Washington, D.C.—Lung issues are a known risk of stem cell transplants used to prolong life in some cancer patients.

For example, the Fred Hutchinson Cancer Research Center in Seattle estimates that 30% to 60% of all hematopoietic stem cell transplant (HSCT) patients develop some type of posttransplant lung problem. Those could be infections, such as aspergillus or cytomegalovirus (CMV), or noninfectious problems such as bronchiolitis obliterans syndrome (BOS) and bronchiolitis obliterans organizing pneumonia (BOOP).

Now, the FDA is warning that the antibiotic azithromycin, marketed as Zithromax and Zmax, should not be prescribed long-term to prevent BOS  in patients with cancers of the blood or lymph nodes who undergo a donor stem cell transplant.

The FDA points to results of a clinical trial that found an increased rate of relapse in cancers affecting the blood and lymph nodes and a higher risk of death. The agency says it is reviewing additional data and will communicate their conclusions and recommendations when our review is complete.

BOS is caused by inflammation and scarring in the airways of the lungs, resulting in severe shortness of breath and dry cough. The manufacturer of brand name azithromycin is providing a “Dear Healthcare Provider” letter on the safety issue to clinicians who treat patients undergoing donor stem cell transplants.

The study cited by the FDA, the ALLOZITHRO Randomized Clinical Trial, included 465 patients. Results published last year in JAMA determined that 2-year airflow decline–free survival was significantly worse for the azithromycin group than for the placebo group (hazard ratio, 1.3). In fact, the trial was terminated early because of a significantly increased risk in the azithromycin group of hematological relapses, which was a nonprespecified adverse event.

Azithromycin, which has been on the market for more than a quarter century, is not FDA-approved for preventing bronchiolitis obliterans syndrome.

In fact, the FDA emphasized that no known effective antibiotic treatments for prophylaxis of BOS are available and that healthcare professionals should not prescribe long-term azithromycin for that purpose in patients who undergo donor stem cell transplants.

The agency also advises that patients who have had a stem cell transplant should not stop taking azithromycin without first consulting with their prescriber.

Researchers halted the ALLOZITHRO trial about 13 months after the study completed enrollment of 480 patients because an unexpected increase in the rate of both cancer relapses and death was observed in patients taking azithromycin.

Specifically, cancer relapse was observed in 77 patients (32.9%) with azithromycin treatment compared to 48 patients (20.8%) with placebo. Overall, 95 patients died in the azithromycin treatment group versus 66 patients in the placebo group. That made the 2-year survival rate 56.6% in azithromycin-treated patients compared to 70.1% in those receiving a placebo.

In the first few months of the trial, the death rate was about equal between those receiving azithromycin.
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