Background: COVID-19 has been extensively characterized in immunocompetent hosts and to a lesser extent in immunocompromised populations. Among the latter, patients treated for B-cell malignancies have immunosuppression generated by B-cell lymphodepletion/aplasia resulting in an increased susceptibility to respiratory virus infections and poor response to vaccination. The consequence is that these patients are likely to develop severe or critical COVID-19.
Objectives: To examine the overall impact of COVID-19 in patients treated for a B-cell malignancy or receiving chimeric antigen receptor T (CAR-T) immunotherapy administered in case of relapsed or refractory disease.
Sources: We searched in the MEDLINE database to identify relevant studies, trials, reviews, or meta-analyses focusing on SARS-CoV-2 vaccination or COVID-19 management in patients treated for a B-cell malignancy or recipients of CAR-T cell therapy up to 8 July 2022.
Content: The epidemiology and outcomes of COVID-19 in patients with B-cell malignancy and CAR-T cell recipients are summarized. Vaccine efficacy in these subgroups is compiled. Considering the successive surges of variants of concern, we propose a critical appraisal of treatment strategies by discussing the use of neutralizing monoclonal antibodies, convalescent plasma therapy, direct-acting antiviral drugs, corticosteroids, and immunomodulators.
Implications: For patients with B-cell malignancy, preventive vaccination against SARS-CoV-2 remains essential and the management of COVID-19 includes control of viral replication because of protracted SARS-CoV-2 shedding. Passive immunotherapy (monoclonal neutralizing antibody therapy and convalescent plasma therapy) and direct-active antivirals, such as remdesivir and nirmatrelvir/ritonavir are the best currently available treatments. Real-world data and subgroup analyses in larger trials are warranted to assess COVID-19 therapeutics in B-cell depleted populations.
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http://dx.doi.org/10.1016/j.cmi.2022.10.030 | DOI Listing |
Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.
View Article and Find Full Text PDFJ Cancer Res Ther
December 2024
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Background: Patients with transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have limited treatment options and poor outcomes.
Methods: This phase III study (NCT04236141) evaluated the efficacy and safety of polatuzumab vedotin plus bendamustine and rituximab (Pola+BR) versus BR in Chinese patients with transplant-ineligible R/R DLBCL to support regulatory submission in China. Patients were randomized 2:1 to receive Pola+BR or placebo+BR.
Cells
January 2025
Hematology, St. Eugenio Hospital, ASL Roma2, 00144 Rome, Italy.
Despite the advances of CAR-T cells in certain hematological malignancies, mostly from B-cell derivations such as non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, a significant portion of other hematological and non-hematological pathologies can benefit from this innovative treatment, as the results of clinical studies are demonstrating. The clinical application of CAR-T in the setting of acute T-lymphoid leukemia, acute myeloid leukemia, solid tumors, autoimmune diseases and infections has encountered limitations that are different from those of hematological B-cell diseases. To overcome these restrictions, strategies based on different molecular engineering platforms have been devised and will be illustrated below.
View Article and Find Full Text PDFCells
December 2024
Department of Otorhinolaryngology, Ulm University Medical Center, 89075 Ulm, Germany.
Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells from the spleen, lymph nodes and tumors were analyzed.
View Article and Find Full Text PDFCancer Med
January 2025
Faculty of Medical Sciences, Neuroscience Research Center, Lebanese University, Hadath, Lebanon.
Background: Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median survival of less than 15 months. Advancements in the field of epigenetics have expanded our understanding of cancer biology and helped explain the molecular heterogeneity of these tumors. B-cell-specific Moloney murine leukemia virus insertion site-1 (Bmi-1) is a member of the highly conserved polycomb group (PcG) protein family that acts as a transcriptional repressor of multiple genes, including those that determine cell proliferation and differentiation.
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