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      Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review

      systematic-review

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          Abstract

          Introduction

          Patients with hematological malignancies (HMs), like chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), have a high risk of secondary immunodeficiency (SID), SID-related infections, and mortality. Here, we report the results of a systematic literature review on the potential association of various cancer regimens with infection rates, neutropenia, lymphocytopenia, or hypogammaglobulinemia, indicative of SID.

          Methods

          A systematic literature search was performed in 03/2022 using PubMed to search for clinical trials that mentioned in the title and/or abstract selected cancer (CLL, MM, or NHL) treatments covering 12 classes of drugs, including B-lineage monoclonal antibodies, CAR T therapies, proteasome inhibitors, kinase inhibitors, immunomodulators, antimetabolites, anti-tumor antibiotics, alkylating agents, Bcl-2 antagonists, histone deacetylase inhibitors, vinca alkaloids, and selective inhibitors of nuclear export. To be included, a publication had to report at least one of the following: percentages of patients with any grade and/or grade ≥3 infections, any grade and/or grade ≥3 neutropenia, or hypogammaglobulinemia. From the relevant publications, the percentages of patients with lymphocytopenia and specific types of infection (fungal, viral, bacterial, respiratory [upper or lower respiratory tract], bronchitis, pneumonia, urinary tract infection, skin, gastrointestinal, and sepsis) were collected.

          Results

          Of 89 relevant studies, 17, 38, and 34 included patients with CLL, MM, and NHL, respectively. In CLL, MM, and NHL, any grade infections were seen in 51.3%, 35.9% and 31.1% of patients, and any grade neutropenia in 36.3%, 36.4%, and 35.4% of patients, respectively. The highest proportion of patients with grade ≥3 infections across classes of drugs were: 41.0% in patients with MM treated with a B-lineage monoclonal antibody combination; and 29.9% and 38.0% of patients with CLL and NHL treated with a kinase inhibitor combination, respectively. In the limited studies, the mean percentage of patients with lymphocytopenia was 1.9%, 11.9%, and 38.6% in CLL, MM, and NHL, respectively. Two studies reported the proportion of patients with hypogammaglobulinemia: 0–15.3% in CLL and 5.9% in NHL (no studies reported hypogammaglobulinemia in MM).

          Conclusion

          This review highlights cancer treatments contributing to infections and neutropenia, potentially related to SID, and shows underreporting of hypogammaglobulinemia and lymphocytopenia before and during HM therapies.

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          Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents.

          The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy. Although largely neglected in the clinical practice, accumulating evidence indicates that the efficacy of conventional and targeted anticancer agents does not only involve direct cytostatic/cytotoxic effects, but also relies on the (re)activation of tumor-targeting immune responses. Chemotherapy can promote such responses by increasing the immunogenicity of malignant cells, or by inhibiting immunosuppressive circuitries that are established by developing neoplasms. These immunological "side" effects of chemotherapy are desirable, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy.
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            An introduction to immunology and immunopathology

            Beyond structural and chemical barriers to pathogens, the immune system has two fundamental lines of defense: innate immunity and adaptive immunity. Innate immunity is the first immunological mechanism for fighting against an intruding pathogen. It is a rapid immune response, initiated within minutes or hours after aggression, that has no immunologic memory. Adaptive immunity, on the other hand, is antigen-dependent and antigen-specific; it has the capacity for memory, which enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen. There is a great deal of synergy between the adaptive immune system and its innate counterpart, and defects in either system can provoke illness or disease, such as inappropriate inflammation, autoimmune diseases, immunodeficiency disorders and hypersensitivity reactions. This article provides a practical overview of innate and adaptive immunity, and describes how these host defense mechanisms are involved in both heath and illness.
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              Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial

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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                07 February 2023
                2023
                : 13
                : 1098326
                Affiliations
                [1] 1 Immunodeficiency Centre for Wales, University Hospital of Wales , Cardiff, United Kingdom
                [2] 2 Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center , New York, NY, United States
                [3] 3 Faculty of Medicine and Health Sciences, Ghent University Hospital , Ghent, Belgium
                [4] 4 Department of Medicine, Hematology-Oncology, Case Western Reserve University , Cleveland, OH, United States
                [5] 5 Rochester Regional Health , Rochester, NY, United States
                [6] 6 Department of Medicine, Allergy/Immunology and Rheumatology, University of Rochester , Rochester, NY, United States
                [7] 7 Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro Medical School , Bari, Italy
                [8] 8 Department of Medicine, McGill University Health Centre , Montreal, QC, Canada
                Author notes

                Edited by: Robert Ohgami, The University of Utah, United States

                Reviewed by: Joshua Richter, Icahn School of Medicine at Mount Sinai, United States; Rahul Banerjee, University of Washington, United States

                *Correspondence: Stephen Jolles, JollesSR@ 123456cardiff.ac.uk

                †ORCID: Stephen Jolles, orcid.org/0000-0002-7394-6804

                This article was submitted to Hematologic Malignancies, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2023.1098326
                9941665
                36824125
                afd7125d-19f3-48c5-807f-3cc712b7a01f
                Copyright © 2023 Jolles, Giralt, Kerre, Lazarus, Mustafa, Ria and Vinh

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 November 2022
                : 04 January 2023
                Page count
                Figures: 1, Tables: 6, Equations: 0, References: 149, Pages: 17, Words: 9519
                Funding
                Funded by: CSL Behring , doi 10.13039/100008322;
                Categories
                Oncology
                Systematic Review

                Oncology & Radiotherapy
                secondary immunodeficiency,hematological malignances,neutropenia,hypogammaglobulinemia,secondary antibody deficiency,b-lineage monoclonal antibodies,bruton kinase inhibitors

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