Immune Globulin and Prophylactic Antibiotics Provide Similar Efficacy in Treating Hypogammaglobulinemia Secondary to Hematological Malignancy

Immune globulin replacement and prophylactic antibiotics are commonly used to prevent infections in patients with secondary hypogammaglobulinemia due to hematological malignancies but have never been directly compared. 

A randomized controlled feasibility trial conducted in seven hospitals in Australia and New Zealand enrolled patients with secondary hypogammaglobulinemia with either a history of recurrent/severe infection or an immunoglobulin G level <4 g/L. Participants were randomized in a 1:2 ratio to immune globulin (0.4 g/kg per 4 weeks IV) or daily antibiotics (trimethoprim-sulfamethoxazole 160 mg/800 mg or, if contraindicated, 100 mg doxycycline) for 12 months. Participants allocated to antibiotics were allowed to crossover after grade ≥3 infections. 

The primary outcome was proportion of patients alive on the assigned treatment 12 months after randomization. Between August 2017 and April 2019, 63 patients were randomized: 42 to antibiotics and 21 to immune globulin. Proportion of participants alive on allocated treatment at 12 months was 76 percent in the immune globulin and 71 percent in the antibiotic arm (Fisher exact test P=.77; odds ratio, 0.78; 95% CI, 0.22-2.52). The lower quartile for time to first major infection (median, not reached) was 11.1 months for the immune globulin and 9.7 months for the antibiotic arm (log-rank test, P=.65). Three participants in the immune globulin and two in the antibiotic arm had grade ≥3 treatment-related adverse events. A similar proportion of participants remained on antibiotic prophylaxis at 12 months to those on immune globulin, with similar rates of major infections.

The researchers concluded that their findings support the feasibility of progressing to a Phase III trial.