title: Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.
abstract: The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391.
authors.affiliation: Centre de Recherche en Cancérologie de Toulouse INSERM U1037, Toulouse, France; L'Institut Universitaire du Cancer de Toulouse-Oncopole, Centre Hospitalier Universitaire, Toulouse, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Avet-Loiseau
authors.affiliation: Mayo Clinic, Scottsdale, AZ;
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: John Theurer Cancer Center at Hackensack University, Hackensack, NJ;
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.affiliation: National and Kapodistrian University of Athens, Athens, Greece;
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Internal Medicine, University Hospital, Praha, Czech Republic;
authors.forename: Ivan
authors.initials: I
authors.lastname: Špička
authors.affiliation: St. István and St. Laszlo Hospital, Budapest, Hungary;
authors.forename: Tamás
authors.initials: T
authors.lastname: Masszi
authors.affiliation: University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic;
authors.forename: Roman
authors.initials: R
authors.lastname: Hájek
authors.affiliation: Hospital Clínic de Barcelona, Barcelona, Spain;
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.affiliation: Hematology Clinic University Multiprofile Hospital for Active Treatment "Sv. Georgi" and Medical University, Plovdiv, Bulgaria;
authors.forename: Vesselina
authors.initials: V
authors.lastname: Goranova-Marinova
authors.affiliation: Queen Joanna University Hospital, Sofia, Bulgaria;
authors.forename: Georgi
authors.initials: G
authors.lastname: Mihaylov
authors.affiliation: Charles University Faculty Hospital and Faculty of Medicine, Hradec Králové, Czech Republic;
authors.forename: Vladimír
authors.initials: V
authors.lastname: Maisnar
authors.affiliation: University Hospital of Salamanca/Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain;
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY;
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.affiliation: Institut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain;
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: University of Chicago Medical Center, Chicago, IL;
authors.forename: Andrzej
authors.initials: A
authors.lastname: Jakubowiak
authors.affiliation: Department of Hemato-oncology, University Hospital Olomouc, Olomouc, Czech Republic;
authors.forename: Jiri
authors.initials: J
authors.lastname: Minarik
authors.affiliation: University of Torino, Torino, Italy;
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: William
authors.initials: W
authors.lastname: Bensinger
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON, Canada;
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.affiliation: Hadassah-Hebrew University Medical Center, Jerusalem, Israel;
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.affiliation: Mayo Clinic, Scottsdale, AZ;
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.affiliation: Onyx Pharmaceuticals Inc., South San Francisco, CA; and.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Obreja
authors.affiliation: University of Nantes, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D009842:Oligopeptides / Q000008:administration & dosage; D012008:Recurrence; D012307:Risk Factors; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D009842:Oligopeptides; D013792:Thalidomide; C524865:carfilzomib; D003907:Dexamethasone; D000077269:Lenalidomide