title: The relationship between quality of response and clinical benefit for patients treated on the bortezomib arm of the international, randomized, phase 3 APEX trial in relapsed multiple myeloma.
abstract: Quality of response is associated with prolonged overall survival (OS) in newly diagnosed multiple myeloma patients. This cohort study within the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of bortezomib versus dexamethasone in relapsed myeloma assessed the relationship between quality of response to bortezomib (n = 315) and clinical benefit. Treatment-free interval (TFI), time to alternative therapy (TTAT), time to progression (TTP) and OS were assessed in response-evaluable patients in the bortezomib arm in cohorts defined by achievement of complete response (CR; n = 27), very good partial response (VGPR; n = 31), partial response (PR; n = 77), minimal response (MR; n = 21) or non-response (NR, including stable and progressive disease; n = 159). CR was associated with significantly longer median TFI (24.1 vs. 6.9/6.4 months) and TTAT (27.1 vs. 13.6/14 months) versus VGPR/PR. Median TTP was similar in CR, VGPR and PR cohorts; median OS was not reached. Patients achieving MR appeared to have prolonged median TFI (3.8 vs. 2.3 months), TTAT (8.7 vs. 6.2 months), TTP (4.9 vs. 2.8 months) and OS (24.9 vs. 18.7 months) versus NR. In conclusion, bortezomib had substantial activity in relapsed myeloma patients; CR may be a surrogate marker for significant clinical benefit with bortezomib. MR appeared to be valid as a separate response category in this setting.
authors.affiliation: Weill-Cornell Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10021, USA. run9001@med.cornell.edu
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Michael W
authors.initials: MW
authors.lastname: Schuster
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Harousseau
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Boral
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Joan
authors.initials: J
authors.lastname: Bladé
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D016009:Chi-Square Distribution; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012074:Remission Induction; D013995:Time; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib