A Canadian Perspective on the Use of Immunoglobulin Therapy to Reduce Infectious Complications in Chronic Lymphocytic Leukemia

Abstract

Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (cll), who typically have increased susceptibility because of hypogammaglobulinemia (hgg) related to their disease and its treatment. Immunoglobulin replacement therapy (igrt) has been shown to reduce the frequency of bacterial infections and associated hospitalizations in patients with hgg or a history of infection, or both. However, use of igrt in cll is contentious. Studies examining such treatment were conducted largely before the use of newer chemoimmunotherapies, which can extend lifespan, but do not correct the hgg inherent to the disease. Thus, the utility of igrt has to be re-evaluated in the current setting. Here, we discuss the evidence for the use of igrt in cll and provide a practical approach to its use in the prevention and management of infections.

Managing hypogammaglobulinaemia secondary to haematological malignancies in Australia and New Zealand: a clinician survey

“…Hypogammaglobulinaemia is a common complication of B‐cell malignancies, such as chronic lymphocytic leukaemia, myeloma and indolent non‐Hodgkin lymphoma, and is associated with an increased incidence of severe infections . The prevalence of hypogammaglobulinaemia is expected to rise due to increased use of potent B‐cell targeted therapies, such as anti‐CD20 antibodies, Bruton tyrosine kinase inhibitors and chimeric antigen receptor T‐cells, all of which can contribute to secondary hypogammaglobulinaemia as well as improve disease‐specific survival …”

“…Recommended measures to prevent infection in secondary hypogammaglobulinaemia include immunoglobulin (Ig) replacement, prophylactic antibiotics and vaccination . Of these, only Ig replacement is shown to reduce major infections in secondary hypogammaglobulinaemia, but this comes at considerable cost. In Australia, one of the highest per capita users of Ig worldwide, Ig use is rising at more than 10% per year, with acquired hypogammaglobulinaemia due to haematological malignancies comprising the largest single indication .…”

Management of patients with malignancies and secondary immunodeficiencies treated with immunoglobulins in clinical practice: Long‐term data of the SIGNS study

“…Patients with chronic lymphatic leukaemia (CLL), multiple myeloma (MM), indolent lymphoma and other malignancies have increased susceptibility to bacterial infections due to hypogammaglobulinaemia caused by their underlying disease and the corresponding treatment . In CLL, hypogammaglobinaemia occurs in about 25%‐85% of patients depending on stage and disease duration .…”

The use of octagam and gammanorm in immunodeficiency associated with hematological malignancies: a prospective study from 21 French hematology departments

“…As the defective immune response in HM patients is largely due to immunoglobulin (Ig) deficiency, Ig replacement therapy (IgRT) has been proposed as a strategy to reduce the infection risk. Both intravenous (IVIg) and subcutaneous (SCIg) routes are used for Ig administration [1,[7][8][9][10].…”