Controversies about immunoglobulin replacement therapy in HSCT recipients with hypogammaglobulinemia

Abstract

The efficacy of immunoglobulin replacement therapy (IgRT) has been demonstrated for primary immune deficiency diseases and hematological malignancies such as chronic lymphocytic leukemia (CLL) or multiple myeloma with hypogammaglobulinemia. Clinical development of anti-B cell therapies including a monoclonal antibody, bispecific antibody, or chimeric antigen receptor T-cell therapy which could result in severe hypogammaglobulinemia accelerates the argument of prophylactic use of IgRT. Clinical guidelines for CLL describe immunoglobulin administration in patients with a low IgG who have experienced a severe/repeated bacterial infection. The utility in hematopoietic stem-cell transplantation (HSCT) remains unknown. Although an early randomized trial demonstrated that IgRT decreased infection risk and transplant-related mortality after HSCT, subsequent clinical trials could not validate the benefit. Consequently, a meta-analysis did not show the benefit of IgRT in HSCT. Most of the available data derives from matched-related HSCT using myeloablative regimen, and the impact in haploidentical and cord blood transplantation, or reduced-intensity HSCT remains unknown. One crucial issue is that no studies exist for patients with only hypogammaglobulinemia after HSCT. Other challenges are heterogeneous patient characteristics, or immunoglobulin formulation, dosage, schedule, route and duration of IgRT. Without evidence in HSCT, it would be reasonable to follow the guidelines for other diseases with hypogammaglobulinemia.

Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy

“…4. Immunoglobulin replacement: Data on immunoglobulin replacement in CAR T-cell therapy is extrapolated from patients with hematologic malignancy who receive anti-CD20 monoclonal antibody and patients who undergo allogeneic HSCT [96][97][98][99]. Therefore, it is unclear if IVIG replacement alters the overall post-CAR T-cell IgG level or improves survival outcomes [96,100].…”

A single‐institution pre–post comparison of subcutaneous immunoglobulin replacement therapy in allogeneic haematopoietic cell transplantation recipients

“…Data on ScIgRT in the field of allo-HCT are limited, as reviewed previously. 15 In a recent small study, ScIg was administered to allo-HCT patients for up to 6 months, with no statistically significant benefit in clinical outcomes but an advantage in terms of patient satisfaction and healthcare costs. 21 The small number of patients and short duration of intervention in that pilot study may have been insufficient to assess the incidence and severity of infections.…”

“…[11][12][13][14] However, it is not well established whether hypogammaglobulinaemia in allo-HCT recipients affects clinical outcomes, including the incidence of infectious diseases. 15 One prospective RCT revealed the marked utility of IgRT in allo-HCT. 16 Although other studies also assessed the beneficial impact of IgRT after allo-HCT, meta-analyses showed no consistent benefit to using IgRT after allo-HCT.…”

“…There is still controversy regarding IgRT after allo-HCT, although several guidelines, including those of the National Comprehensive Cancer Network (NCCN), recommend its use in patients with hypogammaglobulinaemia who have a history of infectious disease after allo-HCT. 15 In clinical practice, IgRT is currently used in allo-HCT patients at the discretion of the institution or attending physician according to their IgG level and history of infectious disease. Subcutaneous IgRT (ScIgRT) is an option that is commonly used in the field of PID.…”

“…Prospective randomized controlled trials (RCTs) demonstrated the clear clinical benefit of immunoglobulin replacement therapy (IgRT) in SID associated with CLL and MM 11–14 . However, it is not well established whether hypogammaglobulinaemia in allo‐HCT recipients affects clinical outcomes, including the incidence of infectious diseases 15 . One prospective RCT revealed the marked utility of IgRT in allo‐HCT 16 .…”