Should treatment of hypogammaglobulinemia with immunoglobulin replacement therapy (IgRT) become standard of care in patients with chronic lymphocytic leukemia?

Abstract

Hypogammaglobulinemia (HGG) is a frequent finding in patients with hematological malignancies, and is commonly described in chronic lymphocytic leukemia (CLL) before or after treatment. We reviewed published literature available online in the last thirty years through Medline search of indexed articles focusing on the main differences and advantages of the products now available on the market, namely intravenous Ig (IVIg) and subcutaneous Ig (SCIg) preparations. IgRT is effective and safe in the prophylaxis of infections in a selected group of patients with CLL and hypogammaglobulinemia and is therefore a valuable tool for clinicians in the everyday management of infectious risk. We encourage the use of SCIg formulations as they appear to have similar efficacy but better cost-effectiveness and tolerability.

Comparison of the blood immune repertoire with clinical features in chronic lymphocytic leukemia patients treated with chemoimmunotherapy or ibrutinib

“…This key clinical correlate likely provides much insight into the increased susceptibility to infections, including COVID-19, regardless of vaccination, documented in this study comparing two clinically effective regimens. A recent study by Noto, et al., endorsed intravenous or subcutaneous immunoglobulin replacement in CLL patients with hypogammaglobulinemia to manage increased infection risk ( 69 ). While current therapies may be efficacious in targeting leukemic B cells and restoring T, NK, monocyte, and dendritic cells, failure to reconstitute functional conventional B cells and humoral immunity, will maintain the immunocompromised state in CLL patients ( 3 , 10 ).…”

Clinical efficacy of prophylactic intravenous immunoglobulin for elderly DLBCL patients with hypogammaglobulinemia in the COVID-19 pandemic era

“…Moreover, during B cell–depleting therapies such as rituximab, over 30% of patients with B-cell lymphoma newly develop some form of immunoglobulin deficiency ( 14 ). Hypogammaglobulinemia, characterized by reduced serum immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM) levels, is commonly observed in chronic lymphocytic leukemia (CLL) with an incidence ranging from 20% to 70% ( 16 ). IgM is a critical primary responder to viral pathogens causing major pandemics, and IgG responses are fundamental to adaptive immunity ( 17 , 18 ).…”

“…Previous research on CLL has highlighted the significant association between hypogammaglobulinemia and an increased risk of infectious events, a primary cause of death. Thus, patients with CLL with hypogammaglobulinemia might benefit from antibody replacement therapy using IVIG ( 16 ). Similarly, patients with hypogammaglobulinemia undergoing immunochemotherapy for DLBCL experience higher rates of severe infections, indicating potential benefits of IVIG for infection prevention ( 13 , 25 ).…”

Severe Fatal Mucormycosis in a Patient with Chronic Lymphocytic Leukaemia Treated with Zanubrutinib: A Case Report and Review of the Literature

“…It is usually a non-reversible phenomenon that increases the risk of infection. Infections are still the main cause of death among patients with CLL, accounting for 25–50% of the mortality rate in these patients [ 8 , 9 ]. The abovementioned immune dysregulation is further worsened by medical treatments, such as not chemoimmunotherapy, but also Bruton’s tyrosine kinase (BTK) inhibitors.…”