CyBorD + Daratumumab and Hyaluronidase for Multiple Myeloma
The recommended regimen is daratumumab/bortezomib/cyclophosphamide/dexamethasone (D-CyBorD), with subcutaneous daratumumab and hyaluronidase-fihj as the preferred formulation, administered as induction therapy followed by daratumumab maintenance. 1
Treatment Regimen Structure
Induction Phase (4-8 cycles)
- Bortezomib: 1.5 mg/m² subcutaneously weekly on days 1,8,15, and 22 of each 28-day cycle 2
- Cyclophosphamide: 300 mg/m² orally weekly on days 1,8,15, and 22 2
- Dexamethasone: 40 mg orally weekly on the day of bortezomib administration 2
- Daratumumab and hyaluronidase-fihj: Subcutaneous injection per approved dosing schedule 1
The subcutaneous formulation of daratumumab with hyaluronidase-fihj is preferred over intravenous daratumumab because it provides similar efficacy, safety profile, and fewer infusion-related reactions 1. However, avoid subcutaneous administration in patients with significant thrombocytopenia 1.
Maintenance Phase
Continue daratumumab monthly for up to 12 doses after completing induction therapy 2.
Clinical Efficacy Data
In newly diagnosed multiple myeloma patients, this regimen demonstrates:
- Very good partial response (VGPR) or better: 44.2% after 4 cycles, improving to 56% at end of induction 2
- Overall response rate (ORR): 79.1% after 4 cycles, improving to 81% at end of induction 2
- 12-month progression-free survival rate: 87% 2
- 12-month overall survival rate: 98.8% 2
In relapsed multiple myeloma patients (small cohort, n=14):
Administration Considerations
Bortezomib Route
Use subcutaneous bortezomib exclusively rather than intravenous administration, as it provides noninferior efficacy with significantly reduced peripheral neuropathy rates 1.
Daratumumab First Dose Management
The first daratumumab infusion can be split across two days in Cycle 1 to improve tolerability 2. Median infusion times are 4.5 hours for the first dose and 3.8 hours for the second dose 2.
Infusion Reactions
Infusion-related reactions occur in approximately 54% of patients, primarily during the first dose, with most being mild (only 2% grade 3) 2. The subcutaneous formulation reduces these reactions compared to intravenous administration 1.
Toxicity Profile and Management
Most Common Adverse Events
- Fatigue: 59% of patients 2
- Neutropenia: 13% grade 3/4 2
- Peripheral neuropathy: Minimized by weekly subcutaneous bortezomib dosing 2
Required Prophylaxis
- Herpes zoster prophylaxis is mandatory for all patients receiving proteasome inhibitors (bortezomib) or daratumumab 1
- Thromboprophylaxis: Full-dose aspirin recommended; therapeutic anticoagulation for high-risk patients 1
Monitoring Considerations
Daratumumab may interfere with serological testing and cause false-positive indirect Coombs test 1.
Clinical Context and Patient Selection
Newly Diagnosed Multiple Myeloma
This regimen is included by NCCN as a treatment option for both transplant-eligible and transplant-ineligible patients 1. It is particularly valuable as:
- Preferred initial treatment in acute renal insufficiency, with consideration to switch to bortezomib/lenalidomide/dexamethasone after renal function improves 1
- Bridge therapy for patients initially ineligible for transplant who may become eligible after achieving deep responses 2
Relapsed/Refractory Multiple Myeloma
D-CyBorD is listed as an "other recommended regimen" for relapsed/refractory disease after 1-3 prior therapies 1.
Stem Cell Collection
All patients in clinical trials who underwent stem cell harvest had successful collection, indicating this regimen does not impair stem cell mobilization 3, 2.
Treatment Duration
Administer 4-8 cycles of induction therapy based on response and transplant eligibility, followed by up to 12 monthly maintenance doses of daratumumab 2.