Subgroup of Patients With MM Show Lower T-Cell Count Against COVID-19

Researchers assessed patients with multiple myeloma (MM) without detectable Spike (anti-S) IgG antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization to develop stronger protection in the absence of crucial T-cell responses.

“SARS-CoV-2 vaccines have been proven to be highly effectively at preventing severe disease and mortality; however, immunocompromised individuals with hematologic malignancies are at increased risk of severe COVID-19 manifestations. The production of SARS-CoV-2 T-cell immunity is much lower in this patient population,” explained Adolfo Aleman, MD, Icahn School of Medicine at Mount Sinai, New York, and co-investigators.

T-cell responses were studied for quantitative and qualitative differences with a high-resolution flow cytometry assay that incorporated multiple cytokines and activation markers.

“Data are urgently required to guide masking, social distancing, and passive antibody and booster vaccination strategies for potentially vulnerable patients with MM treated with anti-cancer agents as the COVID-19 pandemic continues,” continued Dr Aleman and co-authors.

B- and T-cell responses were evaluated in 44 patients with MM (17 seronegative and 27 seropositive) and 12 healthy patients at least 2 weeks after their second mRNA SARS-CoV-2 vaccine dose (Pfizer-BioTech, n=42; Moderna, n=14). Notably, the majority (76%) of seronegative patients were either on anti-BCMA or anti-CD38 therapies.

“Although spike-protein-reactive B-cells were detected in all but one seropositive MM patients (96%) and all healthy individuals, only 40 percent of the seronegative patients with MM harbored spike-protein-reactive B-cells. Seronegative patients also had lower B-cell numbers in their peripheral blood compared to the seropositive MM group,” elaborated Dr Aleman and co-researchers.

The study identified a direct correlation between the presence of spike-reactive B-cells and anti-S IgG antibody concentration (spearman r=0.44, P=0.002) and a direct correlation between absolute B-cell count and anti-S IgG antibody concentration (spearman r=0.51, P=0.00047).

Distributions of cytokine-expressing monofunctional and polyfunctional CD4-positive T-cells were very similar between seropositive and healthy controls, and IL-2 and IFN-y-cytokine-alone-expression CD4-positive T-cells were the dominant fraction within the total cytokine response.

Further, a high degree of variability in SARS-CoV-2-specific B and T-cell responses were observed in patients with MM.

“The unexpected lack of T-cell responses, coupled with an absence of anti-S antibodies following SARS-CoV-2 vaccination, particularly in patients actively receiving anti-CD38 and anti-BCMA antibody-based therapies is of concern. It emphasizes the need for serological testing after vaccination to identify this specific subgroup of MM patients,” concluded Dr Aleman, et al.—Alexa Stoia