In an article published in Blood Cancer Discovery, the authors summarized 2 recent studies demonstrating that completion of mRNA-based vaccination does not yield detectable SARS-CoV-2 Omicron-neutralizing antibodies in most patients with multiple myeloma (MM), non-Hodgkin (NHL), or chronic lymphocytic leukemia (CLL).1

The 2 independent studies investigated immune responses elicited by 3 vaccinations with mRNA-based vaccines (Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) against the SARS-CoV-2 variants of concern (VOC) in patients with MM and those with NHL/CLL.

Both studies examined neutralizing antibody (nAb) titers using live-virus neutralization.1-3 They demonstrated that 3 doses of SARS-CoV-2 mRNA vaccines failed to generate detectable Omicron BA.1 or BA.5-specific neutralizing antibodies in 60% of patients with MM and 57% of patients with NHL/CLL.2,3

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In the MM cohort, patients had an increase in Omicron spike-reactive CD4+ Th1 cells but no increase relative to background levels in Omicron spike protein receptor-binding domain-specific CD8+ T cells. Patients who developed breakthrough infections following vaccination had low levels of live-virus nAb and follicular T helper cells (CXCR5+CD4+) compared with patients with no COVID-19.2

“Future strategies applicable to [patients with hematologic malignancies] might also include the development of broadly neutralizing antibodies for passive immunization or that of vaccines specifically designed to induce Omicron-specific CD8+ T-cell responses with [type 1cytotoxic] polarity,” the authors explained in their report.

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


  1. Zitvogel L, Derosa L, Kroemer G. Defective immunity against SARS-CoV-2 Omicron variants despite full vaccination in hematologic malignancies. Blood Cancer Discov. 2023;4(3):172-175. doi:10.1158/2643-3230.BCD-22-0213
  2. Azeem MI, Nooka AK, Shanmugasundaram U, et al. Impaired SARS-CoV-2 variant neutralization and CD8+ T-cell responses following 3 doses of mRNA vaccines in myeloma: correlation with breakthrough infections. Blood Cancer Discov. 2023;4(2):106-117. doi:10.1158/2643-3230.BCD-22-0173
  3. Chang A, Akhtar A, Lai L, et al. Antibody binding and neutralization of live SARS-CoV-2 variants including BA.4/5 following booster vaccination of patients with B-cell malignancies. Cancer Res Commun. 2022;2(12):1684-1692. doi:10.1158/2767-9764.crc-22-0471