SARS-CoV-2 mRNA vaccination-induced immune responses vary among patients with hematologic malignancies, with some having persistent lack of serological response after 3 vaccinations, according to a report published in Blood Cancer Discovery.

Researchers evaluated the 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 National Registry and a next generation sequencing-based molecular assay 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 lymphoma (30.5%). Patients who were ≥65 years of age comprised 66.9% of the cohort. Patients received either the mRNA-1273 (46.7%) or BNT162b2 (53.3%) mRNA vaccine.

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After the second vaccine dose, the researchers found that 58% of sero-positive and 45% of sero-negative patients display anti-spike T-cells. They also observed that the percentage of patients who were T-cell positive was higher among patients who received mRNA-1273 vaccines compared with those who received BNT162b2 vaccines (52% vs 40%; P =.001).

After the third vaccine dose, the team found that 40% of patients seroconverted but that only 22% produced antibody levels associated with the production of neutralizing antibodies. They also found that the 97% of patients who were sero-positive before the third vaccine dose had markedly elevated 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 are depressed by B-cell suppressive or depleting therapies, including BTK inhibitors, anti-CD20 antibodies, or both. They demonstrated that patients who had no treatment showed a marked increase in anti-spike antibody levels (median, 112 AU/mL to 2500 AU/mL) before and after the third SARS-CoV-2 mRNA vaccine dose, whereas those on treatment displayed a smaller increase (median, 0.4 AU/mL to 10 AU/mL).

“Vaccinated patients with B cell malignancies with a poor response to SARS-CoV-2 vaccines may remain vulnerable to COVID-19 infections,” explained the authors. “Our data supports the utility of a third vaccination for patients with B cell malignancies.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Greenberger LM, Saltzman LA, Gruenbaum LM, et al. Anti-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