medwireNews: A study investigating whether azithromycin improves airflow decline–free survival following allogeneic hematopoietic stem cell transplantation (HSCT) was terminated early due to an unexpected increased risk for hematologic malignancy relapse, researchers report.
The ALLOZITHRO parallel-group trial, conducted in 19 French academic transplant centers, randomly assigned 465 patients (mean age, 52 years; 35% women) who had received an allogeneic HSCT for a hematologic malignancy to receive either azithromycin 250 mg (n=234) or placebo (n=231) three times per week for 2 years, starting at the same time as the conditioning regimen.
The researchers found that, at the time of data cutoff, 54 (23.1%) patients receiving azithromycin and 50 (21.6%) receiving placebo had experienced an airflow decline, while 78 (33.3%) in the former group and 60 (26.0%) in the latter group had died.
At 2 years, the rate of airflow decline–free survival was significantly lower with azithromycin than with placebo, at 32.8% versus 41.3%.
In line with this, there were more cases of bronchiolitis obliterans syndrome in the azithromycin group than in the placebo group (15 vs 7), but the difference was not statistically significant.
However, writing in JAMA, Anne Bergeron (Hôpital Saint-Louis, Paris, France) and fellow ALLOZITHRO study investigators say that their findings were “limited by the early trial termination.”
They explain: “Thirteen months after enrollment, the independent data and safety monitoring board detected an unanticipated imbalance across blinded groups in the number of hematological relapses, and the treatment was stopped.”
Indeed, a post-hoc analysis showed that, after adjustment for factors associated with relapse, patients receiving azithromycin had a significant 60% increased risk for hematologic relapse at 2 years compared with those receiving placebo.
At 2 years, the cumulative incidence of hematologic relapse was 33.5% with azithromycin versus 22.3% with placebo.
Patients in the azithromycin group also had a significant 30% increased risk for death at 2 years, with a 2-year survival rate of 56.6% versus 70.1% in the placebo group.
Bergeron et al say that the adverse outcomes they observed “require further investigation,” but also note that a tipping-point analysis, conducted to assess the effect of early termination of the study, found that “the primary end point findings could not be reversed to demonstrate a beneficial effect of azithromycin.”
They conclude: “Overall, the results of this study suggest it is unlikely that azithromycin could reduce the risk of bronchiolitis obliterans syndrome after allogeneic HSCT.”
By Laura Cowen
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