Depletion of CD38‐positive regulatory T cells by anti‐CD38 monoclonal antibodies induces a durable response to SARS‐CoV‐2 vaccination in patients with plasma cell dyscrasia

Abstract

Summary This study reports the relationship between CD38+ regulatory T cells (Tregs) and messenger RNA coronavirus disease 2019 (mRNA‐COVID‐19) vaccination in 60 patients with plasma cell dyscrasia. Patients treated with anti‐CD38 monoclonal antibodies (mAbs) had significantly lower CD38+ Tregs than those not treated (0.9 vs. 13.2/μl). Late‐responders, whose antibody titres increased from weeks 4–12 after the second vaccination, had significantly lower CD38+ Treg counts than non‐late‐responders (2.5 vs. 10.3/μl). Antibody titres in patients with lower CD38+ Treg levels were maintained from weeks 4–12 but decreased in those with higher CD38+ Treg levels. Therefore, depletion of CD38+ Tregs by anti‐CD38 mAbs may induce a durable response to mRNA‐COVID‐19 vaccination.

Antibody status following booster vaccination against SARS‐CoV‐2 virus in patients with haematologic malignancies

“…Booster vaccination was found to increase antibody titres in patients receiving drugs previously shown to inhibit antibody production after D2, including proteasome inhibitor (PI), immunomodulatory drugs (IMiDs), anti‐CD38 monoclonal antibody, cytoreductive therapy, Janus kinase (JAK)‐1/2 inhibitor, hypomethylating agent (HMA) and tyrosine kinase inhibitor (TKI). Interestingly, four patients treated with CD38 antibodies who were seronegative at D2 became seropositive pre D3, approximately five months later, which may correspond to the late responder in patients treated with CD38 antibody therapy that we reported earlier 12 …”

“…Interestingly, four patients treated with CD38 antibodies who were seronegative at D2 became seropositive pre D3, approximately five months later, which may correspond to the late responder in patients treated with CD38 antibody therapy that we reported earlier. 12 …”

Serological response to SARS‐CoV‐2 mRNA‐containing lipid nanoparticle vaccine in patients with multiple myeloma: A negative impact of CD38+ regulatory T cells?

“…In this issue of the journal, Terao et al 10 report the impact of CD38 + Treg depletion with anti‐CD38 mAbs on serological response to two doses of anti‐SARS‐Cov‐2 mRNA vaccine in 60 patients with plasma cell dyscrasia. In all, 59 patients were given the BNT162b2 and one the mRNA‐1273 vaccine.…”

“…These findings are of interest as they provide indirect evidence that CD38 + Treg may shut down immune response to mRNA vaccines. However, there are a few limitations in the study by Terao et al 10 including the fact that FoxP3 staining was not used to define Treg (they were defined as CD4 + CD25 + CD127 dim cells, which is suboptimal) as well as the fact that neutralising Ab as well as T‐cell responses to the vaccine were not assessed. Nevertheless, the study by Terao et al 10 provides a good background to stimulate further research aimed at investigating the impact of CD38 + Treg and CD38 + Tfr on mRNA vaccine immunogenicity.…”

“…(A) Blood counts at baseline and serological response to the vaccine in patients on anti‐CD38 mAbs within 3 months before first vaccine versus in other patients in the study by Terao et al 10 T1, 4 weeks after second vaccine; T2, 12 weeks after second vaccine. (B) CD19 and CD38 + Treg counts in late responders (defined as patients whose anti‐S IgG increased from T1 to T2) versus in non‐late responders in the study by Terao et al 10 anti‐S, anti‐spike; Ig, immunoglobulin; mABs, monoclonal antibodies; Treg, regulatory T cell…”