title: Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients.
abstract: PURPOSE To evaluate the effect of bortezomib as induction therapy before autologous transplantation, followed by lenalidomide as consolidation-maintenance in myeloma patients. PATIENTS AND METHODS Newly diagnosed patients age 65 to 75 years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD]) included four 21-day cycles of bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11), pegylated liposomal doxorubicin (30 mg/m(2) on day 4), and dexamethasone (40 mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Autologous transplantation was tandem melphalan 100 mg/m(2) (MEL100) and stem-cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse. Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs]) and efficacy (response rate). Results A total of 102 patients were enrolled. In a per-protocol analysis, after PAD, 58% of patients had very good partial response (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year progression-free survival rate was 69%, and the 2-year overall survival rate was 86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%), and pneumonia (10%). During consolidation-maintenance, grade 3 to 4 AEs were neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash (4%). CONCLUSION Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance, is an effective regimen.
authors.affiliation: Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero-Universitaria San Giovanni Battista, Via Genova 3, 10126 Torino, Italy. appalumbo@yahoo.com
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.forename: Patrizia
authors.initials: P
authors.lastname: Falco
authors.forename: Claudia
authors.initials: C
authors.lastname: Crippa
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Fausto
authors.initials: F
authors.lastname: Rossini
authors.forename: Simona
authors.initials: S
authors.lastname: Caltagirone
authors.forename: Giulia
authors.initials: G
authors.lastname: Benevolo
authors.forename: Norbert
authors.initials: N
authors.lastname: Pescosta
authors.forename: Tommasina
authors.initials: T
authors.lastname: Guglielmelli
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Anna Marina
authors.initials: AM
authors.lastname: Liberati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rossi
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D017024:Chemotherapy, Adjuvant; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D020360:Neoadjuvant Therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011241:Prednisone / Q000008:administration & dosage; D011480:Protease Inhibitors / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D033581:Stem Cell Transplantation; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone