TCT Meeting 2019 | Azithromycin for the management of moderate to severe chronic graft-versus-host disease

On 21 February 2019, Dr. Mark Shamoun from the University of Michigan Medical Center, Ann Arbor, MI, USA, presented data from a retrospective, single-center study assessing relapse rates in a cohort of patients receiving azithromycin for moderate to severe chronic graft-versus-host disease (cGvHD) at the 2019 TCT Transplantation and Cellular Therapy Meetings of ASBMT and CIBMTR in Houston, Texas, USA. The US Food and Drug Administration (FDA) safety warning in August 2018, raised concerns on the risk of relapse in patients receiving azithromycin as prophylaxis for bronchiolitis obliterans syndrome (BOS) following allogeneic hematopoietic cell transplant (allo-HCT).

Patients and methods:

• The allo-HCT database, at the University of Michigan, included n = 239 patients between 2010 and 2017
• Median age = 55 years (range, 4–72)
• Diagnosis: moderate-severe cGvHD
• Patients were divided into two groups:
  • Patients receiving an extended course of azithromycin (≥ 14 days) for cGvHD management (cohort 1, n = 86)
  • Patients who did not receive an extended course of azithromycin (cohort 2, n = 153): patients in this cohort either did not receive any azithromycin (n = 122) or had received an abbreviated (< 14 day) course (n = 31) of azithromycin post-allo-HCT

Key findings:

All data is given as cohort 1 vs cohort 2

• Patients exhibiting BOS: 100% vs < 5%
• Rates of cGvHD:
  • Moderate: 22% vs 49%
  • Severe: 78% vs 51%
• Median time to commencement of azithromycin post-allo-HCT (cohort 1): 15 months (range, 3–68)
• Median duration of azithromycin therapy (cohort 1): 26 months (range, 1–77)
• Two-year cumulative incidence of relapse: 2% (95% CI, 1–9) vs 16% (95% CI, 11–23), P = 0.001
• Two-year relapse rate: 4.0% (95% CI, 1.0–9.0) vs 17.0% (95% CI, 11.0–23.0), P = 0.001
• Relapse rates post allo-HCT: 7/86 (8.1%) patients vs 28/153 (18.3%) patients
• Median time to relapse: 876 days (range, 379–1303) vs 371 days (range, 98–1252)
• Two-year overall survival: 93% (95% CI, 88–99) vs 78% (95% CI, 72–85), P = 0.003

In summary, administration of azithromycin for the treatment of moderate to severe cGvHD was not associated with an increased risk of relapse in patients undergoing allo-HCT. Furthermore, Dr. Mark Shamoun concluded that azithromycin therapy for patients with cGvHD should not be contra-indicated, as this study has illustrated that azithromycin is safe for patients with BOS post-allo-HCT.