Rational Use of Immunoglobulin in Adult Patients with Secondary Hypogammaglobulinemia in the Setting of Hematologic Malignancy: A Canadian Perspective

Hypogammaglobulinemia is identified by the detection of low serum immunoglobulin (Ig) levels. Secondary hypogammaglobulinemia (SHG) is an acquired state in which circulating Ig levels are reduced due to suppressed antibody production or increased antibody loss. Specifically, SHG most commonly refers to low circulating total IgG levels. In contrast, primary hypogammaglobulinemia (PHG) is due to an underlying inborn error of immunity contributing to low or defective Ig production and frequent and/or severe infections. In patients with hematologic malignancies, it is important to evaluate baseline Ig (IgG, IgM, IgA) levels at the time of diagnosis. However, it may be challenging to distinguish whether low Ig levels are attributable to PHG or SHG, if antibody defects are identified in the context of hematologic malignancies (including chronic lymphocytic leukemia [CLL], lymphoma, and multiple myeloma), even before initiation of immunosuppressive treatment. PHG should be considered, especially in younger patients presenting with a hematologic malignancy who have a history of recurrent, severe infections. Treatment of several hematologic malignancies includes anti-CD20 B cell‑depleting therapy, which is known to cause the development of SHG. Advancements in lymphoma and myeloma management now incorporate bispecific antibody therapies and chimeric antigen receptor T-cell (CAR T-cell) therapies, which have revolutionized care for patients with disease refractory to conventional treatments. However, the risk of SHG is significant, with rates of ≥70% with bispecific antibody treatments and 20–46% with CAR T-cell therapies. Thus, patients with hematologic malignancies have a high rate of SHG attributable to both the underlying disease and associated treatment.