Does Bortezomib (Velcade) need to be administered before Daratumumab (Darzalex Faspro)?

Administration Sequence of Bortezomib and Daratumumab

No, bortezomib (Velcade) does not need to be administered before daratumumab (Darzalex Faspro) - these agents can be given in any order on the same day, or the regimen can be structured with daratumumab given on different days than bortezomib depending on the treatment schedule being used.

Evidence from Combination Regimens

The combination of daratumumab with bortezomib and dexamethasone (DVd) has been extensively studied without any requirement for specific sequencing:

• In the CASTOR trial, daratumumab was administered on days 1,8, and 15 of 21-day cycles (cycles 1-3), then every 3 weeks (cycles 4-8), then every 4 weeks, while bortezomib was given on days 1,4,8, and 11 1
• The DVd regimen showed impressive efficacy with a hazard ratio of 0.39 for progression-free survival compared to bortezomib-dexamethasone alone, demonstrating that this scheduling (with overlapping but non-sequential administration) is both safe and highly effective 1

Practical Administration Considerations

When both drugs are scheduled on the same day:

• Either agent can be administered first - there is no pharmacologic interaction requiring specific sequencing 1
• Daratumumab infusion time considerations: The first infusion takes approximately 6.5 hours, while subsequent infusions take 3.5 hours with required premedication 1
• Subcutaneous daratumumab (Darzalex Faspro) is preferred as it reduces administration time and infusion-related reactions while maintaining equivalent efficacy 2
• Bortezomib should be given subcutaneously rather than intravenously, as this significantly reduces peripheral neuropathy rates while maintaining noninferior efficacy 3, 2

Treatment Schedule Flexibility

The regimens demonstrate considerable flexibility in scheduling:

• D-CyBorD regimen (daratumumab/bortezomib/cyclophosphamide/dexamethasone) is recommended by NCCN with subcutaneous daratumumab as the preferred formulation, followed by daratumumab maintenance 2
• In transplant-eligible patients, the GRIFFIN study used daratumumab weekly during cycles 1-4, then on day 1 of cycles 5-6, combined with bortezomib on days 1,4,8, and 11 of 21-day cycles - showing that staggered scheduling is effective 4

Key Safety Measures (Not Sequencing-Related)

Mandatory prophylaxis regardless of administration order:

• Herpes zoster prophylaxis is required for all patients receiving proteasome inhibitors or daratumumab 3, 2
• Thromboprophylaxis with full-dose aspirin is recommended, with therapeutic anticoagulation for high-risk patients 2
• Weekly bortezomib dosing reduces Grade 3/4 neuropathy to 6-7% compared to twice-weekly schedules 3

Clinical Context

The lack of required sequencing is supported by:

• Multiple phase 3 trials showing efficacy without mandated drug order 1
• DVd is a preferred option for lenalidomide-refractory patients at first relapse, with no sequencing requirements mentioned in treatment algorithms 1
• The combination is well-tolerated with predictable adverse events that are manageable through monitoring and supportive care, not through administration sequencing 3