title: Sustained complete remissions in multiple myeloma linked to bortezomib in total therapy 3: comparison with total therapy 2.
abstract: Total therapy 3 (TT3), incorporating bortezomib up-front into a tandem transplant regimen for newly diagnosed multiple myeloma (MM), effected 2-year complete response (CR) estimates >90%, which appeared superior to results reported for total therapy 2 (TT2). With median follow-up times of 2 years with TT3 and 5 years with TT2, the clinical outcomes of 303 patients in the former and 668 in the latter trial were compared, including the subset of 607 patients with gene expression profiling (GEP) data. With similar baseline prognostic factors, event-free survival (EFS) (P = 0.0002) and CR duration (P = 0.003) were superior with TT3 vs. TT2 with a strong trend noted also for improved overall survival (OS) (P = 0.16). In the GEP-defined FGFR3 subgroup, TT3 imparted significantly superior OS, EFS and CR duration vis-à-vis TT2. Matching 300 patients each by standard prognostic factors, TT3 yielded superior EFS and CR duration and borderline superior OS. The advantage of TT3 still pertained when the comparison was limited to patients who completed TT2 consolidation rapidly within 24 months. Our data strongly suggest that the addition of bortezomib in TT3 was accountable for its superior performance rather than greater compliance with protocol completion as a result of greater dose-density in TT3 vs. TT2.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Pineda-Roman
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Jeff
authors.initials: J
authors.lastname: Haessler
authors.forename: Elias
authors.initials: E
authors.lastname: Anaissie
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
authors.forename: Frits
authors.initials: F
authors.lastname: van Rhee
authors.forename: John
authors.initials: J
authors.lastname: Crowley
authors.forename: John D
authors.initials: JD
authors.lastname: Shaughnessy
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; D003131:Combined Modality Therapy; D004812:Epidemiologic Methods; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib