title: Treatment outcomes in patients with relapsed and refractory multiple myeloma and high-risk cytogenetics receiving single-agent carfilzomib in the PX-171-003-A1 study.
abstract: Several cytogenetic abnormalities are associated with poor outcomes in multiple myeloma (MM). We prospectively analyzed the impact of cytogenetic abnormalities on outcomes during the phase 2 PX-171-003-A1 study of single-agent carfilzomib for relapsed and refractory MM. In the response-evaluable population (257/266), fluorescence in situ hybridization (FISH)/conventional cytogenetic profiles were available for 229 patients; 62 (27.1%) had high-risk cytogenetics--del 17p13, t(4;14) or t(14;16) by interphase FISH or deletion 13 or hypodiploidy by metaphase cytogenetics--and 167 (72.9%) had standard-risk profiles. Generally, baseline characteristics were similar between the subgroups, but International Staging System stage III disease was more common in high- vs standard-risk patients (41.9% vs 27.5%) as was Eastern Cooperative Oncology Group performance status 1/2 (85.5% vs 68.3%). Overall response was comparable between the subgroups (25.8% vs 24.6%, respectively; P=0.85), while time-to-event end points showed a trend of shorter duration in high-risk patients, including median duration of response (5.6 months (95% confidence interval (CI) 3.7-7.8) vs 8.3 months (95% CI 5.6-12.3)) and overall survival (9.3 (95% CI 6.5-13.0) vs 19.0 months (95% CI 15.4-NE); P=0.0003). Taken together, these findings demonstrate that single-agent carfilzomib is efficacious and has the potential to at least partially overcome the impact of high-risk cytogenetics in heavily pre-treated patients with MM.
authors.affiliation: Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Jakubowiak
authors.forename: D S
authors.initials: DS
authors.lastname: Siegel
authors.forename: T
authors.initials: T
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Vij
authors.forename: S
authors.initials: S
authors.lastname: Lonial
authors.forename: S
authors.initials: S
authors.lastname: Trudel
authors.forename: V
authors.initials: V
authors.lastname: Kukreti
authors.forename: N
authors.initials: N
authors.lastname: Bahlis
authors.forename: M
authors.initials: M
authors.lastname: Alsina
authors.forename: A
authors.initials: A
authors.lastname: Chanan-Khan
authors.forename: F
authors.initials: F
authors.lastname: Buadi
authors.forename: F J
authors.initials: FJ
authors.lastname: Reu
authors.forename: G
authors.initials: G
authors.lastname: Somlo
authors.forename: J
authors.initials: J
authors.lastname: Zonder
authors.forename: K
authors.initials: K
authors.lastname: Song
authors.forename: A K
authors.initials: AK
authors.lastname: Stewart
authors.forename: E
authors.initials: E
authors.lastname: Stadtmauer
authors.forename: B L
authors.initials: BL
authors.lastname: Harrison
authors.forename: A F
authors.initials: AF
authors.lastname: Wong
authors.forename: R Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: S
authors.initials: S
authors.lastname: Jagannath
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D009842:Oligopeptides / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; C524865:carfilzomib