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

Oncoimmunology. 2022 Sep 6;11(1):2120275. doi: 10.1080/2162402X.2022.2120275. eCollection 2022.

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.

Keywords: Multiple myeloma; Omicron; SARS-CoV-2; monoclonal gammopathies; neutralizing antibodies; spike variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • CD8-Positive T-Lymphocytes
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Immunity
  • Multiple Myeloma*
  • RNA, Messenger
  • SARS-CoV-2
  • Vaccination
  • Viral Vaccines* / genetics

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • RNA, Messenger
  • Viral Vaccines

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

This study was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC) under IG IG2017 ID. 20299 project; International Myeloma Society (IMS) under “Paula and Rodeger Riney Foundation Translational Research Grant” (PI Nicola Giuliani); and Associazione Italiana contro Leucemie, Linfomi e Mielomi ONLUS, ParmAIL.