New diagnoses of IPSS INT-2/High patients

• Almost all patients will become neutropenic during the first 1-3 cycles of azacitidine therapy
• Therefore consider whether a delay in initiating azacitidine could be acceptable to the patient and clinician. In the AZA-001 registration study, only 52% patients were treated within one year of original diagnosis (which for some, may have been lower-risk). Patients’ management should be assessed by the MDT on an individual basis and then discussed with the patient. Delay may be acceptable for the following groups but this is not an exhaustive list:
  • Patients with relatively well preserved blood counts (e.g. neutrophils >1)
  • Patients with stable blood counts for the preceding 3 months and neutrophils > 1
  • Patients with lower blast count (<10%)
  • Patients lacking good-risk ‘AML’ genetic / genomic characteristics
• If azacitidine therapy deemed immediately necessary, consider using G-CSF and / or antibiotic prophylaxis through cycles 1 & 2 in order to try to prevent hospitalisation with neutropenic sepsis.
  • Where feasible and subject to local guidelines for home administration of azacitidine, consider alternative models of care to minimise hospital attendance for azacitidine injections
  • Blood count monitoring should not be reduced, continuing per local guidelines, but samples taken in the patient’s home where possible and attendance to hospital following, based on local blood product transfusion policy.

Patients already on azacitidine

• Beyond cycle 3, if patients are deemed to be having clinical benefit, consider increasing interval between cycles to 6 weeks, or continuing 4-weekly but reduce to 5 days azacitidine per cycle. Note that there is no trial evidence for a switch from 4-weekly to 6-weekly intervals, but there is some (under-powered) randomised trial evidence that 5-day azacitidine cycles may be less efficacious than 7-day cycles.