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Published on: November 26, 2018
Subcutaneous immunoglobulin replacement for treatment of humoral immune dysfunction in patients with chronic
S Shahzad Mustafa1,2, Saad Jamshed3, Karthik Vadamalai4
1Division of Allergy, Immunology, Rheumatology, Rochester Regional Health, Rochester, New York, United States of America.
Insights
Patients with chronic lymphocytic leukemia (CLL) often have humoral immunodeficiency. Subcutaneous immunoglobulin (SCIG) therapy effectively improved immunoglobulin levels and reduced infections in a study of CLL patients.
Area of Science:
- Immunology
- Hematology
- Pharmacology
Background:
- Patients with chronic lymphocytic leukemia (CLL) frequently experience hypogammaglobulinemia and non-neutropenic infections.
- This study investigated humoral immunodeficiency in CLL patients with elevated IgG levels (≥ 400 mg/dL).
Purpose of the Study:
- To determine the prevalence of humoral immunodeficiency in CLL patients with serum IgG ≥ 400 mg/dL.
- To evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this specific patient population.
Main Methods:
- Assessed serum IgG, IgM, and IgA levels.
- Measured pre/post-vaccine IgG titers for diphtheria, tetanus, and Streptococcus pneumoniae.
- Treated patients with evidence of humoral dysfunction using SCIG (Hizentra) for 24 weeks.
Main Results:
- 93.3% of patients demonstrated humoral immunodeficiency based on suboptimal vaccine responses.
- SCIG treatment increased median serum IgG levels and specific IgG to Streptococcus pneumoniae.
- Non-neutropenic infections decreased significantly during SCIG therapy.
Conclusions:
- CLL patients with IgG > 400 mg/dL exhibit humoral immunodeficiency.
- SCIG is well-tolerated and effective in improving IgG levels and reducing infections in these patients.
- SCIG may decrease the need for antibiotics in managing non-neutropenic infections in CLL.
Background:
Patients with chronic lymphocytic leukemia (CLL) experience hypogammaglobinemia and non-neutropenic infections. In this exploratory proof of concept study, our objective was to determine the prevalence of humoral immunodeficiency in patients with CLL and serum IgG ≥ 400 mg/dL, and to evaluate the efficacy of subcutaneous immunoglobulin (SCIG) in this population.
Patients And Methods:
Patients with CLL with serum IgG ≥ 400 mg/dL were evaluated for serum IgG, IgM, IgA, along with pre/post vaccine IgG titers to diphtheria, tetanus, and Streptococcus pneumoniae. Patients with evidence of humoral dysfunction were treated with SCIG with Hizentra every 7±2 days for 24 weeks.
Results:
Fifteen patients enrolled with median IgG = 782 mg/dL [IQR: 570 to 827], and 6/15 (40%) responded to vaccination with Td, while 5/15 (33%) responded to vaccination with PPV23. 14/15 (93.3%) demonstrated humoral immunodeficiency as evidenced by suboptimal vaccine responses, and were treated with SCIG. In patients treated with SCIG, serum IgG increased from 670 mg/dL [IQR: 565 to 819] to 1054 mg/dL [IQR: 1040 to 1166] after 24 weeks (95% CI: 271-540). For streptococcus pneumoniae, the median protective serotypes at baseline was 8 [IQR: 4 to 9] and increased to 17 [IQR: 17 to 19] after 24 weeks (95% CI: 6.93-13.72). Non-neutropenic infections (NNI) decreased from 14 to 5 during treatment with SCIG.
Conclusions:
Patients with CLL demonstrate humoral immunodeficiency despite IgG > 400 mg/dL. For these patients, SCIG is well tolerated and efficacious in improving serum IgG, specific IgG to streptococcus pneumoniae, and may decrease reliance on antibiotics for the treatment of NNIs.
Clinical Trials Registration:
NCT03730129.
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