Severe impairment of T-cell responses to BNT162b2 immunization in patients with multiple myeloma

Abstract

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

Enhanced but variant-dependent serological and cellular immune responses to third-dose BNT162b2 vaccination in patients with multiple myeloma

“…We and others previously reported variable vaccination responses in patients with MM after two doses of BNT162b2 ( Aleman et al., 2021 ; Ehmsen et al., 2021 ; Enβle et al., 2022 ; van Oekelen et al., 2021 ). In our interim analysis, among patients with MM, we identified 53.2% serological responders (neutralization titer [NT] ≥ 1:20) to the wildtype (WT) and 43.6% serological responders to the B.1.1.7 (Alpha) variant, whereas 34.2% of the patients were classified as T cell responders ( Enβle et al., 2022 ; Khoury et al., 2021 ). Factors that were predictive of poor response were older age, active treatment excluding maintenance, low CD19 + B cell counts, and the presence of immunoparesis.…”

“…Previously, we hypothesized that T cell responses might be necessary in patients with B cell deficiency to achieve a maximal vaccination response ( von Metzler et al., 2021 ). However, after the second dose of vaccine, we reported abrogated T cell responses in patients with MM compared with healthy individuals ( Enβle et al., 2022 ). After the third vaccination, we expanded our analysis and used flow cytometry to examine WT-, Delta-, and Omicron-specific T cell subsets and activation.…”

Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19

“…While the administration of mRNA vaccines has effectively reduced COVID-19-related severe disease, hospital admissions, and mortality in healthy adults [44][45][46], vaccine efficacy has not been as high in other target populations. In fact, different studies have reported lower rates of immune responses after vaccination in patients with hematologic pathologies (chronic lymphatic leukemia, multiple myeloma, lymphoma, and myeloproliferative malignancies) [47][48][49][50], as well as in solid organ transplant recipients [51][52][53][54]. In this scenario, it may be interesting to have new alternative therapies available that focus on increasing the individual immune response against the SARS-CoV-2 infection.…”

Cellular Immune Response after Vaccination in Patients with Cancer—Review on Past and Present Experiences

“…Agammaglobulinemia patients were shown to recover from COVID-19 without adequate serological responses, suggesting a T cell response to be sufficient for recovery from disease and even for mounting protection from infection [99,100]. An undetectable B cell and reduced T cell response in many hematological patients (ranging from 34.2 to 79.0%) compared to healthy controls or solid tumor patients has so far been reported [31,61,62,101,102]. Age (>65 years), active disease, immunosuppressive treatment for GvHD, and lymphopenia were associated with impaired cellular response.…”