Administration of azithromycin beginning at the time of conditioning in patients undergoing allogeneic hematopoietic stem cell transplant resulted in worse airflow decline–free survival than did placebo, according to findings from the randomized ALLOZITHRO trial.
The 2-year airflow decline–free survival rate was 32.8% in 243 patients who received 250 mg of azithromycin for 2 years, compared with 41.3% in 237 who received placebo (hazard ratio, 1.3), Anne Bergeron, MD, of Hopital Saint-Louis, Paris, and her colleagues reported in the Aug. 8 issue of JAMA.
Further, of 22 patients who experienced bronchiolitis obliterans syndrome, 15 were in the azithromycin group, compared with 7 in the placebo group, and 2-year mortality was increased in the azithromycin group (56.6% vs. 70.1%; hazard ratio, 1.5) the investigators noted (JAMA. 2017 Aug 8;318:557-66. doi: 10.1001/jama.2017.9938).
A post hoc analysis showed that the 2-year cumulative incidence of hematological relapse was 33.5% with azithromycin vs. 22.3% with placebo; the trial was terminated early because of this unexpected finding.
Although prior studies have suggested that azithromycin may reduce the incidence of post–lung transplant bronchiolitis obliterans syndrome, which has been shown to increase morbidity and mortality after allogeneic HSCT, the findings of this parallel-group trial conducted in 19 French transplant centers between February 2014 and August 2015 showed a decrease in survival and an increase in hematological relapse at 2 years with azithromycin vs. placebo. The findings, however, are limited by several factors – including the trial’s early termination – and require further study, particularly of the potential for harm related to relapse, the investigators concluded.
The ALLOZITHRO trial (NCT01959100) was funded by the French Cancer Institute, Oxygene, and SFGM-TC Capucine. Dr. Bergeron reported receiving unrestricted research grant funding for the trial from the French Ministry of Health, SFGM-TC Capucine association, and SOS Oxygene; receiving speaker fees from Merck, Gilead, and Pfizer; and serving on the advisory board of Merck.