What are some bortezomib (Velcade) based regimens?

Bortezomib-Based Regimens for Multiple Myeloma

Bortezomib-based triplet regimens are highly effective treatment options for multiple myeloma, with VTD (bortezomib, thalidomide, dexamethasone), VRD (bortezomib, lenalidomide, dexamethasone), VCD (bortezomib, cyclophosphamide, dexamethasone), and PAD (bortezomib, adriamycin, dexamethasone) being the most commonly recommended combinations. 1

First-Line Bortezomib-Based Regimens

Transplant-Eligible Patients

• VTD (Bortezomib, Thalidomide, Dexamethasone)

  • Highest level of evidence (1A recommendation) 1
  • Overall response rate (ORR): 88-94%
  • Very good partial response (VGPR) or better: 61-62%
  • Complete response (CR): 32-39%
  • Notable for superior response rates compared to VCD 1

• VRD (Bortezomib, Lenalidomide, Dexamethasone)

  • Strong evidence (1B recommendation) 1
  • Better toxicity profile than thalidomide-containing regimens
  • Advantage of oral administration for lenalidomide component

• VCD (Bortezomib, Cyclophosphamide, Dexamethasone)

  • Strong evidence (1B recommendation) 1
  • ORR: 77%
  • Particularly useful in patients with renal impairment 1, 2
  • Lower peripheral neuropathy rates compared to IMiD combinations 3

• PAD (Bortezomib, Adriamycin, Dexamethasone)

  • Strong evidence (1A recommendation) 1
  • ORR: 65%
  • VGPR or better: 16%
  • CR: 7%

Transplant-Ineligible Patients

• VMP (Bortezomib, Melphalan, Prednisone)
• VRd (Bortezomib, Lenalidomide, low-dose Dexamethasone)
• VCD (Bortezomib, Cyclophosphamide, Dexamethasone)

Relapsed/Refractory Setting

• DVd (Daratumumab, Bortezomib, Dexamethasone) - preferred option for first relapse 1

• VCD (Bortezomib, Cyclophosphamide, Dexamethasone)

  • Well-tolerated option with lower neurotoxicity 4, 3
  • Comparable efficacy to lenalidomide-based regimens at first relapse 4

• VTD-PACE (Bortezomib, Thalidomide, Dexamethasone, Cisplatin, Adriamycin, Cyclophosphamide, Etoposide)

  • Intensive regimen for aggressive disease 1

• VPd (Bortezomib, Pomalidomide, Dexamethasone)

  • Option for lenalidomide-refractory patients 1

Special Clinical Scenarios

Renal Impairment

• VCD is preferred due to:
  • No dose adjustment needed for bortezomib 2
  • Favorable renal safety profile 1, 2
  • Demonstrated efficacy in patients with renal failure 1

High-Risk Cytogenetics

• Bortezomib-based triplets are particularly valuable for:
  • Patients with del(17p), t(4;14), or 1q21 abnormalities 1
  • Chromosome 13 deletion 5

Plasma Cell Leukemia

• Bortezomib-based intensive regimens such as:
  • VTD-PACE or HyperCVAD-VD 1
  • Aim for rapid cytoreduction to minimize early mortality

Administration and Toxicity Management

• Subcutaneous administration of bortezomib is preferred over IV to reduce peripheral neuropathy 2
• Once-weekly dosing (rather than twice-weekly) can reduce neuropathy while maintaining efficacy 2
• Herpes zoster prophylaxis is recommended during bortezomib therapy 1, 2
• Dose modifications at first sign of neuropathy are essential 2

Comparative Efficacy

• In head-to-head comparisons, VCD and RCD (lenalidomide-based) regimens show similar efficacy at first relapse:

  • Similar VGPR rates (15% vs 18%)
  • Similar PFS (16.3 vs 18.6 months) 4
  • However, VCD shows lower rates of peripheral neuropathy (8% vs 47.3%) compared to IMiD combinations 3

• Higher-dose bortezomib (1.6 mg/m²) may achieve faster and deeper responses than standard dose (1.3 mg/m²), particularly in younger patients (<65 years) and those with high-risk disease, but with increased GI toxicity 6

Pitfalls and Caveats

• Peripheral neuropathy is more common with bortezomib plus IMiDs (thalidomide/lenalidomide) than with bortezomib plus cyclophosphamide 3
• Thromboprophylaxis is essential when combining bortezomib with IMiDs 2
• Avoid stem cell toxins (e.g., melphalan) in transplant-eligible patients 1
• Renal function may improve more rapidly with VRD than VCD in patients with renal impairment 7
• Maintenance therapy after induction significantly improves outcomes regardless of induction regimen choice 7

Bortezomib-based regimens remain cornerstone therapies in multiple myeloma treatment, with triplet combinations demonstrating superior efficacy compared to doublets, and selection should be based on disease characteristics, patient comorbidities, and prior treatment exposure.