COVID-19 in multiple-myeloma patients: cellular and humoral immunity against SARS-CoV-2 in a short- and long-term view

Abstract

Multiple myeloma patients are often treated with immunomodulatory drugs, proteasome inhibitors, or monoclonal antibodies until disease progression. Continuous therapy in combination with the underlying disease frequently results in severe humoral and cellular immunodeficiency, which often manifests in recurrent infections. Here, we report on the clinical management and immunological data of three multiple-myeloma patients diagnosed with COVID-19. Despite severe hypogammaglobulinemia, deteriorated T cell counts, and neutropenia, the patients were able to combat COVID-19 by balanced response of innate immunity, strong CD8+ and CD4+ T cell activation and differentiation, development of specific T-cell memory subsets, and development of anti-SARS-CoV-2 type IgM and IgG antibodies with virus-neutralizing capacities. Even 12 months after re-introduction of lenalidomide maintenance therapy, antibody levels and virus-neutralizing antibody titers remained detectable, indicating persisting immunity against SARS-CoV-2. We conclude that in MM patients who tested positive for SARS-CoV-2 and were receiving active MM treatment, immune response assessment could be a useful tool to help guide decision-making regarding the continuation of anti-tumor therapy and supportive therapy. Key messages Immunosuppression due to multiple myeloma might not be the crucial factor that is affecting the course of COVID-19. In this case, despite pre-existing severe deficits in CD4+ T-cell counts and IgA und IgM deficiency, we noticed a robust humoral and cellular immune response against SARS-CoV-2. Evaluation of immune response and antibody titers in MM patients that were tested positive for SARS-CoV-2 and are on active MM treatment should be performed on a larger scale; the findings might affect further treatment recommendations for COVID-19, MM treatment re-introduction, and isolation measures.

Impact of Hypogammaglobulinemia on the Course of COVID-19 in a Non-Intensive Care Setting: A Single-Center Retrospective Cohort Study

“…Indeed their co-occurrence might reasonably enhance COVID-19 severity. Bronchiectasis had already been included in proposed models of disease severity prediction (28), and also oncologic and onco-hematologic diseases that might broaden the risk for infectious (including opportunistic) complications, as for the immunoparesis in MM (18)(19)(20)29). Compared to the above mentioned, however, the advantage of hypogammaglobulinemia is the possibility of promptly restoring and keeping normal IgG serum levels by IgRT (30).…”

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

“…Next, we focused on variant-specific T cell responses 1–3 months after the booster vaccination. 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 ).…”

Luteolin Potentially Treating Prostate Cancer and COVID-19 Analyzed by the Bioinformatics Approach: Clinical Findings and Drug Targets

“…Statistical analysis data indicate that non-infectious conditions, such as diabetes and cancers, have numerous cases worldwide (30). Among cancer cases, the tumor microenvironment may be altered via depositing metabolites as a result of reduced immunity (31), possibly causing increased risk of infections including SARS-CoV-2 (32). It is presently reported that the COVID-19 pandemic and uncertain SARS-CoV-2 variants are still persisting and evolving diffusely.…”