| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Bortezomib | 1.3 mg/m2 SC or IV* | Given as a single SC[4] injection or as a rapid IV bolus over three to five seconds. | Days 1, 8, and 15[3,5] |
| Lenalidomide¶ | 25 mgΔ by mouth | Administer with water. Swallow capsule whole; do not break, open, or chew. | Daily, on days 1 through 14 |
| Dexamethasone | 40 mgΔ by mouth | Take with food (after meals or with food or milk) in the morning. | Days 1, 8, and 15[3] |
| Pretreatment considerations: |
| Emesis risk | - MINIMAL TO LOW.
- Refer to UpToDate topic on "Prevention and treatment of chemotherapy-induced nausea and vomiting in adults".
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| Prophylaxis for infusion reactions | - Routine premedication is not indicated. If a hypersensitivity reaction (not including local reactions) occurs with bortezomib or lenalidomide, then neither drug should be readministered.
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| Antithrombotic prophylaxis | - Routine antithrombotic prophylaxis is warranted. Thromboembolism was reported in 2 to 6% of patients in clinical trials receiving VRd despite antithrombotic prophylaxis.[1,2] The risk of thromboembolism was over 10% with another lenalidomide and high-dose dexamethasone (RD) regimen.[6]
- Refer to UpToDate topic on "Thrombotic complications following treatment of multiple myeloma with immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide)".
|
| Infection prophylaxis | - Bortezomib therapy may be associated with an increased risk of herpes zoster and infections not related to neutropenia. Antiviral prophylaxis (eg, acyclovir 400 mg orally twice a day) should be administered to all patients receiving VRd. Some clinicians also administer prophylactic trimethoprim-sulfamethoxazole (eg, one double-strength tablet once daily on Mondays, Wednesdays, and Fridays) during treatment.[1,2] Primary prophylaxis with G-CSF is not indicated.
|
| Vesicant/irritant properties | - Bortezomib is an irritant.
- Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-antineoplastic vesicants".
|
| Dose adjustment for baseline liver or renal dysfunction | - Bortezomib: No dosage adjustment for bortezomib secondary to renal insufficiency is necessary.[7] For patients undergoing hemodialysis, bortezomib should be administered after dialysis. Patients with moderate or severe hepatic impairment (serum bilirubin level >1.5 times the ULN) should be started on bortezomib at a reduced dose of 0.7 mg/m2 per injection during the first cycle, with further dose modifications based upon patient tolerance. Refer to UpToDate topic on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents".
- Lenalidomide: Patients with renal insufficiency experience more neutropenia with lenalidomide.[8] Dose adjustment is recommended for patients with CrCl <60 mL/min.[9] At this time, studies have not been conducted in patients with hepatic impairment.
- Refer to UpToDate topics on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Conventional cytotoxic agents" and "Chemotherapy hepatotoxicity and dose modification in patients with liver disease: Molecularly targeted agents" and "Chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency: Conventional cytotoxic agents".
|
| Monitoring parameters: |
- Assess CBC with differential, electrolytes, renal function, and liver function prior to starting each cycle. A CBC should also be performed prior to the day 8 and 15 doses of bortezomib during induction therapy.
|
- Weekly assessment for peripheral neuropathy and/or neuropathic pain.
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- Monitor for hypotension during bortezomib therapy; adjustment of antihypertensives and/or administration of IV hydration may be needed.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - A cycle of VRd should not be started unless the ANC is ≥1000/microL and the platelet count is ≥70,000/microL.[1,2,7] If platelets are <50,000/microL or the ANC is <1000/microL on day 15, hold day 15 bortezomib dose. If several doses are held, reduce bortezomib dose by one level (from 1.5 mg/m2 to 1.3 mg/m2 or from 1.3 mg/m2 to 1 mg/m2 or from 1 mg/m2 to 0.7 mg/m2) and decrease the daily dose of lenalidomide by 5 mg. Growth factor support can be given on day 8 of the second and subsequent cycles for ANC <500/m2 lasting >7 days or for an episode of febrile neutropenia.[1,2]
|
| Neuropathy | - Bortezomib dose should be reduced in patients who develop symptomatic peripheral neuropathy.[7] Rates of neuropathy appear to be lower with subcutaneous administration of bortezomib.[4]
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| Thrombotic microangiopathy | - Rarely, bortezomib has been associated with TMA, which can present with Coombs-negative hemolysis, thrombocytopenia, renal failure, and/or neurologic findings.[7] If TMA is suspected, stop bortezomib and evaluate.
- Refer to UpToDate topic on "Drug-induced thrombotic microangiopathy".
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| Other nonhematologic toxicity | - For grade 3 or 4 nonhematologic toxicity other than neuropathy, hold lenalidomide and bortezomib. Once symptoms have resolved to grade 1 or baseline, reinitiate therapy with lower doses. Reduce dexamethasone dose for grade 2 muscle weakness, grade 3 gastrointestinal tract toxicity, hyperglycemia, confusion, or mood alterations.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
