Carfilzomib-lenalidomide-dexamethasone versus - PowerPoint PPT Presentation

Carfilzomib-lenalidomide-dexamethasone versus bortezomib-lenalidomide-dexamethasone in newly diagnosed multiple myeloma: results from a prospective, longitudinal, observational (CoMMpass) study Ola Landgren, 1 David Siegel, 2 Daniel Auclair, 3 Ajai Chari, 4 Michael Boedigheimer, 5 Tim Welliver, 5 Khalid Mezzi, 5 Karim Iskander, 5 Andrzej Jakubowiak 6 1 Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY ; 2 John Theurer Cancer Center, Myeloma and Lymphoma Divisions, Hackensack University Medical Center, Hackensack, NJ; 3 Multiple Myeloma Research Foundation (MMRF), Middletown, CT; 4 Department of Hematology and Medical Oncology, Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY; 5 Amgen Inc., Thousand Oaks, CA; 6 University of Chicago, Chicago, IL

Background • Triplet regimens incorporating a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) are a standard-of-care for patients with newly diagnosed Multiple Myeloma (NDMM) • Carfilzomib-lenalidomide-dexamethasone (KRd) and bortezomib- lenalidomide-dexamethasone (VRd) are NDMM treatment options listed by NCCN Guidelines • Currently, there are no data from randomized, controlled trials comparing KRd to VRd in patients with NDMM

The MMRF CoMMpass Study • CoMMpass: Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile • Key Inclusion Criteria: – Patients with NDMM from Q3 2011 – Patients treated with an IMiD and/or a PI as part of the initial regimen • Site Participation: 90 sites in Canada, Italy, Spain, and USA • Enrollment: 1143 patients; both real-world and from investigator- sponsored studies

Study Design (Data From CoMMpass IA14) Primary Outcome Total CoMMpass Population 1143 patients enrolled • Event-free survival: progression, death, or change in line of therapy; Population Available for whichever came first Comparison 151 KRd and 489 VRd in NDMM Secondary Outcomes • Objective response rate Propensity-Score Matching* • Age, Gender, ISS Staging, and Renal Rate of treatment Insufficiency discontinuation due to adverse events Matched Population 151 KRd and 151 VRd *Missing data prevented matching based on Cytogenetic Risk

Patient Characteristics KRd VRd Characteristic (N = 151) (N = 151) Age, median (range) 58 (38–74) 59 (38-74) Gender, n (%) Female 56 (37) 48 (32) Male 95 (63) 103 (68) ISS stage, n (%) I 72 (48) 73 (48) II 60 (40) 57 (38) III 19 (12) 21 (14) Transplant received, n (%) Yes 78 (52) 106 (70) No 73 (48) 45 (30) Cytogenetic risk, n (%) Standard 14 (9) 60 (40) High 30 (20) 29 (19) Missing 107 (71) 62 (41)

Event-free Survival 1 EFS Landmark Analyses 0.8 Event-free Survival 12-Month 18-Month KRd 90% 87% 0.6 KRd (N=151) VRd (N=150) VRd 78% 72% 0.4 Median Follow-Up HR (95% CI): 0.35 (0.19 to 0.64) 0.2 • KRd: 12 months p-value: <0.001 • VRd: 49 months 0 0 6 12 18 24 Time (months) Patients at risk KRd 151 117 67 37 23 VRd 150 126 115 103 90

Event-free Survival by Stem Cell Transplant Transplant No Transplant 1 1 0.8 0.8 Event-free Survival Event-free Survival KRd (N=78) VRd (N=103) 0.6 0.6 0.4 0.4 KRd (N=73) VRd (N=47) 0.2 HR (95% CI): 0.49 (0.25 to 0.97) 0.2 HR (95% CI): 0.46 (0.23 to 0.91) p-value: 0.037 p-value: 0.022 0 0 0 6 12 18 24 0 6 12 18 24 Time (months) Time (months) Pts at risk Pts at risk KRd 78 70 47 28 18 KRd 73 47 20 9 5 VRd 103 94 89 82 72 VRd 47 32 26 21 18

Best Clinical Response at 12 Months 80 KRd VRd 80 70 64 Response Rate (%) 60 54 40 23 20 15 0 Objective Response ≥VGPR ≥CR

Treatment Discontinuation Due to Adverse Events KRd VRd Timepoint (N = 151) (N = 151) Overall 4.0% 4.6% 0 to 6 months 2.0% 2.6% 0 to 12 months 2.0% 3.3%

NDMM Studies With KRd or VRd KRd Studies VRd Studies Best 1-year 2-year Best 1-year 2-year Study N Response PFS PFS Study N Response PFS PFS UMMC 64% ≥CR SWOG S0777 16% ≥CR 53 100% 91% 216 ~84% ~70% Jakubowiak et al. 1 87% ≥VGPR Durie et al. 5 44% ≥VGPR MMRC 78% ≥CR 48% ≥CR 76 97% 94% 350 ~90% ~78% Zimmerman et al. 2 91% ≥VGPR 77% ≥VGPR IFM 09 Attal et al. 6 NCI 67% ≥CR 59% ≥CR 45 ~96% ~84% 350 ~85% ~68% Korde et al. 3 91% ≥VGPR 87% ≥VGPR IFM 69% ≥CR PETHEMA/GEM 58% ≥CR 43 ~95% ~91% 458 ~90% ~82% Roussel et al. 4 93% ≥VGPR Rosinol et al. 7 78% ≥VGPR Patients Did Not Receive Transplant Patients Received Transplant 1. Jakubowiak AJ, et al. Blood. 2012;120:1801-1809. 2. Zimmerman T, et al. Presented at ASH 2016. 3. Korde N, et al. JAMA Oncol. 2015;1(6):746-754. 4. Roussel M, et al. Presented at ASH 2016. 5. Durie GM, et al. Lancet Oncol. 2017; 389:519-527. 6. Attal M, et al. N Engl J Med. 2017; 376:1311-1320. 7. Rosinol L et al. Presented at ASH 2018.

Limitations • Unblinded, non-randomized study with clinician-assessed response • Missing data prevented matching based on ECOG Score and Cytogenetic Risk Group • Differences in patient characteristics – Higher percentage of VRd patients received stem cell transplantation – Higher percentage of KRd patients had high-risk cytogenetics based on available data • Shorter median follow-up for KRd as compared to VRd • Full safety data not available

Summary • In patients with NDMM, KRd (versus VRd) treatment led to significant improvements in EFS. A consistent benefit was seen in both transplanted and non-transplanted patients • Patients treated with KRd demonstrated higher response rates and increased depth of response • KRd and VRd had similar treatment discontinuation rates due to adverse events suggesting similar tolerability • This analysis from the CoMMpass study shows that KRd compares favorably to VRd in patients with NDMM. Randomized studies comparing KRd and VRd are ongoing

Acknowledgements • We would like to thank the patients and healthcare providers who participated in the CoMMpass study. • We would like to thank Julie Blaedel , Alan Fu , Richard Hu , Shawn Lee , Jesse Potash , and Akeem Yusuf for their contributions to this presentation.

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Conflict of Interest Disclosures Ola Landgren Amgen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria; Merck: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Binding Site: Consultancy, Honoraria; Adaptive: Consultancy, Honoraria; Cellectis: Consultancy; Glenmark: Consultancy, Research Funding; Juno: Consultancy; Seattle Genetics: Research Funding. David Siegel Novartis: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Speakers Bureau. Daniel Auclair No disclosures Ajai Chari Celgene: Consultancy, Membership on Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Membership on Board of Directors or advisory committees; Takeda: Consultancy, Membership on Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on Board of Directors or advisory committees, Research Funding; Array Biopharma: Research Funding; Adaptive Biotechnology: Membership on Board of Directors or advisory committees; The Binding Site: Consultancy; Bristol Myers Squibb: Consultancy. Michael Boedigheimer Employee of and owns stock in Amgen. Timothy Welliver Employee of and owns stock in Amgen. Khalid Mezzi Employee of and owns stock in Amgen. Karim Iskander Employee of and owns stock in Amgen. Andrzej Jakubowiak Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; SkylineDx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

Event-free Survival 1 90% 87% KRd (N=151) Median Follow-Up VRd (N=150) • KRd: 12 months 0.8 78% Event-free Survival • 72% VRd: 49 months 0.6 0.4 0.2 HR (95% CI): 0.35 (0.19 to 0.64) p-value: <0.001 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Time (months) Patients at risk 67 37 23 21 KRd 151 117 17 14 8 2 0 0 0 115 103 91 78 VRd 150 126 57 44 30 19 10 4 0

Event-free Survival 1 90% 87% Hazard Ratios (KRd/VRd) Over Time All No 0.8 Event-free Survival 78% Patients Transplant Transplant 72% 12 0.41 0.20 0.37 Months 0.6 18 0.36 0.25 0.31 Months 0.4 24 0.50 0.47 0.39 Months Overall 0.35 0.49 0.46 0.2 KRd 52% of KRd patients received transplant 70% of VRd patients received transplant VRd 0 0 6 12 18 24 Time (months) Patients at risk KRd 151 117 67 37 23 VRd 150 126 115 103 90