A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients
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Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM.
Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1–3 intravenously.
After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3–4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS.
The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients.
Trial registration ClinicalTrials.gov: NCT02086942.
KeywordsMultiple myeloma Bortezomib Subcutaneous injection Different doses Efficacy
The authors would like to acknowledge colleagues at Jinling Hospitals for the detailed scientific discussion. This work was supported by grants from the National Natural Science Foundation of China for Young Scholars (Grant No. 81800126) and the Six Talent Peak Project in Jiangsu Province (Grant No. 2015-WSN-011).
FL designed and conducted the experiments and wrote the manuscript. FL, F-SY, X-JZ, W-YG, X-HW, BC, D-PH, J-HD, T-QW, YZ, QZ, Y-MT, PS, X-GZ, Z-MA, XG, X-LW, LZ and X-BX carried out the collection of samples and clinical data. FL conducted the analysis of the clinical data. Y-PZ contributed to the experimental design, the review and revision of the manuscript, and the final approval of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that no conflicts of interest exist.
All patients provided written informed consent for the use of their samples and data, and the study was approved by the Ethics Committee of Jinling Hospital, Nanjing, China.
- Bensinger WI, Jagannath S, Vescio R et al (2010) Phase 2 study of two sequential three-drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma. Br J Haematol 148:562–568CrossRefGoogle Scholar
- Cavo M, Tacchetti P, Patriarca F et al (2010) Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 376:2075–2085CrossRefGoogle Scholar
- Harousseau JL, Attal M, Avet-Loiseau H et al (2010) Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 28:4621–4629CrossRefGoogle Scholar
- Lightcap ES, McCormack TA, Pien CS et al (2000) Proteasome inhibition measurements: clinical application. Clin Chem 46:673–683Google Scholar
- Mateos MV, Oriol A, Martinez-Lopez J et al (2010) Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 11:934–941CrossRefGoogle Scholar
- Tanake K, Toyota S, Akiyama M et al (2019) Efficacy and safety of a weekly cyclophosphamide–bortezomib–dexamethasone regimen as induction therapy prior to autologous stem cell transplantation in japanese patients with newly diagnosed multiple myeloma: a phase 2 multicenter trial. Acta Haematol 141:111–118CrossRefGoogle Scholar
- Tricot G, Jagannath S, Vesole D et al (1995) Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood 85:588–596Google Scholar