What is the recommended use of Inqovi (cedazuridine and decitabine) for myelodysplastic syndromes?

Recommended Use of Inqovi (Cedazuridine and Decitabine) for Myelodysplastic Syndromes

Inqovi (cedazuridine/decitabine) is recommended for adults with intermediate and higher-risk MDS, including previously treated and untreated, de novo and secondary MDS with various French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and CMML) in intermediate-1, intermediate-2, and high-risk IPSS groups. 1

Disease Classification and Risk Assessment

Before initiating Inqovi, proper risk stratification is essential:

• Use IPSS-R for most accurate risk stratification (preferred over original IPSS) 2
• Risk categories that benefit from Inqovi:
  • IPSS Intermediate-1 and above 2
  • IPSS-R Intermediate (score >3.5), High, and Very High 2

Treatment Algorithm

For Higher-Risk MDS (IPSS Int-2, High; IPSS-R High, Very High):

1. First-line options:

   • Allogeneic stem cell transplant (if eligible) 2
   • Hypomethylating agents (HMAs) including:
     • Azacitidine (preferred if not transplant eligible) 2
     • Decitabine 2
     • Inqovi (oral decitabine/cedazuridine) 2, 1

2. Treatment considerations:

   • Inqovi can be used as a direct substitute for intravenous decitabine 2
   • Continue treatment for at least 4-6 cycles to properly assess response 2
   • For transplant candidates, Inqovi may be used as a bridge to reduce marrow blast count 2

For Intermediate-Risk MDS:

• IPSS-R Intermediate with score ≤3.5: Manage as lower-risk MDS
• IPSS-R Intermediate with score >3.5: Manage as higher-risk MDS 2
• Inqovi is appropriate for IPSS Intermediate-1 and above 2

Mechanism and Benefits

Inqovi combines:

• Decitabine: A DNA methyltransferase inhibitor that promotes DNA hypomethylation
• Cedazuridine: A cytidine deaminase inhibitor that prevents degradation of decitabine in the GI tract and liver, enabling oral administration 1, 3

Key advantages:

• Oral formulation improves patient convenience compared to parenteral administration
• Similar efficacy to IV decitabine with comparable safety profile 3
• Potentially improved compliance due to oral administration

Dosing and Administration

• Standard dosing of Inqovi (decitabine 35mg/cedazuridine 100mg) 1
• Typical administration is on days 1-5 of 28-day cycles 1
• Alternative schedules may be considered based on patient tolerance

Response Assessment

• Continue for at least 4-6 cycles to properly assess response 2
• Responses may include:
  • Complete remission (CR)
  • Partial remission (PR)
  • Hematologic improvement (HI) 2
• Achievement of HI should be considered indicative of response as it has been associated with prolongation of survival 2

Monitoring and Toxicity Management

• Regular monitoring of blood counts is essential
• Primary toxicities include myelosuppression 4
• Grade 3/4 neutropenia and thrombocytopenia are common adverse effects 5
• Dose modifications may be required based on cytopenias

Special Considerations

• Inqovi may also be considered in the post-allogeneic transplant setting as maintenance therapy to prevent relapse in high-risk patients 4
• For patients with IDH1/2 mutations, combination approaches with targeted inhibitors may be considered 2

Pitfalls and Caveats

• Response to hypomethylating agents including Inqovi may take several cycles - avoid premature discontinuation
• Lower doses of decitabine (15 mg/m²/day) may be associated with lower hematologic toxicity while maintaining efficacy in some patients 5
• Failure to achieve response after adequate trial (4-6 cycles) should prompt consideration of alternative therapies or clinical trials 2
• Patients should be monitored for infections due to treatment-related myelosuppression

Inqovi represents an important advancement in MDS treatment by providing an effective oral alternative to parenteral decitabine, potentially improving quality of life while maintaining efficacy in this challenging patient population.