The response to second-line induction with bortezomib and dexamethasone is predictive of long-term outcomes prior to high-dose chemotherapy with autologous stem cell transplantation for multiple myeloma

Intern Med. 2013;52(9):961-8. doi: 10.2169/internalmedicine.52.9385. Epub 2012 Mar 1.

Abstract

Objective: We retrospectively investigated the efficacy and predictive factors for the treatment outcomes of bortezomib plus dexamethasone (BD) as second-line induction therapy prior to high-dose chemotherapy supported by autologous stem cell transplantation (HDT/ASCT) in multiple myeloma (MM) patients.

Methods: Sixty-six transplant eligible MM patients treated by the Kyoto Clinical Hematology Study Group between 2006 and 2011 were investigated. Conventional induction chemotherapy, including vincristine, doxorubicin and dexamethasone (VAD) and high-dose dexamethasone (HDD), was used as first-line induction therapy in all patients, seven (10.6%) of whom attained a very good partial response (VGPR). Of the 59 patients who did not attain VGPR with VAD or HDD, 33 were given BD as second-line induction therapy prior to HDT/ASCT.

Results: Patients not treated with BD induction showed an overall response rate (ORR, i.e., better than partial response) of 85.3% after induction therapy, while the ORR of patients treated with BD induction improved from 42.4% after conventional induction therapy to 84.8% after BD. The overall survival (OS) and progression-free survival (PFS) of patients not treated with BD induction were not significantly influenced by the response to induction therapy. Among the patients treated with BD, failure in attaining VGPR prior to ASCT was associated with a significantly shorter PFS and it also tended to show a shorter OS, while the disease stage and achievement of a complete response after HDT/ASCT had no impact on OS or PFS.

Conclusion: The achievement of at least VGPR with second-line BD induction therapy is a prerequisite for attaining longer OS and PFS after HDT/ASCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Boronic Acids / administration & dosage
  • Boronic Acids / adverse effects
  • Bortezomib
  • Chromosome Aberrations
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Drug Administration Schedule
  • Female
  • Forecasting
  • Hematologic Diseases / chemically induced
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / surgery
  • Peripheral Blood Stem Cell Transplantation*
  • Peripheral Nervous System Diseases / chemically induced
  • Prednisone / administration & dosage
  • Pyrazines / administration & dosage
  • Pyrazines / adverse effects
  • Remission Induction
  • Retrospective Studies
  • Transplantation, Autologous
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Boronic Acids
  • Pyrazines
  • Vincristine
  • Bortezomib
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Melphalan
  • Prednisone

Supplementary concepts

  • CHOP protocol
  • CVAD protocol