A phase III study published in Annals of Hematology assessed the effect of adding continuous low-dose cyclophosphamide to the backbone regimen of bortezomib and low-dose dexamethasone, in patients with primary Refractory or Relapsed Multiple Myeloma (RRMM).
The open-label, randomized and controlled study was terminated early however, due to insufficient sample size. Descriptive results were published by Martin Kropff, Department of Haematology at Medizinische Klinik III, Osnabrück, Germany, and colleagues.
- Patients (pts) n = 90
- Median follow-up = 24 months
- Pts randomized 1:1 to receive eight 3-week cycles of bortezomib 1.3 mg/m2 and dexamethasone 20 mg (VD; n = 43) alone, or in combination with cyclophosphamide at 50 mg (VCD; n = 47)
- Median Time to Progression (TTP): VD vs VCD = 6 vs 9.9 months (P = 0.192)
- Disease Progression: VD vs VCD = 65% vs 72% (HR = 0.71, 95% CI; 0.43–1.19, P = 0.196)
- Overall Response Rate (ORR): VD vs VCD = 32 pts (74%) vs 33 pts (70%)
- Median OS: VD vs VCD = not determined vs 41 months
- Grade ≥3 peripheral neuropathy: VD vs VCD = 4% vs 15%
- Infection rate: VD vs VCD = 52% vs 64%
- Most common Adverse Events (AEs): thrombocytopenia (38%), peripheral neuropathy (35%), fatigue (34%), diarrhea (30%), constipation (25%) and anemia (19%)
- Death: VD vs VCD = 13 pts (30%) vs 18 pts (38%) (HR = 0.85, 95% CI = 0.41–1.73, P = 0.645)
The study results for median TTP, ORR and disease progression did not indicate an additional benefit for the use of VCD compared with VD, for the treatment of primary RRMM patients. However, since the proposed sample size was not reached and the study was terminated early, further trials may be required to fully assess the clinical benefit of VCD. The safety profiles of both therapies were relatively similar with VCD showing slightly higher grade ≥3 peripheral neuropathy. The authors commented that the lack of benefit may be due to the use of a low-dose of cyclophosphamide and therefore investigating higher dosing schedules in a VCD combo may be of interest.