Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial

Hematology. 2022 Dec;27(1):239-248. doi: 10.1080/16078454.2022.2032915.

Abstract

Objectives: We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542).

Methods: From 2013 to 2016, 42 patients with a median age of 58 (range 42-65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated.

Results: Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%-97.5%) and 62.6% (95% CI: 45.8%-75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation.

Conclusion: VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan.

Keywords: Japan; Multiple myeloma; autologous stem cell transplantation; bortezomib; consolidation therapy; cyclophosphamide; induction therapy; maintenance therapy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Autografts
  • Bortezomib / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / administration & dosage
  • Disease-Free Survival
  • Female
  • Humans
  • Induction Chemotherapy*
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / therapy
  • Prospective Studies
  • Stem Cell Transplantation*
  • Survival Rate

Substances

  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide