Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial

Bergeron A, Chevret S, Granata A, et al. JAMA 2017;318(6):557-566. [CrossRef] [PubMed]

Bronchiolitis obliterans syndrome has been associated with increased morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT). Previous studies have suggested that azithromycin may reduce the incidence of post-lung transplant bronchiolitis obliterans syndrome presumably through an anti-inflammatory effect. The ALLOZITHRO parallel-group trial conducted in 19 French academic transplant centers and involving participants who had undergone allogeneic HSCT for a hematological malignancy. Patients were randomly assigned to receive 3 times a week either 250 mg of azithromycin (n = 243) or placebo (n = 237) for 2 years, starting at the time of the conditioning regimen. Thirteen months after enrollment, the independent data and safety monitoring board stopped the trial. At the time of data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo) had experienced an airflow decline; 138 patients (30%) died (78 azithromycin vs 60 placebo). The azithromycin group had increased mortality, with a 2-year survival of 56.6% (95% CI, 50.2%-63.7%) vs 70.1% (95% CI, 64.2%-76.5%) in the placebo group (unadjusted HR, 1.5; 95% CI, 1.1-2.0; P = .02). In a post hoc analysis, the 2-year cumulative incidence of hematological relapse was 33.5% (95% CI, 27.3%-39.7%) with azithromycin vs 22.3% (95% CI, 16.4%-28.2%) with placebo (unadjusted cause-specific HR, 1.7; 95% CI, 1.2-2.4; P = .002). The FDA recently issued a warning against using chronic azithromycin therapy in HSCT.