The French phase III ALLOZITHRO trial, stopped early due to excessive hematologic relapse in the azithromycin group, showed worse airflow decline–free survival with azithromycin vs placebo after hematopoietic stem cell transplantation (HSCT) for hematologic malignancy. The study findings were reported by Anne Bergeron, MD, PhD, of Hôpital Saint-Louis, Paris, and colleagues in JAMA. Prior studies had suggested that azithromycin might reduce the risk of post–lung transplant bronchiolitis obliterans syndrome.
In the double-blind trial, 480 patients were randomized to receive azithromycin at 250 mg (n = 243) or placebo (n = 237) 3 times per week for 2 years starting with the administration of the conditioning regimen. Patients were enrolled between February 2014 and August 2015, with follow-up through April 2017. The primary efficacy endpoint was airflow decline–free survival at 2 years after randomization.
At 13 months after the end of enrollment, the independent data and safety monitoring board detected an imbalance in hematologic relapse between the groups, and treatment was stopped in December 2016. Among 480 randomized participants, 465 were included in the modified intention-to-treat analysis.
At data cutoff, 104 patients (22%; 54 azithromycin vs 50 placebo recipients) had experienced airflow decline, and 138 had died (30%; 78 azithromycin vs 60 placebo recipients). Two-year airflow decline–free survival was 32.8% in the azithromycin group vs 41.3% in the placebo group (unadjusted hazard ratio [HR] = 1.3, P = .03). Bronchiolitis obliterans syndrome occurred in 6% vs 3% of patients (P = .08). Two-year overall survival was 56.6% vs 70.1% (unadjusted HR = 1.5, P = .02). In post hoc analysis, the 2-year cumulative incidence of hematologic relapse was 33.5% vs 22.3% (unadjusted HR = 1.7, P = .002).
The investigators concluded: “Among patients undergoing allogeneic HSCT for hematological malignancy, early administration of azithromycin resulted in worse airflow decline–free survival than did placebo; these findings are limited by early trial termination. The potential for harm related to relapse requires further investigation.” ■