Research Underscores the Need for Serological Testing After COVID-19 Vaccination in Multiple Myeloma

Samir Parekh, MD

A proportion of patients with multiple myeloma receiving CD38-directed and BCMA-directed therapies had a lack of T-cell responses and an absence of anti–SARS-CoV-2 Spike (anti-S) antibodies following SARS-CoV-2 vaccination, underscoring the need for serological testing after vaccination to identify these patients, according to a research letter that was published in Cancer Cell.¹

“With the current rapid spread of a more transmissible viral variant, the Delta variant, booster vaccination, continuing safety precautions, and passive antibody treatments should be considered to prevent severe disease and death in multiple myeloma patients with poor vaccine responses,” said senior study author Samir Parekh, MD, director of Translational Research in Multiple Myeloma at The Tisch Cancer Institute and a professor of medicine (hematology and medical oncology) and oncological sciences at the Icahn School of Medicine at Mount Sinai in a news release.²

Although SARS-CoV-2 vaccines have demonstrated efficacy in preventing severe disease and mortality among healthy individuals, immunocompromised people with hematologic malignancies, such as multiple myeloma, have an increased risk of developing severe COVID-19–related infections.¹

Recently published data showed that patients with multiple myeloma have variable anti-S IgG antibody responses following 2 vaccine doses. Moreover, 15% of patients had a complete absence of antibody responses.

“We wanted to determine whether patients [with multiple myeloma] without detectable anti-S IgG antibodies to SARS-CoV-2 immunization, seronegative, had detectable SARS-CoV-2 B- and T-cell responses after SARS-CoV-2 vaccination, which would possibly provide some protection against severe disease even in the absence of anti-S antibodies,” lead study author Adolfo Aleman, a PhD student in the Clinical Research Program at the Icahn School of Medicine at Mount Sinai, and coauthors wrote.¹

Moreover, data such as these could provide insight into guidelines for masking, social distancing, and passive antibody or booster vaccination strategies among patients with multiple myeloma who are receiving anti-cancer therapies.

In the study, a high-resolution flow cytometry assay utilizing multiple cytokines and activation markers was utilized to assess quantitative and qualitative differences in T-cell responses among 44 patients with multiple myeloma and 12 healthy individuals. Within the multiple myeloma population, 17 patients were seronegative and 27 were seropositive.

Participants were profiled at least 2 weeks following their second mRNA SARS-CoV-2 vaccine dose. Individuals had received the BNT162b2 Pfizer-BioNTech vaccine (n = 42) or the mRNA-1273 Moderna vaccine (n = 14).

Most seronegative patients (n = 13; 76%) were receiving BCMA- or CD38-directed therapy for their multiple myeloma.

The results showed that spike-protein-reactive B cells were detected in most seropositive patients (n = 24; 96%) and all healthy individuals, but in 40% (n = 6) of seronegative patients. Seronegative patients also had lower B-cell numbers in their peripheral blood vs seropositive patients (P < .0015).

Direct correlations were observed between the presence of spike-protein-reactive B cells and anti-S IgG antibody concentration (Spearman R = 0.44; P = .002) and between absolute B-cell count and anti-S IgG concentration (Spearman R = 0.51; P = .00047). Additionally, seronegative patients had significantly reduced total CD4+ T-cell counts vs seropositive patients (P = .0065). No differences between total white blood cell, lymphocyte, neutrophil, monocyte, or total CD8+ T cell-counts were observed.

Seropositive patients with multiple myeloma were found to have similar levels of IFN-γ, TFN-α, IL-2, or GM-CSF–expressing CD4+ T cells compared with age-matched healthy individuals; however, seronegative patients had significantly reduced CD4+ T-cell responses (P < .005). Moreover, 35% (n = 6) of seronegative patients had a CD4+ T-cell response.

CD8+ T-cell responses did not vary significantly between cohorts: 50% of healthy individuals (n = 6) had a CD8+ T-cell response vs 50% of seropositive patients (n = 12) and 28% of seronegative patients (n = 4).

Fewer patients with multiple myeloma receiving anti-BCMA bispecific (33%; n = 2) or anti-CD38 therapies (68%; n = 13) had SARS-CoV-2–specific CD4+ T-cell responses vs patients on other anti-myeloma therapies (90%; n = 9) or BCMA-directed CAR T-cell therapy (89%; n = 9).

Additionally, cytokine-expression monofunctional and polyfunctional T cells were distributed similarly between seropositive and healthy individuals; however, seronegative patients demonstrated a dominant IL-2 monofunctional T-cell response.

References

1. Aleman A, Upadhyaya B, Tuballes K, et al. Variable cellular responses to SARS-CoV-2 in fully vaccinated patients with multiple myeloma. Cancer Cell. Published online October 19, 2021. Accessed October 22, 2021. doi:10.1016/j.ccell.2021.09.015
2. Cancer patients with poor antibody response to COVID-19 vaccines also lack secondary immune response, study shows. News release. Mount Sinai. October 18, 2021. Accessed October 22, 2021. https://bit.ly/3nhhadf