The VRd REGIMEN
The “triplet” (3-drug) combination therapy of the proteasome inhibitor Velcade® (bortezomib) + the immunomodulatory agent Revlimid® (lenalidomide) + the steroid dexamethasone [VRd] is approved by the U.S. Food and Drug Administration (FDA) for patients with newly diagnosed multiple myeloma (NDMM) and continues to be used for relapsed or refractory disease. VRd is highly effective and well-tolerated. Each drug in the VRd regimen has a different way of attacking myeloma, and each enhances the activity of the other drugs in this combination.
Dose and schedule of VRd
Velcade is given at a dose of 1.3 mg/m2 (milligram per square meter of body mass) on days 1, 4, 8, and 11 of a 21-day Cycle. Velcade is usually given as a subcutaneous (SQ) injection but can also be given as an intravenous (IV) infusion. SQ Velcade was approved in 2012; injections of Velcade should be given using a sequential rotation of four sites: the left and right sides of the abdomen and the left and right thighs. There is no data from clinical trials to support SQ injections given in the arm.
Revlimid is a capsule taken orally with water at 25 mg per day on days 1–14 of a 21-day Cycle.
Dexamethasone is taken in pill form either with food or after a meal at 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of a 21-day Cycle.
Doses of each drug can be adjusted as determined by your doctor. Velcade can be given at a lower dose and/or weekly instead of twice-weekly. The “VRd-lite” regimen with weekly Velcade and a starting dose of 15 mg of Revlimid is used for patients who are older or frail. An alternative schedule of 28-day Cycles includes treatment given for 21 days, followed by 7 days off treatment.
Myeloma Foundation 4400 Coldwater Canyon Avenue #300 – Studio City, CA 91604 1.818.487.7455 TheIMF@myeloma.org myeloma.org
Special cautions with Velcade
ALL patients taking VRd should receive the following:
An anticoagulant (blood thinner) to prevent blood clots. The combination of Revlimid and dexamethasone is known to increase the risk for blood clots. Your doctor will prescribe a medication based on your medical history and the assessment of your risk for a blood clot.
Antiviral therapy to prevent herpes zoster (shingles), which is caused by the reactivation of the varicella-zoster virus (VZV), the same virus that causes varicella (chickenpox). When reactivated, the shingles infection frequently affects the nerves. All proteasome inhibitors, including Velcade, are known to increase the risk of shingles.
Possible side effects of VRd
The following are the most common side effects of VRd that were reported in more than 10% of clinical trial patients:
Neuropathy (23%), which is numbness, tingling, burning, or pain in the hands, feet, lower legs, or arms.
Low white blood cell counts, which can lead to infection: lymphocytes (23%), neutrophils (19%), leukocytes (14%)
Low thrombocyte count (18%), which can cause bleeding problems.
Fatigue (16%), which is a debilitating side effect commonly associated with cancer and with cancer therapy.
Low hemoglobin or anemia (13%), which may cause shortness of breath and/or feelings of exhaustion.
Promptly report to your doctor any unwanted or unexpected side effect or reaction that you experience.
VRd-based “quadruplet” combinations
In 2024, the FDA approved two new “quadruplet” (4-drug) therapies for NDMM of VRd plus a fourth drug: Darzalex Faspro® (daratumumab hyaluronidase-fihj) + VRd [DVRd] was approved in July; Sarclisa® (isatuximab-irfc) + VRd [Isa-VRd] was approved in September.
Use the QR code below or visit medications.myeloma.org for more information.
As always, the IMF urges you to discuss all medical issues with your doctor and to contact the IMF InfoLine with your myeloma-related questions and concerns at 1.818.487.7455 or infoline@myeloma.org .