Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment.

Abstract

We assessed efficacy, safety, and reversal of renal impairment (RI) in untreated patients with multiple myeloma given bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide (VMPT-VT) maintenance or bortezomib-melphalan-prednisone (VMP). Exclusion criteria included serum creatinine ≥ 2.5 mg/dL. In the VMPT-VT/VMP arms, severe RI (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min), moderate RI (eGFR 31-50 mL/min), and normal renal function (eGFR > 50 mL/min), were 6%/7.9%, 24.1%/24.9%, and 69.8%/67.2%, respectively. Statistically significant improvements in overall response rates and progression-free survival were observed in VMPT-VT versus VMP arms across renal cohorts, except in severe RI patients. In the VMPT group, severe RI reduced overall survival (OS). RI was reversed in 16/63 (25.4%) patients receiving VMPT-VT versus 31/77 (40.3%) receiving VMP. Multivariate analysis showed male sex (P = .022) and moderate RI (P = .003) significantly predicted RI recovery. VMP patients achieving renal response showed longer OS. In both arms, greater rates of severe hematologic adverse events were associated with RI (eGFR < 50 mL/min), however, therapy discontinuation rates were unaffected. VMPT-VT was superior to VMP for cases with normal renal function and moderate RI, whereas VMPT-VT failed to outperform VMP in patients with severe RI, although the relatively low number of cases analyzed preclude drawing definitive conclusions. VMPT-VT had no advantage in terms of RI reversal over VMP.

• Authors: Fortunato Morabito, Massimo Gentile, Carla Mazzone, Davide Rossi, Francesco Di Raimondo, Sara Bringhen, Roberto Ria, Massimo Offidani, Francesca Patriarca, Chiara Nozzoli, Maria Teresa Petrucci, Giulia Benevolo, Iolanda Vincelli, Tommasina Guglielmelli, Mariella Grasso, Roberto Marasca, Luca Baldini, Vittorio Montefusco, Pellegrino Musto, Nicola Cascavilla, Ignazio Majolino, Caterina Musolino, Michele Cavo, Mario Boccadoro, Antonio Palumbo
• Journal: Blood (Blood) Vol. 118 Issue 22 Pg. 5759-66 (Nov 24 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21951682 (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

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Boronic Acids (administration & dosage, adverse effects)
• Bortezomib
• Female
• Glomerular Filtration Rate
• Humans
• Induction Chemotherapy (methods)
• Kidney Diseases (complications, drug therapy, mortality, physiopathology)
• Maintenance Chemotherapy (methods)
• Male
• Melphalan (administration & dosage, adverse effects)
• Multiple Myeloma (complications, drug therapy, mortality, physiopathology)
• Neoadjuvant Therapy
• Prednisone (administration & dosage, adverse effects)
• Pyrazines (administration & dosage, adverse effects)
• Survival Analysis
• Thalidomide (administration & dosage, adverse effects)
• Treatment Outcome