Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study
- Study type
- Clinical trial
- Study name
- MMY-3021
- Phase
- Phase 3
- Design
- Randomised, open-label (patients and physicians not blinded), non-inferiority, multicentre trial (53 centres in 10 countries in Europe, Asia and South America)
- Sample size
- 222 patients
- Source
- The Lancet Oncology · 2011
- Trial registration
- NCT00722566
In plain words
Bortezomib is an important drug for treating multiple myeloma and is usually given into a vein. In this study, injecting the same drug under the skin was compared with giving it into a vein. The response to treatment was the same with both methods (42%), but nerve damage in the hands and feet (neuropathy) was seen less often with the under-the-skin injection. The under-the-skin injection was also well tolerated at the injection site.
Key results
Treatment arms and regimens
Bortezomib 1.3 mg/m² on days 1, 4, 8 and 11 of each 21-day cycle, by subcutaneous injection, for up to eight cycles (148 patients randomised; 145 in the response-evaluable population).
Bortezomib 1.3 mg/m² on days 1, 4, 8 and 11 of each 21-day cycle, by IV infusion, for up to eight cycles (74 patients randomised; 73 in the response-evaluable population).
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged 18 years and older with multiple myeloma relapsed after one to three prior lines of therapy. The response-evaluable population comprised patients with measurable, secretory multiple myeloma who had received at least one dose of study drug.
Endpoints
Primary objective: to show non-inferiority of subcutaneous versus IV bortezomib in overall response rate (ORR) after four cycles in the response-evaluable population. Non-inferiority was defined as retaining 60% of the effect of IV treatment. Other endpoints included time to progression, 1-year overall survival and safety.
Safety and side effects
Grade 3 or higher adverse events were reported in 84 patients (57%) in the subcutaneous group versus 52 patients (70%) in the IV group. The most common were thrombocytopenia (13% versus 19%), neutropenia (18% versus 18%) and anaemia (12% versus 8%). Peripheral neuropathy at all grade levels (any grade, grade 2 or higher and grade 3 or higher) was significantly less common with subcutaneous than with IV administration. Subcutaneous administration was well tolerated locally.
Clinical significance and place in guidelines
This study showed that subcutaneous bortezomib, at the same dose and schedule, is non-inferior in efficacy to IV administration and causes less peripheral neuropathy; subcutaneous administration can therefore be an appropriate alternative to the IV route. Current regulatory approvals and guideline recommendations should be checked separately, as the abstract does not address them.
Limitations
The study was open-label, so patients and physicians knew the treatment assigned. The primary endpoint was response rate after four cycles and follow-up was relatively short (median about 12 months); the study was continuing for long-term follow-up. The study was conducted in relapsed patients with one to three prior lines of therapy.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.