Prophylactic antibiotics could be an alternative to immunoglobulin replacement for secondary hypogammaglobulinaemia due to blood cancer, with an Australian study showing a similar proportion of patients alive at 12 months.
Findings also showed a similar rate of major infection and adverse events.
The randomised controlled feasibility trial involved 63 patients with acquired hypogammaglobulinaemia with either a history of recurrent/severe infection or an immunoglobulin G level less than 4 g/L who were randomised in a 1:2 ratio to receive immunoglobulin (n = 21) or daily antibiotics (n = 42) for 12 months.
The trial was conducted at seven hospitals in Australia and New Zealand. Participants (mean age 70, 54% female) mostly had chronic lymphocytic leukaemia (46%), multiple myeloma (19%) and non-Hodgkin lymphoma (32%).
The immunoglobulin group received 0.4 g/kg dose every four weeks via IV or a 100 mg/kg dose per week subcutaneously.
The antibiotics group received trimethoprim-sulfamethoxazole 160 mg/800 mg once daily or, if contraindicated, 100 mg doxycycline.
Nine patients on antibiotics were allowed to crossover with a grade ≥3 infection.
The proportion of participants alive on allocated treatment at 12 months was 76% in the immunoglobulin arm and 71% in the antibiotic arm (OR: 0.78), data showed.
While the median time points for time to first major infection (grade ≥3 infection) were not reached in either treatment arm, the lower quartile was 11.1 months and 9.7 months for the immunoglobulin group and antibiotic group, respectively.
The lower quartile for time to first microbiologically confirmed infection was 6.3 months in the immunoglobulin arm and not reached in the antibiotic arm.
Clinically documented infections averaged 1.86 and 1.33 per participant in the immunoglobulin arm and in the antibiotic arm, respectively. Microbiologically confirmed infections averaged 0.52 and 0.38 per participant, respectively.
The researchers said there were two deaths in the immunoglobulin group within 12 months, including one infection-related death. One death occurred in the antibiotic group after 12.3 months following the report of a major infection at 11.7 months.
The number of treatment-related adverse events were similar between the groups.
Writing in Blood Advances [link here], the authors, led by consultant haematologist Professor Zoe McQuilten of Monash University, Melbourne, said the findings supported the feasibility of progressing to a phase 3 trial.
“In Australia, the demand for Ig has increased by >10% per year over the last decade, and patients with haematological malignancies are the largest single group using Ig products. There are considerable costs of providing Ig replacement,” they wrote.
“For example, based on the published cost of domestic IV Ig in Australia, the annual product cost for a 70 kg individual is around $21, 372 Australian dollars. Furthermore, there are barriers in countries to manufacture Ig preparations in order to achieve self-sufficiency for plasma products, including sufficient domestic plasma collection, cost, and access to commercial or not-for-profit manufacturers.
“Therefore, there is a pressing need to generate contemporary data regarding the comparative effectiveness and safety of Ig replacement in this patient population.”