title: 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.affiliation: Unitá Operativa Complessa (UOC) Ematologia, Dipartimento Oncoematologico, A.O. di Cosenza, Cosenza, Italy. fortunato_morabito@tin.it
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Carla
authors.initials: C
authors.lastname: Mazzone
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Chiara
authors.initials: C
authors.lastname: Nozzoli
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Giulia
authors.initials: G
authors.lastname: Benevolo
authors.forename: Iolanda
authors.initials: I
authors.lastname: Vincelli
authors.forename: Tommasina
authors.initials: T
authors.lastname: Guglielmelli
authors.forename: Mariella
authors.initials: M
authors.lastname: Grasso
authors.forename: Roberto
authors.initials: R
authors.lastname: Marasca
authors.forename: Luca
authors.initials: L
authors.lastname: Baldini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
authors.forename: Ignazio
authors.initials: I
authors.lastname: Majolino
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.forename: Michele
authors.initials: M
authors.lastname: Cavo
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007674:Kidney Diseases / Q000150:complications* / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D020360:Neoadjuvant Therapy; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone