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. 2019;141(2):111-118. doi: 10.1159/000495338. Epub 2019 Feb 6.

Abstract

We assessed the efficacy and safety of weekly cyclophosphamide-bortezomib-dexamethasone (CBD) induction prior to autologous stem cell transplantation (ASCT) in newly diagnosed Japanese patients with multiple myeloma (MM). This regimen consisted of four 28-day cycles of once-weekly oral cyclophosphamide (300 mg/m2), subcutaneous bortezomib (1.3 mg/m2), and oral dexamethasone (40 mg). Responding patients underwent stem cell collection followed by ASCT. The primary endpoint was the postinduction rate of achieving a near complete response (nCR) or better. Among the 38 enrolled patients, a complete response (CR), an nCR, a very good partial response (VGPR), and a partial response (PR) were achieved in 10.5, 2.6, 23.7, and 36.8% of cases, respectively. A grade 4 hematological adverse event (AE) was observed in 1 patient. Grade 3-4 infection, including febrile neutropenia, was observed in 4 patients (10.5%). Although 2 patients dropped out due to AE, 94.7% of the patients completed the induction phase. However, because of a poor response to induction chemotherapy (<PR in 6 patients), poor stem cell mobilization (4 patients), and a protocol violation (1 patient), only 24 patients (63.2%) proceeded to ASCT. The 2-year progression-free and overall survivals were 55.3 and 82.7%, respectively. We thus believe that the therapeutic power of weekly CBD is not strong enough as a 3-drug induction regimen despite its feasibility for most Japanese patients.

Keywords: Autologous stem cell transplantation; Bortezomib; Cyclophosphamide; Dexamethasone; Induction; Multiple myeloma; Weekly cyclophosphamide-bortezomib-dexamethasone.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / administration & dosage*
  • Bortezomib / adverse effects
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Dexamethasone / administration & dosage*
  • Dexamethasone / adverse effects
  • Drug Administration Schedule
  • Female
  • Hematologic Diseases / etiology
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Survival Analysis
  • Transplantation, Autologous
  • Treatment Outcome
  • Young Adult

Substances

  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide