Incidence of Hypogammaglobulinemia in Patients Receiving Rituximab and the Use of Intravenous Immunoglobulin for Recurrent Infections

Abstract

Rituximab targets normal B cells and tumor B cells. We used a unique data-mining tool to identify patients with lymphoma who were treated with rituximab and who had serial pre and post rituximab immunoglobulin concentrations evaluated. After treatment, 39% (69/179) of patients had low levels of immunoglobulin G. Recurrent sinopulmonary infections were seen in 6.6% (14/211). Intravenous immune globulin appeared to reduce the frequency of infection. Background Rituximab has altered the treatment approach to B-cell malignancies and other diseases. Reports consider that rituximab had limited impact on serum immunoglobulins. However, anecdotes suggest that rituximab can cause symptomatic hypogammaglobulinemia. This retrospective study examined the relationship among rituximab, hypogammaglobulinemia, and treatment of symptomatic hypogammaglobulinemia with intravenous immune globulin (IVIG). Methods Patients with serial quantitative serum immunoglobulin (SIgG) concentrations before and subsequent to rituximab administration at Memorial Sloan-Kettering Cancer Center were identified. Information regarding rituximab administration, SIgG concentrations, frequency of infection, and administration of IVIG were recorded. Results Between December 1998 and April 2009, 211 patients with B-cell lymphoma treated with rituximab and with serial SIgG concentrations were identified. One hundred seventy-nine (85%) patients had normal SIgG before rituximab, 32 (15%) had low SIgG. After rituximab use, hypogammaglobulinemia was identified in 38.54% of patients with initially normal SIgG. The risk was greater in patients who received maintenance rituximab. Symptomatic hypogammaglobulinemia that prompted IVIG administration developed in 6.6% of patients. Conclusions In this data set, rituximab administration was associated with a high frequency of hypogammaglobulinemia, particularly symptomatic hypogammaglobulinemia, among patients who received multiple courses of rituximab. Baseline and periodic monitoring of SIgGs is appropriate in patients who receive rituximab.

Is there a need to redefine the diagnostic criteria for common variable immunodeficiency?

“…Editorial www.expert-reviews.com diseases and lymphomas, there seems to be an increasing number of persistent CVID-like phenotypes remitted for evaluation. This impression is partly supported by recent studies [19,20]. Hypogammaglobulinemia may disappear up to 18 months after cessation of rituximab therapy [21].…”

Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients

“…In any case, it is well known that anti-CD20 treatment is associated with a high frequency of hypogammaglobulinemia and symptomatic hypogammaglobulinemia, and that replacement therapy with IVIg can reduce the incidence of infections in hypogammaglobulinemic patients. 1 In the present study, we excluded from the case series 6 patients with autoimmune disorders treated with immunosuppressive drugs and rituximab, and 2 patients with acute myeloid leukemia who had undergone hematopoietic stem cell transplantation, who developed hypogammaglobulinemia needing Ig replacement therapy. It is important to report that even in these few patients the use of SCIg was effective, safe and well tolerated.…”

“…In particular, anti-CD20 monoclonal antibody (rituximab) is known to be associated with the development of prolonged secondary hypogammaglobulinemia. 1 Long-lasting antibody defects have been reported following rituximab treatment (both in monotherapy or in combination with chemotherapy) in patients with indolent and aggressive B-non-Hodgkin lymphomas (including CLL), [2][3][4] post-transplant Epstein-Barr virus-associated LPDs, [5][6][7][8] postautologous bone marrow transplantation, [9][10][11] and HIV-associated lymphomas. 12 It is worthy of note that the use of rituximab in the setting of non-hematologic conditions (autoimmune cytopenias 13 and rheumatoid arthritis 14 ) has extended the spectrum of secondary hypogammaglobulinemias following anti-CD20 therapy.…”

Therapeutic targeting of the BCR-associated protein CD79b in a TCR-based approach is hampered by aberrant expression of CD79b

“…1,[3][4][5]9 However, side effects of long-term B-cell depletion are manageable, which indicates that B-cell aplasia can be tolerated. [9][10][11][12][13] Although successful in several patients, malignancies refractory to CD20-targeted therapy and the emergence of CD19-negative tumor escape variants after treatment with CD19-targeting CARtransduced T-cells 4 demonstrate the need to identify additional targets for the treatment of B-lineage malignancies. We hypothesized that the B-cell receptor (BCR)-associated protein CD79b presents a suitable target for immunotherapy because CD79b membrane expression is restricted to the B-cell compartment and can be found on many B-cell malignancies.…”