1. 1 National and Kapodistrian University of Athens, Athens, Greece; 2 Mayo Clinic, Scottsdale, AZ; 3 Division of Hematology, Mayo Clinic, Rochester, MN; 4 St István and St Laszlo Hospital, Budapest, Hungary; 5 Department of Internal Medicine, General University Hospital in Prague, Prague, Czech Republic; 6 Institut Català d’Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain; 7 University Hospital Brno and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; 8 Hospital Clínic de Barcelona, Barcelona, Spain; 9 John Theurer Cancer Center at Hackensack University, Hackensack, New Jersey; 10 Queen Joanna University Hospital, Sofia, Bulgaria; 11 Hematology Clinic University Multiprofile Hospital for Active Treatment, Plovdiv, Bulgaria; 12 Department of Hematology, Mór Kaposi Teaching Hospital, Kaposvár, Hungary; 13 Hematological Department, First Republican Clinical Hospital of Udmurtia, Izhevsk, Russia; 14 Weill Cornell Medical College, New York, New York; 15 University of Chicago Medical Center, Chicago, IL; 16 Clinica Universidad de Navarra, Spain; 17 Wilhelminen Cancer Research Institute, Wilhelminenspital, Vienna, Austria; 18 Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA, USA; 19 University of Nantes, Nantes, France; 20 University of Torino, Torino, Italy Effect of Carfilzomib, Lenalidomide, and Dexamethasone vs Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma by Line of Therapy: Interim Results From the Phase 3 ASPIRE Study Meletios A. Dimopoulos, 1 A. Keith Stewart, 2 S. Vincent Rajkumar, 3 Tamás Masszi, 4 Ivan Špička, 5 Albert Oriol, 6 Roman Hájek, 7 Laura Rosiñol, 8 David Siegel, 9 Georgi G. Mihaylov, 10 Vesselina Goranova-Marinova, 11 Péter Rajnics, 12 Aleksandr Suvorov, 13 Ruben Niesvizky, 14 Andrzej Jakubowiak, 15 Jesus San-Miguel, 16 Heinz Ludwig, 17 Naseem Zojwalla, 18 Margaret Tonda, 18 Xinqun Yang, 18 Philippe Moreau, 19 Antonio Palumbo 20

2. Introduction Carfilzomib is a selective proteasome inhibitor that is approved in Argentina, Mexico, Israel, and the United States for use in relapsed and refractory multiple myeloma (MM) A preplanned interim analysis of the phase 3 study ASPIRE (N=792) demonstrated that the addition of carfilzomib to lenalidomide and dexamethasone (KRd) led to a significant reduction in the risk of progression or death when compared with lenalidomide and dexamethasone alone (Rd; hazard ratio [HR], 0.69; 95% confidence interval, 0.57–0.83; P<.0001) 1 Herein we present efficacy and safety results from a post hoc secondary analysis of patients who enrolled on the ASPIRE study after first relapse (1 prior line of therapy) compared with those after 2 or more prior lines of therapy 2 1. Stewart AK, et al. N Engl J Med. 2015;372:142–152.

3. Conclusions Results from this post hoc secondary analysis confirm the clinical benefit for using KRd vs Rd for the treatment of patients in their first relapse (1 prior line of therapy) and patients with ≥2 prior lines of therapy The use of KRd led to improvements in PFS in patients with 1 or ≥2 prior lines of therapy ‒ 12-month improvement in median PFS vs Rd in patients with 1 prior line of therapy (HR, 0.69) ‒ 9-month improvement in median PFS vs Rd in patients with ≥2 prior lines of therapy (HR, 0.69) ORRs in the KRd group were significantly higher than in the Rd group ‒ 1 prior line of therapy: 87.0% vs 70.1% (P<.0001) ‒ ≥2 prior lines of therapy; 87.3% vs 64.4% (P<.0001) Nearly 5-fold as many patients with 1 prior line of therapy and nearly 3- fold as many patients with ≥2 prior lines of therapy achieved ≥CR with KRd vs Rd 3

4. Conclusions (continued) Grade ≥3 AEs were reported at similar rates between KRd and Rd groups in patients with 1 and ≥2 prior lines of therapy KRd had a favorable benefit–risk profile compared with Rd after 1 and ≥2 prior lines of therapy in patients with relapsed MM 4

5. Acknowledgments The authors wish to thank all of the patients, families, caregivers, research nurses, study coordinators, and support staff who contributed to this study. This study was supported by Onyx Pharmaceuticals, Inc., an Amgen subsidiary, South San Francisco, CA. Medical writing and editorial assistance was provided by BlueMomentum, an Ashfield Company, part of UDG Healthcare PLC, and funded by Onyx Pharmaceuticals, Inc., an Amgen subsidiary. 5