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Blood. 2016 Sep 1;128(9):1174-80. doi: 10.1182/blood-2016-03-707596. Epub 2016 Jul 20.

Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

Author information

1
Centre de Recherche en Cancérologie de Toulouse INSERM U1037, Toulouse, France; L'Institut Universitaire du Cancer de Toulouse-Oncopole, Centre Hospitalier Universitaire, Toulouse, France;
2
Mayo Clinic, Scottsdale, AZ;
3
John Theurer Cancer Center at Hackensack University, Hackensack, NJ;
4
National and Kapodistrian University of Athens, Athens, Greece;
5
Department of Internal Medicine, University Hospital, Praha, Czech Republic;
6
St. István and St. Laszlo Hospital, Budapest, Hungary;
7
University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic;
8
Hospital Clínic de Barcelona, Barcelona, Spain;
9
Hematology Clinic University Multiprofile Hospital for Active Treatment "Sv. Georgi" and Medical University, Plovdiv, Bulgaria;
10
Queen Joanna University Hospital, Sofia, Bulgaria;
11
Charles University Faculty Hospital and Faculty of Medicine, Hradec Králové, Czech Republic;
12
University Hospital of Salamanca/Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain;
13
The University of Texas MD Anderson Cancer Center, Houston, TX;
14
Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY;
15
Institut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trias i Pujol, Barcelona, Spain;
16
University of Chicago Medical Center, Chicago, IL;
17
Department of Hemato-oncology, University Hospital Olomouc, Olomouc, Czech Republic;
18
University of Torino, Torino, Italy;
19
Fred Hutchinson Cancer Research Center, Seattle, WA;
20
Princess Margaret Cancer Centre, Toronto, ON, Canada;
21
Hadassah-Hebrew University Medical Center, Jerusalem, Israel;
22
Onyx Pharmaceuticals Inc., South San Francisco, CA; and.
23
University of Nantes, Nantes, France.

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.

PMID:
27439911
PMCID:
PMC5009511
DOI:
10.1182/blood-2016-03-707596
[Indexed for MEDLINE]
Free PMC Article

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