What is the recommended treatment regimen for multiple myeloma using daratumumab (Darzalex), hyaluronidase?

Recommended Treatment Regimens for Multiple Myeloma Using Daratumumab, Hyaluronidase

Daratumumab with hyaluronidase (subcutaneous formulation) should be used in combination therapy as a preferred treatment option for relapsed multiple myeloma, with specific regimens selected based on prior treatment exposure. 1, 2

Subcutaneous Daratumumab Formulation

The subcutaneous formulation of daratumumab (DARA SC) offers significant advantages over the intravenous (IV) formulation:

• Administration time of only 3-5 minutes (versus several hours for IV) 3
• Lower rates of infusion-related reactions (≤10% versus approximately 50% for IV) 2, 4
• Non-inferior efficacy compared to IV daratumumab 2
• Standard fixed dose of 1800 mg co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) 5

First Relapse Treatment Regimens

For patients experiencing first relapse, the choice of daratumumab-based regimen depends on previous treatment exposure:

Lenalidomide-Refractory Disease:

• Daratumumab/Bortezomib/Dexamethasone (DVd) (Category 1, preferred) 1
  • Demonstrated 69% reduction in disease progression or death risk
  • Median PFS of 16.7 months vs 7.1 months with Vd alone
  • Greatest benefit in patients with one prior line of therapy (median PFS 27.0 vs 7.9 months)

Bortezomib-Refractory Disease:

• Daratumumab/Lenalidomide/Dexamethasone (DRd) (Category 1, preferred) 1
  • Significantly improved PFS (median not reached vs 18.4 months)
  • ORR of 92.9% vs 76.4% without daratumumab
  • 66% reduction in progression risk

Double-Refractory Disease (Lenalidomide and Bortezomib)

For patients refractory to both lenalidomide and bortezomib:

• Daratumumab/Pomalidomide/Dexamethasone (DPd) 1
  • Demonstrated improved PFS (12.4 vs 6.9 months) in the APOLLO trial
  • ORR of 77.7% in patients previously treated with lenalidomide

Dosing Schedule for Subcutaneous Daratumumab

The recommended dosing schedule for subcutaneous daratumumab (1800 mg) is 1, 5:

• Weekly for cycles 1-2 (weeks 1-8)
• Every 2 weeks for cycles 3-6 (weeks 9-24)
• Every 4 weeks thereafter until disease progression

Special Considerations

• Infusion-Related Reactions: Though less common with subcutaneous administration (≤10% vs 50% with IV), premedication is still recommended 2, 4
• Administration Time: Median administration time is only 5 minutes, significantly improving patient convenience 3
• Efficacy: Subcutaneous daratumumab achieves similar or greater serum concentrations compared to IV administration 5
• Monitoring: Regular assessment for common adverse events including neutropenia, thrombocytopenia, and upper respiratory infections is recommended 1

Treatment Selection Algorithm

1. Determine prior treatment exposure:

   • If lenalidomide-refractory → DVd
   • If bortezomib-refractory → DRd
   • If double-refractory → DPd

2. Assess patient characteristics:

   • For aggressive relapse or extramedullary disease → Consider more intensive regimens
   • For frail patients → Consider dose modifications while maintaining triplet therapy

3. Continue treatment until progression or unacceptable toxicity

Common Pitfalls to Avoid

• Underestimating the benefit of triplet regimens: Triplet regimens are superior to doublets and should be used whenever possible 1
• Overlooking the need for herpes zoster prophylaxis: Recommended for patients treated with proteasome inhibitors 1
• Failing to consider transplant: ASCT should be considered at relapse if not previously received or if PFS after first transplant was ≥18 months 1
• Not accounting for disease evolution: Regular restaging is important as the disease can evolve to secondary plasma cell leukemia or extramedullary myeloma 1

The subcutaneous formulation of daratumumab with hyaluronidase represents a significant advancement in multiple myeloma treatment, offering comparable efficacy to IV daratumumab with improved convenience and tolerability.