On Saturday 16th June, during the 23rd Congress of EHA (European Hematology Association), Stockholm, Sweden, a poster (PS1471) by Mark Schroeder from Washington University School of Medicine, St. Louis, USA, et al. titled “A phase I/II trial of intravenous azacitidine for acute GvHD prophylaxis in patients undergoing matched unrelated stem cell transplantation: interim phase II results” was presented.
Based on previous studies assessing azacitidine in pre-clinical models, Schroeder and colleagues conducted a phase I/II study to evaluate the safety and efficacy of azacitidine after transplantation for the prevention of acute graft-versus-host disease (aGvHD) and relapse in patients undergoing matched unrelated stem cell transplantation.
Patients and methods:
- Median age = 59 years (range, 24–70)
- N = 35 of 46 patients received transplantation and study drug to date
- Patients received either myeloablative or reduced intensity conditioning without antithymocyte globulin
- Azacitidine was administered IV on Day +7 for five consecutive days and repeated every 28 days for a total of four cycles after allogeneic transplant
- GvHD prophylaxis: mini-methotrexate and tacrolimus
- The recommended phase II dose from phase I: 45 mg/m2
- Median follow up: 248 days (range, 27–891)
- Primary graft failure: one subject related to HHV6 infection
- Median ANC engraftment: 14 days
- Median platelet engraftment: 19 days (range, 10–NR)
- Acute GvHD incidence grade II – IV: 15 patients (43%)
- Acute GvHD incidence grade III/IV: 7 patients (20%)
- Incidence of steroid refractory GvHD: 7 patients
- Four patients have relapsed
- Most common non-hematologic grade 3 or 4 AEs: gastrointestinal toxicity, electrolyte abnormalities, and infections
In summary, azacitidine can be used safely as GvHD prophylaxis starting at day +7 after matched unrelated donor transplantation up to a dose of 45mg/m2. Phase II enrolment and follow up is ongoing.
- Schroeder M. et al. A phase I/II trial of intravenous azacitidine for acute GvHD prophylaxis in patients undergoing matched unrelated stem cell transplantation: interim phase II results. Abstract PS1471. 23rdCongress of the European Hematology Association (EHA).