Weekly Bortezomib Dosing in the VRD Regimen for Multiple Myeloma
Dosing Schedules
- Standard 3‑week VRD schedule: Bortezomib 1.3 mg/m² subcutaneously on days 1, 8, 15; lenalidomide 25 mg orally on days 1–14; dexamethasone 20 mg on the day of and the day after each bortezomib dose (or 40 mg on days 1, 8, 15, 22); cycles repeat every 21 days. [1] [2] [1] [3]
- Modified 4‑week “VRD‑lite” schedule: Bortezomib 1.3 mg/m² subcutaneously on days 1, 8, 15, 22; dexamethasone 20 mg on the day of and the day after each bortezomib dose; cycles repeat every 28 days. 1
Route of Administration
- Subcutaneous (SC) administration is strongly preferred over intravenous (IV) delivery because it provides equivalent anti‑myeloma efficacy while markedly reducing the risk of peripheral neuropathy. This recommendation is endorsed by contemporary guideline societies. 3
Combination with Anti‑CD38 Monoclonal Antibodies
- When VRD is combined with daratumumab or isatuximab (quadruplet regimens), the bortezomib schedule shifts to twice‑weekly dosing (days 1, 4, 8, 11) during cycles 1–8, after which therapy may transition to weekly dosing or discontinue bortezomib in favor of lenalidomide/dexamethasone maintenance. 4
- The twice‑weekly induction schedule in these quadruplet regimens is associated with a higher incidence of grade ≥ 2 peripheral neuropathy (≈ 27 % of patients). 4
Duration of Therapy
- VRD therapy should be continued until disease progression, with dose modifications as needed for toxicity. This applies to both transplant‑eligible and transplant‑ineligible patients. [4] [5]
- For transplant‑eligible patients, induction typically consists of 3–4 cycles before stem‑cell collection. 4
- For transplant‑ineligible patients, therapy is maintained until progression, with de‑escalation of agents when toxicity arises. [4] [5]
- Continuous VRD therapy (until progression) yields superior progression‑free and overall survival compared with a fixed‑duration approach. 5
Safety and Neuropathy
- Avoid IV bortezomib when SC formulation is available; IV administration increases the risk of peripheral neuropathy without added benefit. [3] [1] 2
Dose Adjustments in Renal Dysfunction
- Lenalidomide dose reductions based on creatinine clearance are recommended for patients with renal impairment; such reductions do not compromise anti‑myeloma efficacy. 5