Immune response to SARS-CoV-2 mRNA vaccination and booster dose in patients with multiple myeloma and monoclonal gammopathies: impact of Omicron variant on the humoral response

Abstract

The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of the spike variants, including Omicron, are still unclear in patients with multiple myeloma (MM) and those with pre-malignant monoclonal gammopathies. In this study, involving 40 patients, we found that MM patients with relapsed-refractory disease (MMR) had reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 vaccination. The five analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and smoldering MM. Moreover, lower spike-specific IL-2-producing CD4 + T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing CD8 + T cells were found in MM patients as compared to patients with monoclonal gammopathy of undetermined significance. We found that a heterologous booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. However, in MMR patients, Omicron retained a negative impact on neutralizing ability, suggesting further approaches to potentiating the effectiveness of SARS-CoV-2 vaccination in these patients.

Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis

“…Booster vaccination demonstrates significantly increased neutralizing titers, which is predicted to provide protection against severe SARS-CoV-2 infection with the current variants of concern, including Omicron [195][196][197]. Therefore, booster vaccination should be offered to hematologic malignancy patients, especially for patients who are seronegative or attain low neutralization levels [82,167].…”

“…Approximately 20% of hematologic malignancy patients failed to attain humoral and cellular immunity. Booster vaccination demonstrated enhancement of cellular immune responses in hematologic malignancy patients [144,160,167]. Thus, booster vaccination should be recommended for hematologic malignancy patients who are at risk for immunological failure after primary vaccination series.…”

SARS-CoV-2-Specific T Cell Responses in Immunocompromised Individuals with Cancer, HIV or Solid Organ Transplants

“…These groups are known to develop a weaker humoral immunity and similar T cell responses, compared to patients with solid cancers. Importantly, booster vaccination with a mRNA vaccine results in significant increases in humoral and cellular immune responses, including VOC [ 86 , 87 ]. However, compared to healthy individuals, the SARS-CoV-2-specific adaptive immunity may still be impaired, resulting in a higher susceptibility towards breakthrough infections.…”

Identifying the Effect of COVID-19 Infection in Multiple Myeloma and Diffuse Large B-Cell Lymphoma Patients Using Bioinformatics and System Biology

“…MM and DLBCL are also reported as high-risk factors for COVID-19 [5][6][7][8][9]. Moreover, recent studies have highlighted that the immune response to COVID-19 mRNA vaccination in MM patients, evaluated based on the neutralizing capability of vaccine-induced antibodies, is significantly compromised in the case of COVID-19 variants [10]. Accordingly, the risk of breakthrough infection with COVID-19 variants was also significantly higher in patients with MM [11].…”