title: Superior results of Total Therapy 3 (2003-33) in gene expression profiling-defined low-risk multiple myeloma confirmed in subsequent trial 2006-66 with VRD maintenance.
abstract: The Total Therapy 3 trial 2003-33 enrolled 303 newly diagnosed multiple myeloma patients and was noted to provide superior clinical outcomes compared with predecessor trial Total Therapy 2, especially in gene expression profiling (GEP)-defined low-risk disease. We report here on the results of successor trial 2006-66 with 177 patients, using bortezomib, lenalidomide, and dexamethasone maintenance for 3 years versus bortezomib, thalidomide, and dexamethasone in year 1 and thalidomide/dexamethasone in years 2 and 3 in the 2003-33 protocol. Overall survival (OS) and event-free survival (EFS) plots were super-imposable for the 2 trials, as were onset of complete response and complete response duration (CRD), regardless of GEP risk. GEP-defined high-risk designation, pertinent to 17% of patients, imparted inferior OS, EFS, and CRD in both protocols and, on multivariate analysis, was the sole adverse feature affecting OS, EFS, and CRD. Mathematical modeling of CRD in low-risk myeloma predicted a 55% cure fraction (P < .001). Despite more rapid onset and higher rate of CR than in other molecular subgroups, CRD was inferior in CCND1 without CD20 myeloma, resembling outcomes in MAF/MAFB and proliferation entities. The robustness of the GEP risk model should be exploited in clinical trials aimed at improving the notoriously poor outcome in high-risk disease.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Bijay
authors.initials: B
authors.lastname: Nair
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Jackie
authors.initials: J
authors.lastname: Szymonifka
authors.forename: Antje
authors.initials: A
authors.lastname: Hoering
authors.forename: Yazan
authors.initials: Y
authors.lastname: Alsayed
authors.forename: Sarah
authors.initials: S
authors.lastname: Waheed
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics*; D015999:Multivariate Analysis; D011719:Pyrazines / Q000008:administration & dosage; D012307:Risk Factors; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide