Among some patients with cancer that undergo allogeneic stem cell transplantation (ASCT), azithromycin appears to promote immune cells that allow for disease relapse, according to research published in Blood.

Bronchiolitis obliterans syndrome, a subtype of chronic graft vs host disease (GVHD), is noted in about 10% of ASCT attempts, and is linked with poor clinical outcomes. Although azithromycin has been used to prevent bronchiolitis obliterans post-lung transplantation, a randomized phase 3 trial linked this treatment with a greater risk of relapse-related mortality.

Samples from the randomized ALLOZITHRO trial (ClinicalTrials.gov Identifier: NCT01959100), however, present the opportunity to evaluate the biochemical mechanisms through which azithromycin promotes relapse. For this study, researchers evaluated immune and metabolic function from samples of patients enrolled to ALLOZITHRO to determine how azithromycin increases relapse risk after ASCT.


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The authors relied on multi-omics to evaluate 240 patient samples, of whom 123 were randomly assigned to receive azithromycin whereas 117 received placebo. Other characteristics were balanced on randomization between the 2 groups in the ALLOZITHRO study.

The analysis showed that, compared with placebo, azithromycin was linked with altered energy metabolism pathways and altered immune subsets; these included T cells that exhibited exhausted profiles.

In an in vitro study, azithromycin was also linked with exposure inhibited-T cell cytotoxicity, specifically against tumor cells, as well as glycolysis inhibition with consequently impaired T cell metabolism.

Up-regulation of immunomodulatory genes, including SOCS1, was also noted. “Our results raise the question of the safety of using this treatment in patients at risk of cancer, such as patients with chronic obstructive pulmonary disease,” the authors wrote in their report.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Vallet N, Le Grand S, Bondeelle L, et al. Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation. Blood. 2022;140(23):2500-2513. doi:10.1182/blood.2022016926