EBMT 2019 | Prevention of relapse following allogeneic stem cell transplantation using azacitidine in patients with high-risk AML

For patients with acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-SCT) can be a curative approach, however, relapse is a common cause of treatment failure.¹ The use of azacitidine has shown efficacy in patients ineligible for standard chemotherapy. However, there is limited data on the use of azacitidine in the post allo-SCT setting for patients with AML.²

On 26 March 2019, at the 45^th Annual Meeting of the European Society for Blood and Marrow Transplantation, Dr. Ivetta Danylesko, from the Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, IL, discussed the use of low-dose azacitidine as a therapeutic strategy to prevent and treat relapse following allo-SCT in patients with AML or myelodysplastic syndrome (MDS).³

Patient characteristics and treatment schedule:

• Patients with AML or MDS (n = 66 [AML]; n = 28 [MDS]; median age = 64 years; range, 24–77), in complete remission (CR) following allo-SCT received low-dose azacitidine (32 mg/m² for 5 days in a 28-day cycle, planned for two-years)
• In patients with overt relapse following allo-SCT, azacitidine (32–75 mg/m²) was given for 5–7 days until progression
• For the combined prophylactic/pre-emptive treatment group, median number of azacitidine courses: 8 (range, 1–50)
• For the active disease group, median number of azacitidine courses: 3 (range, 2–36)

Key findings:

• In patients receiving prophylactic azacitidine (n = 22), seven patients had active disease prior to allo-SCT
  • Patients with active disease who failed to achieve CR with induction and salvage therapy: 4/7
  • Patients remaining in CR: 17/22
• Patients receiving pre-emptive azacitidine following allo-SCT: 19
  • Patients achieving CR: 16/19
  • Patients remaining in CR: 10/19
• Patients receiving azacitidine due to relapse status following allo-SCT: 53
  • Median follow-up time: 15 months (3–43)
  • Patients achieving CR: 10/53
  • Patients with stable disease: 10/53
  • Patients with progressive disease: 33/53
  • Estimated three-year overall survival (OS): 17% (95% CI, 5–29)
  • Estimated three-year progression-free survival (PFS): 7% (95% CI, 0–13)
  • Rate of pancytopenia: 89% (47/53 patients)
  • Patients experiencing infections during azacitidine therapy: 79% (42/53)
• For patients in the prophylactic and pre-emptive therapy groups (n = 41)
  • Median time from allo-SCT to initiation of azacitidine: 2.4 months (range, 1.2–14.9)
  • Median follow-up time: 14 months (range, 3–39)
  • Estimated three-year OS: 58% (95% CI, 29–86)
  • Estimated three-year PFS: 50% (95% CI, 27–74)
  • Rate of pancytopenia: 51% (21/41 patients)
  • Patients experiencing infections during azacitidine therapy: 41% (17/41)
• In the total population, the rate of graft-versus­-host disease (GvHD) prior to azacitidine therapy: 31% (29/94 patients)
• In the total population, the rate of GvHD during azacitidine therapy: 47% (44/94 patients)

Dr. Danylesko concluded that for prophylactic treatment in high-risk patients with AML and MDS, or the preventive treatment of relapse following allo-SCT, azacitidine is an effective and safe therapeutic regimen. Moreover, the use of low-dose azacitidine in the maintenance setting post allo-SCT needs further exploration.