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.

Centre de Recherche en Cancérologie de Toulouse INSERM U1037 Toulouse France; L'Institut Universitaire du Cancer de Toulouse Oncopole Centre Hospitalier Universitaire Toulouse France;

Charles University Faculty Hospital and Faculty of Medicine Hradec Králové Czech Republic;

Department of Hemato oncology University Hospital Olomouc Olomouc Czech Republic;

Department of Internal Medicine University Hospital Praha Czech Republic;

Fred Hutchinson Cancer Research Center Seattle WA;

Hadassah Hebrew University Medical Center Jerusalem Israel;

Hematology Clinic University Multiprofile Hospital for Active Treatment Sv Georgi and Medical University Plovdiv Bulgaria;

Hospital Clínic de Barcelona Barcelona Spain;

Institut Català d'Oncologia Institut Josep Carreras Hospital Germans Trias i Pujol Barcelona Spain;

John Theurer Cancer Center at Hackensack University Hackensack NJ;

Mayo Clinic Scottsdale AZ;

National and Kapodistrian University of Athens Athens Greece;

Onyx Pharmaceuticals Inc South San Francisco CA; and

Princess Margaret Cancer Centre Toronto ON Canada;

Queen Joanna University Hospital Sofia Bulgaria;

St István and St Laszlo Hospital Budapest Hungary;

The University of Texas MD Anderson Cancer Center Houston TX;

University Hospital of Salamanca Instituto de Investigación Biomédica de Salamanca Salamanca Spain;

University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic;

University of Chicago Medical Center Chicago IL;

University of Nantes Nantes France

University of Torino Torino Italy;

Weill Cornell Medical College New York Presbyterian Hospital New York NY;

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ClinicalTrials.gov
NCT01080391