Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial.

Abstract

PURPOSE:

The combination of bortezomib-melphalan-prednisone (VMP) is a new standard of care for newly diagnosed multiple myeloma. This phase III study examined the efficacy of the four-drug combination of bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance with bortezomib-thalidomide (VMPT-VT) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation.

PATIENTS AND METHODS:

A total of 511 patients were randomly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance, or nine cycles of VMP at the same doses with no additional therapy. The primary end point was progression-free survival.

RESULTS:

The 3-year estimates of progression-free survival were 56% in patients receiving VMPT-VT and 41% in those receiving VMP (hazard ratio [HR], 0.67; 95% CI, 0.50 to 0.90; P = .008). At 3 years, the cumulative proportions of patients who did not go on to the next therapy were 72% with VMPT-VT and 60% with VMP (HR, 0.58; 95% CI, 0.50 to 0.90; P = .007). Complete response rates were 38% in the VMPT-VT group and 24% in the VMP group (P < .001). The 3-year overall survival was 89% with VMPT-VT and 87% with VMP (HR, 0.92; 95% CI, 0.53 to 1.60; P = .77). Grade 3 to 4 neutropenia (38% v 28%; P = .02), cardiologic events (10% v 5%; P = .04), and thromboembolic events (5% v 2%; P = .08) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group; treatment-related deaths were 4% with VMPT-VT and 3% with VMP.

CONCLUSION:

VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.

• Authors: Antonio Palumbo, Sara Bringhen, Davide Rossi, Maide Cavalli, Alessandra Larocca, Roberto Ria, Massimo Offidani, Francesca Patriarca, Chiara Nozzoli, Tommasina Guglielmelli, Giulia Benevolo, Vincenzo Callea, Luca Baldini, Fortunato Morabito, Mariella Grasso, Giovanna Leonardi, Manuela Rizzo, Antonietta Pia Falcone, Daniela Gottardi, Vittorio Montefusco, Pellegrino Musto, Maria Teresa Petrucci, Giovannino Ciccone, Mario Boccadoro
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 34 Pg. 5101-9 (Dec 01 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20940200 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Boronic Acids
• Pyrazines
• Thalidomide
• Bortezomib
• Melphalan
• Prednisone

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Boronic Acids (administration & dosage, adverse effects)
• Bortezomib
• Disease-Free Survival
• Humans
• Kaplan-Meier Estimate
• Melphalan (administration & dosage, adverse effects)
• Multiple Myeloma (drug therapy, mortality)
• Prednisone (administration & dosage, adverse effects)
• Proportional Hazards Models
• Pyrazines (administration & dosage, adverse effects)
• Thalidomide (administration & dosage, adverse effects)
• Treatment Outcome