Keith Stewart¹, S. vincent Rajkumar², Meletios a.Dimopoulos³, Tamás Masszi⁴, Ivan Špička⁵, Albert Oriol⁶, Roman Hájek⁷, Laura Rosiñol⁸, David Siegel⁹, Georgi g. Mihaylov¹⁰,

Vesselina Goranova-marinova¹¹, Péter Rajnics¹², Aleksandr Suvorov¹³, Ruben Niesvizky¹⁴, Andrzej j. Jakubowiak¹⁵, Jesus f. San miguel¹⁶, Heinz Ludwig¹⁷, Naseem Zojwalla¹⁸, Margaret e. Tonda¹⁸, BiaoXing¹⁸, Philippe Moreau¹⁹, Antonio Palumbo²⁰

¹Division of Hematology–Oncology, Mayo Clinic, ²Mayo Clinic, ³Alexandra Hospital, ⁴St István and St Laszlo Hospital, ⁵General University Hospital in Prague, ⁶Hospital Germans Trias iPujol, Institut Català d’Oncologia, ⁷University of Ostrava,University Hospital Brno and Faculty of Medicine, ⁸Hospital Clínic deBarcelona, ⁹John Theurer CancerCenter at Hackensack University, ¹⁰Queen Joanna University Hospital, ¹¹Hematology Clinic University Multiprofile Hospital for Active Treatment, ¹²Mór Kaposi Teaching Hospital, ¹³First Republican Clinical Hospital of Udmurtia, ¹⁴Weill Cornell Medical College, ¹⁵University of ChicagoMedical Center, ¹⁶Clinica Universidad de Navarra, ¹⁷Wilhelminenspital, Wilhelminen Cancer Research Institute, ¹⁸Inc., Onyx Pharmaceuticals,¹⁹University of Nantes, ²⁰University of Torino.

Objective:Rd is a reference treatment for patientswith RMM. KRd has shown efficacy in a phase 1/2 study in RMM (Wang et al. Blood2013; 122:3122-3128). The ASPIRE study is comparing KRd with Rd in patientswith RMM. Method: Adults with RMM (1-3 prior regimens; N=792) wererandomized (1:1) to KRd or Rd. All patients received lenalidomide (25mg) ondays (D) 1-21 and dexamethasone (40 mg) on D1, 8, 15, 22 (28-day cycle [C]).KRd patients also received carfilzomib on D1, 2, 8, 9, 15, 16 during C1-12 (20mg/m² [D1, 2 of C1]; 27 mg/m² thereafter); carfilzomibwas omitted on D8, 9 during C13-18 and was not administered beyond C18. Theprimary endpoint is progression-free survival (PFS). Secondary endpointsinclude overall survival (OS), overall response rate (ORR; ≥partial response),duration of response (DOR), health-related quality of life (HR-QoL), andsafety. Result: Median treatment exposure was 22 cycles (KRd) and 14cycles (Rd). PFS was significantly improved with carfilzomib (hazard ratio[HR]=0.69; 95% confidence interval [CI]: 0.57–0.83; P<.0001), with a longer duration of median PFS for KRd vs. Rd(26.3 vs 17.6 months, respectively). Median OS was not reached (HR=0.79, 95%CI,0.63-0.99); Kaplan-Meier 24-month OS event-free rates were 73.3% (KRd) and65.0% (Rd) at an interim analysis. ORRs were 87.1% (KRd) and 66.7% (Rd) (P<.0001); 31.8% (KRd) vs 9.3% (Rd)achieved a ≥complete response; 14.1% and 4.3% achieved a stringent completeresponse. Median DOR was 28.6 (KRd) and 21.2 months (Rd). KRd improved HR-QoLcompared with Rd over 18 cycles of treatment (P=.0001). Grade ≥3 adverse events (AEs) were reported in 83.7% and80.7% of KRd and Rd patients, respectively; 15.3% and 17.7% of patients,respectively, discontinued treatment owing to AEs. Conclusion: Inpatients with RMM, KRd resulted in a clinically meaningful and statisticallysignificant improvement in PFS compared with Rd and had a favorablebenefit-risk profile. Patients continue to be followed for survival.

KeyWords: Carfilzomib, Lenalidomide, Multiplemyeloma