What disease is treated with Daratumumab (daratumumab) and Cybor D (cyclophosphamide, bortezomib, and dexamethasone)?

Daratumumab and CyBorD in the Treatment of Multiple Myeloma

Daratumumab in combination with CyBorD (cyclophosphamide, bortezomib, and dexamethasone) is primarily used in the treatment of multiple myeloma, both in newly diagnosed and relapsed settings. 1

Treatment Indications and Efficacy

• Daratumumab combined with CyBorD has demonstrated significant efficacy in newly diagnosed multiple myeloma (NDMM) patients, with very good partial response (VGPR) or better seen in 44.2% and overall response rate (ORR) of 79.1% after 4 cycles of induction therapy 1
• The 12-month progression-free survival (PFS) rate with this regimen was 87%, and the 12-month overall survival (OS) rate was 98.8% in newly diagnosed patients 1, 2
• This combination has also shown efficacy in relapsed multiple myeloma (RMM) patients 1, 3
• The NCCN Panel has included daratumumab/bortezomib/cyclophosphamide/dexamethasone as a treatment option for multiple myeloma patients 1

Mechanism and Treatment Protocol

• Daratumumab is a CD38-targeted monoclonal antibody that works through multiple mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and direct apoptosis induction 4
• CyBorD consists of:
  • Cyclophosphamide (typically 300 mg/m² orally weekly) 5
  • Bortezomib (1.3-1.5 mg/m² intravenously or subcutaneously) 2, 5
  • Dexamethasone (40 mg weekly) 2, 5
• When combined with daratumumab, the standard dosing is daratumumab 16 mg/kg administered intravenously according to the approved schedule 2

Comparative Efficacy and Treatment Selection

• In transplant-eligible patients, daratumumab-containing regimens have shown deeper response rates compared to non-daratumumab regimens 1
• The CASSIOPEIA trial demonstrated that adding daratumumab to bortezomib/thalidomide/dexamethasone resulted in deeper response rates (CR or better of 39% vs 26%) 1
• For relapsed multiple myeloma, treatment selection depends on previous therapies:
  • For patients refractory to lenalidomide, daratumumab/bortezomib/dexamethasone (DVd) is recommended 1, 6
  • For patients refractory to bortezomib, daratumumab/lenalidomide/dexamethasone (DRd) is recommended 1, 6

Safety Profile and Adverse Events

• Common adverse events with daratumumab-based regimens include:
  • Infusion-related reactions (primarily during first infusion) 6, 2
  • Neutropenia and other hematologic toxicities 6
  • Fatigue and upper respiratory tract infections 6, 2
• In the LYRA study of D-VCd, fatigue (59%) and neutropenia (13%) were the most frequent treatment-emergent adverse events 2
• Infusion reactions occurred in 54% of patients, primarily during the first dose, and were generally mild (2% grade 3) 2

Special Considerations

• For patients with secondary plasma cell leukemia or extensive extramedullary disease, more intensive regimens like VDT-PACE (bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide) may be considered 1
• Daratumumab can interfere with blood compatibility testing and response assessment, requiring special attention during therapy 4
• The CyBorD regimen alone (without daratumumab) has shown high response rates in newly diagnosed MM with 88% overall response rate and 61% very good partial response or better 5

Emerging Applications

• Daratumumab plus CyBorD is also being evaluated in light chain (AL) amyloidosis with promising results in the ANDROMEDA study, showing 96% overall hematologic response rate and 54% complete hematologic response 7

In conclusion, daratumumab in combination with CyBorD represents an effective treatment option for multiple myeloma patients, with robust efficacy data in both newly diagnosed and relapsed settings, and a manageable safety profile.