BACKGROUND: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established. METHODS: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization. Cumulative rates of complete response (CR) or better over time and PFS hazard ratio (HR) at 18 months were evaluated for KRd versus Rd. PFS HRs were also assessed according to cytogenetic risk, prior lines of therapy, and prior bortezomib treatment. Cox regression analysis was used to evaluate PFS HRs. RESULTS: The hazard ratio (HR) for PFS at 18 months was 0.58 versus 0.69 for the overall ASPIRE study. Patients with high-risk cytogenetics, ≥ 1 prior lines of therapy, and prior bortezomib exposure benefited from KRd up to 18 months versus Rd. The HRs for PFS at 18 months in the pre-defined subgroups were lower than those in the overall study. The difference in the proportion of KRd and Rd patients achieving at least a complete response (CR) increased dramatically over the first 18 months and then remained relatively constant. The safety profile at 18 months was consistent with previous findings. CONCLUSIONS: The improved PFS HR at 18 months and the continued increase in CR rates for KRd through 18 cycles suggest that there may be a benefit of continued carfilzomib treatment. TRIAL REGISTRATION: Clinical trials.gov NCT01080391 . Registered 2 March 2010.

Amgen Inc Thousand Oaks CA USA

Faculty Hospital and Medical Faculty of Charles University in Hradec Kralove Hradec Kralove Czech Republic

Fred Hutchinson Cancer Research Center Seattle WA USA

Hospital Clinico Universitario de Salamanca IBSAL Salamanca Spain

School of Medicine National and Kapodistrian University of Athens Athens Greece

The University of Texas MD Anderson Cancer Center Houston TX USA

University Hospital Olomouc Medical Faculty of Palacky University Olomouc Olomouc Czech Republic

University of Nantes Nantes France

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NCT01080391