What is the recommended treatment regimen for Azacitidine (Azacitidine) in patients with myelodysplastic syndromes (MDS)?

Azacitidine Treatment Regimen for Myelodysplastic Syndromes

For patients with higher-risk MDS who are not immediately eligible for allogeneic stem cell transplantation, azacitidine should be administered at 75 mg/m² subcutaneously daily for 7 consecutive days every 28 days, with at least 6 cycles required to properly evaluate efficacy. 1

Standard Dosing Regimen

Primary Schedule (7-Day Regimen)

• Dose: 75 mg/m² subcutaneously daily 1, 2
• Duration: 7 consecutive days 1
• Cycle frequency: Every 28 days 1, 2
• Route: Subcutaneous injection is the standard route 1

Alternative Schedule (5-2-2 Regimen)

• The "5-2-2" regimen (5 days on, 2 days off, 2 days on) is considered acceptable and often easier to apply in clinical practice 1
• This alternative schedule has not demonstrated survival advantage in higher-risk MDS compared to the 7-day regimen, but is pragmatically acceptable 1

Treatment Duration and Response Assessment

Minimum Treatment Duration

• At least 6 cycles are mandatory before evaluating treatment efficacy, as most patients only respond after several courses 1
• Continue treatment as long as the patient continues to benefit or until disease progression, relapse after response, or unacceptable toxicity 2

Response Criteria

• Complete response (CR) and partial response (PR) are standard endpoints 1
• Hematological improvement (HI) according to IWG 2006 criteria should be considered indicative of response, as it is associated with prolongation of survival compared with supportive care 1
• HI includes improvement in cytopenias across erythroid, platelet, and neutrophil lineages 1

Patient Selection Criteria

Appropriate Candidates

• Higher-risk MDS patients (IPSS-R intermediate, high, or very high risk) without major comorbidities 1
• Patients >70 years or younger patients without a donor for allogeneic stem cell transplantation 1
• Patients ≤70 years without unfavorable karyotype who are not immediately eligible for transplant 1

FDA-Approved Indications

• Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia, thrombocytopenia, or requiring transfusions 2
• Refractory anemia with excess blasts (RAEB) 2
• Refractory anemia with excess blasts in transformation (RAEB-T) 2
• Chronic myelomonocytic leukemia (CMMoL) 2

Dose Modifications

For Frail Patients

• Doses can be reduced in relatively frail patients while maintaining the treatment schedule 1

Monitoring Requirements

• Monitor complete blood counts frequently for anemia, neutropenia, and thrombocytopenia 2
• Monitor patients with renal impairment closely, as azacitidine and metabolites are primarily excreted by the kidneys 2
• Assess baseline risk for tumor lysis syndrome and monitor appropriately 2

Special Clinical Scenarios

Bridge to Transplantation

• 2-6 cycles of azacitidine are commonly used before hematopoietic stem cell transplantation to reduce bone marrow blasts or for logistical reasons 1
• Fit patients ≤70 years with a donor should proceed to allogeneic stem cell transplantation, preceded or not by azacitidine 1

Supportive Care

• Premedicate for nausea and vomiting 2
• Do not substitute azacitidine for injection for oral azacitidine, as indications and dosing differ 2

Common Pitfalls to Avoid

• Do not discontinue treatment before 6 cycles unless there is clear disease progression or unacceptable toxicity, as delayed responses are common 1
• Do not use 5-day regimens as standard in higher-risk MDS without understanding they have not demonstrated survival advantage compared to the 7-day regimen 1
• Do not withhold treatment in patients with baseline cytopenias, as the recommended starting dosage applies to all patients regardless of baseline hematology values 2