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Immune response to SARS-CoV-2 mRNA vaccines varies among patients with hematologic malignancies

According to a report published in the journal Blood Cancer Discovery, immune responses induced by SARS-CoV-2 mRNA vaccination are variable in patients with hematological malignancies, with some having a persistent lack of serological response after 3 vaccinations.

Researchers evaluated anti-spike T-cell and antibody responses to SARS-CoV-2 mRNA vaccines (BNT162b2 and mRNA-1273) in patients with B-cell malignancies in a real-world setting. They used data from the Leukemia and Lymphoma Society’s National Registry and next-generation sequencing-based molecular analysis to assess SARS-CoV-2-specific T cell responses.

A total of 505 patients were included in the analysis, most of whom had chronic lymphocytic leukemia (56%) and non-Hodgkin’s lymphoma (30.5%). Patients aged ≥65 years comprised 66.9% of the cohort. Patients received either mRNA-1273 (46.7%) or BNT162b2 (53.3%) mRNA vaccine.

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After the second dose of the vaccine, the researchers found that 58% of seropositive and 45% of seronegative patients showed anti-spike T cells. They also observed that the percentage of T-cell positive patients was higher among patients receiving the mRNA-1273 vaccine compared with those receiving the BNT162b2 vaccine (52% vs. 40%; P = 0.001).

After the third vaccine dose, the team found that 40% of patients seroconverted, but only 22% developed antibody levels associated with neutralizing antibody production. They also found that 97% of patients who were seropositive before the third dose of vaccine had a sharp increase in anti-spike antibody levels after the third dose (median, 231 AU/ml vs 2500 AU/ml).

The researchers also found that anti-spike antibody levels were reduced by treatments that suppress or deplete B cells, including BTK inhibitors, anti-CD20 antibodies, or both. They showed that treatment-naïve patients had an increase in anti-spike antibody levels (median, 112 AU/ml to 2500 AU/ml) before and after the third dose of SARS-CoV-2 mRNA vaccine, whereas treated patients showed a smaller increase (median, 0.4 AU/mL to 10 AU/mL).

“Vaccine patients with B-cell malignancies who respond poorly to SARS-CoV-2 vaccines may remain vulnerable to COVID-19 infections,” the authors explained. “Our data support the benefit of a third vaccination in patients with B-cell malignancies.”

Disclosure: Some study authors reported affiliation with biotechnology, pharmaceutical, or device companies. See the original reference for a full list of author disclosures.


Greenberger LM, Saltzman LA, Gruenbaum LM, et al. Spike T cell and antibody responses to SARS-CoV-2 mRNA vaccines in patients with hematologic malignancies. Published online September 8, 2022. Blood Cancer Discov. doi:10.1158/2643-3230.BCD-22-0077