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Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia

ABSTRACT: Secondary immunodeficiency is reported in most patients with hematological malignancies such as chronic lymphocytic leukemia and multiple myeloma. The aim of our review was to evaluate the existing literature data on patients with hematological malignancies, with regard to the effect of immunodeficiency on the outcome, the clinical and therapeutic approach, and on the onset of noninfectious complications, including thrombosis, pleural effusion, and orofacial complications. Immunodeficiency in these patients has an intense impact on their risk of infection, in turn increasing morbidity and mortality even years after treatment completion. However, these patients with increased risk of severe infectious diseases could be treated with adequate vaccination coverage, but the vaccines’ administration can be associated with a decreased immune response and an augmented risk of adverse reactions. Probably, immunogenicity of the inactivated is analogous to that of healthy subjects at the moment of vaccination, but it undertakes a gradual weakening over time. However, the dispensation of live attenuated viral vaccines is controversial because of the risk of the activation of vaccine viruses. A particular immunization schedule should be employed according to the clinical and immunological condition of each of these patients to guarantee a constant immune response without any risks to the patients’ health.

SUBMITTER: Allegra A

PROVIDER: S-EPMC8573331 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPatients 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.MethodsA 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.ResultsOf 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).ConclusionThis 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.

Project description:AbstractUnlike Western countries, there are still few clinical immunology specialists in China, and the optimal care for secondary immunodeficiency caused by hematological malignancies is unknown. Therefore, we initiated this clinician survey study to describe the current situation of the care for malignancy patients with hypogammaglobulinemia in China.We adapted a previously published online questionnaire of current clinical practices regarding the management of secondary immunodeficiency caused by hematological malignancies and then distributed the questionnaire to 52 hematologists in China via WeChat mobile software; the survey collected demographic details, starting dosage, target immunoglobulin (Ig) level, monitoring, criteria for stopping Ig replacement, vaccination use, and oral antibiotic prophylaxis for hypogammaglobulinemia patients.Forty-eight hematologists responded. 28(58.33%) respondents had more than 10 years of experience. Nevertheless, 40(83.33%) respondents reported that they did not use any specific criteria for prophylactic Ig replacement in hypogammaglobulinemia patients. However, 27(56.25%) respondents reported that they had used intravenous immunoglobulin (IVIG); however, the starting dose, frequency, and target Ig level were significantly varied. Additionally, the criteria for stopping Ig replacement were significantly varied. Only one respondent (2.08%) used subcutaneous immunoglobulin (SCIG). Moreover, 35(72.92%) respondents reported no vaccination prior to Ig replacement, and 47(97.92%) respondents reported that they had not used antibiotic prophylaxis in secondary hypogammaglobulinemia patients.Official guideline for the care for secondary immunodeficiency (SID) of the hematological malignancies patients should be issued in China, and significant attention of the hematologists should be paid to the use of prophylactic antibiotics and Ig replacement for the care of patients with hypogammaglobulinemia caused by hematological malignancies, as these agents could significantly reduce the infection rate in China.

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Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia

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