A Retrospective Study on the Efficacy of Subcutaneous Immunoglobulin as Compared to Intravenous Formulation in Patients with Chronic Lymphocytic Leukemia and Secondary Antibody Deficiency

Abstract

Secondary antibody deficiency (SAD) is a common complication in chronic lymphocytic leukemia (CLL) which favors the development of life-threatening infections. Subcutaneous immunoglobulins (IG) (SCIG) have been proven to be as effective as intravenous immunoglobulin (IVIG) in primary immunodeficiencies. Since only a few studies investigated SCIG in secondary antibody deficiency, the aim of this study was to assess the efficacy and safety of SCIG or IVIG in CLL patients with secondary antibody deficiency. One hundred and sixteen CLL patients were recruited, 63% were males, and the median age was 68 years; 44% had bronchiectasis and 76% never smoked. Forty-nine patients received IVIG and 88 SCIG, including 28 patients who shifted from IVIG to SCIG. Despite similar baseline IgG levels, patients receiving SCIG achieved higher IgG after at least +6 months (p = 0.0009). We observed that SCIG can decrease the cumulative incidence of first (HR 0.39 p < 0.0001) and second (HR 0.56 p = 0.0411) infection more than IVIG. The effect was remarkable in that patients were able to reach at least 6 g/L of IgG after 6 months of treatments (p < 0.0001). Replacement therapies were well tolerated with less adverse events and a lower discontinuation rate in patients was managed with SCIG than IVIG. In this study we describe the clinical features of a large cohort of CLL with secondary antibody deficiency receiving IG. We demonstrated that SCIG are active and well tolerated drugs that allows to reach higher IgG levels and decrease the rate of infections better than IVIG, in particular when IgG levels reach 6 g/L.

Keywords: chronic lymphocytic leukemia; intravenous immunoglobulin; replacement therapy; secondary immunodeficiency; subcutaneous immunoglobulin.

Figure 1

Histograms of IgG levels and infection rates. In the upper panel (A) there is a histogram reporting the serum IgG levels at baseline, after 3, 6 and 12 months of intravenous immunoglobulins (IVIG) or subcutaneous immunoglobulin (SCIG). Kruskal–Wallis test was used to analyse IgG levels in patients receiving IVIG and SCIG at different time points. Mann–Whitney test was used to compare IgG at same time point between patients receiving IVIG and SCIG. SCIG allowed patients to reach higher IgG trough levels than IVIG after at least 6 months of treatment. In particular, at month +6, IgG > 6 g/L was achieved by 33.2% and 52.3% of patients with IVIG and SCIG (p = 0.0322), respectively. In the lower panel (B) are shown the rates, expressed as events/person/year, of all infections and grade ≥ 3 (G3) events before and after IVIG and SCIG.

Figure 2

Cumulative incidence of infections and discontinuation. The upper panel on the left (A) shows the Kaplan–Meier curves of time to first infection in patients treated with intravenous immunoglobulins (IVIG) or subcutaneous immunoglobulin (SCIG). The upper panel on the right (B) shows the Kaplan–Meier curves of time to first infection in patients IVIG or SCIG, according to serum IgG levels. Patients achieving at least 6 g/L of IgG display a longer time to the first infection. In the lower-left panel (C) is shown the Kaplan–Meier curves of time to second infection in patients treated with IVIG or SCIG. In the lower-right panel (D) is shown the Kaplan–Meier of the cumulative incidence of discontinuation in patients treated with IVIG or SCIG. Log-rank test was used to compared survival curves.