Efficacy of Bortezomib for Treating Anti-Interferon-Gamma Autoantibody-Associated Adult-Onset Immunodeficiency Syndrome.

backgroundCurrently, there is no effective treatment for adult-onset immunodeficiency (AOID) syndrome with anti-interferon-gamma autoantibodies (anti-IFN-γ-auto-Abs). This study aimed to investigate the effectiveness of bortezomib (BTZ) for decreasing anti-IFN-γ-auto-Abs.

methodsA pre- and post-intervention study was conducted from February 2017 through June 2019 at Siriraj Hospital (Bangkok, Thailand). Five patients were invited to receive once-weekly BTZ (1.3 mg/m2 body surface area) subcutaneously for 8 weeks followed by oral cyclophosphamide (1 mg/kg/d) for 4 months. The primary outcomes were the difference in antibody level at 8 and 48 weeks compared with baseline and the incidence of serious adverse events (AEs). The secondary outcome was the occurrence of opportunistic infections (OIs) during the 72 weeks after starting BTZ.

resultsThe median patient age was 46 years (range, 34-53). All patients had 3-5 OIs prior to enrollment. All patients were receiving antimycobacterial agents for treatment of nontuberculous mycobacterial infection at enrollment. There was no significant difference in the mean optical density of auto-Abs at 8 weeks (3.73 ± 0.72) or 48 weeks (3.74 ± 0.53) compared with baseline (3.84 ± 0.49; P = .336 and P = .555, respectively). However, after serum dilution, the antibody titer nonsignificantly decreased 8-16 weeks after BTZ initiation (P = .345). Ten OIs were observed 24-72 weeks after BTZ initiation.

conclusionsTreatment with BTZ followed by cyclophosphamide yielded no significant decrease in antibody titer levels, and 10 OIs were observed during 24-72 weeks of BTZ treatment. No serious AEs were observed. Combining rituximab with BTZ is likely necessary to prevent generation of new autoantibody-producing plasma cells. Clinical Trials Registration. NCT03103555.