Bortezomib-based regimens
Bortezomib was the first proteasome inhibitor to be used in the treatment of myeloma. Its mechanism of action has proven to be highly effective against myeloma and its introduction has been one of the most important breakthroughs in the history of the disease.
Bortezomib is approved as a first-line treatment in combination with an alkylating chemotherapy agent and a steroid for patients who are not eligible for HDT-SCT, who are intolerant to or have a contraindication for thalidomide and/or who are considered high risk. These patients include those who:
- Have renal impairment
- Have other co-morbidities that potentially increase toxicity
- Have thrombophilia or a history of severe thrombosis
- Are hypersensitive or allergic to thalidomide
- Are pregnant, or are of child-bearing age unable to follow or comply with the required contraceptive measures
The two most common treatment combinations in these patients are:
- Bortezomib, melphalan, prednisolone (VMP)
- Bortezomib, cyclophosphamide, dexamethasone (VCD)
Efficacy
Evidence for the efficacy of bortezomib as a first-line treatment for older and/or less-fit patients came from the pivotal VISTA trial involving 682 patients with a median age of 71 years (30% > 75 years old). In combination with melphalan and prednisolone (VMP), the time to disease progression was 21 months compared to 15 months with melphalan and prednisolone (MP) only. A statistically significant survival benefit was also noted with VMP.
Administration
Bortezomib is usually administered subcutaneously but can also be given intravenously. Schedules vary depending on whether patients receive once or twice-weekly injections. The once-weekly schedule has been shown in several clinical trials to be equally effective but less toxic and is generally used in elderly patients. Some haematologists use once-weekly schedules for all patients including younger patients. A twice-weekly schedule might be used in patients when there is a need for a rapid response, such as patients with severe acute kidney injury.
Side effects
| Treatment | Potential side effects |
|---|---|
| Bortezomib | Nausea and vomiting, diarrhoea, constipation, thrombocytopenia, fatigue, peripheral neuropathy, dizziness, increased infections, especially shingles, muscle cramps and spasms |
| Melphalan/ Cyclophosphamide | Nausea and vomiting, diarrhoea, hair loss, weight loss, sore mouth, infections, fatigue, anaemia, skin rash, infertility |
| Prednisolone/ Dexamethasone | Stomach irritation, increased appetite, fluid retention, swelling in feet and hands, changes in blood sugar levels, infections, mood swings, insomnia, muscular problems, osteoporosis |
Patients on bortezomib regimens should be advised to avoid green tea and green tea supplements and large doses of Vitamin C, as well as reduce their alcohol intake. These can all affect how bortezomib works and exacerbate side effects. It is also not known if bortezomib is safe for unborn babies so it should not be taken during pregnancy or while breastfeeding.
Further reading
Facon et al. (2022) Treatment Regimens for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: A Systematic Literature Review and Network Meta-analysis. Adv Ther, 39:1976–1992
Mateos et al. (2020) The effects of different schedules of bortezomib, melphalan, and prednisone for patients with newly diagnosed multiple myeloma who are transplant ineligible: a matching-adjusted indirect comparison. Leuk Lymphoma, 61(3):680-690.
Facon et al. (2019) Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2;133(18):1953-1963.