variants of SARS-CoV-2.
Dr. Oh and colleagues wrote that although the study was limited by its small size, the results still support vaccination despite B-cell depletion in these patients.
“Our results support the clinical utility and importance of COVID-19 vaccination in patients after anti-CD19 CAR T-cell therapy despite B-cell aplasia,” they wrote.
Atanackovic D, Luetkens T, Omili D, et al. Vaccine-induced T-cell responses against SARS-CoV-2 and its omicron variant in patients with B cell-depleted lymphoma after CART therapy. Blood. 2022;140(2):152-156.
Oh BLZ, Tan N, de Alwis R, et al. Enhanced BNT162b2 vaccine-induced cellular immunity in anti-CD19 CAR T cell-treated patients. Blood. 2022;140(2):156-160.
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