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 Jakubowiak6

1Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; 2John

Theurer Cancer Center, Myeloma and Lymphoma Divisions, Hackensack University Medical Center, Hackensack, NJ; 3Multiple Myeloma Research Foundation (MMRF), Middletown, CT; 4Department of Hematology and Medical Oncology, Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY; 5Amgen Inc., Thousand Oaks, CA;

6University of Chicago, Chicago, IL

• 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

Background

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)

Total CoMMpass Population 1143 patients enrolled Population Available for Comparison 151 KRd and 489 VRd in NDMM Propensity-Score Matching* Age, Gender, ISS Staging, and Renal Insufficiency

Matched Population 151 KRd and 151 VRd

*Missing data prevented matching based on Cytogenetic Risk

Primary Outcome

• Event-free survival:

progression, death, or change in line of therapy; whichever came first Secondary Outcomes

• Objective response rate
• Rate of treatment

discontinuation due to adverse events

Patient Characteristics

Characteristic KRd (N = 151) VRd (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

Median Follow-Up

• KRd: 12 months
• VRd: 49 months

6 12 18 24

Time (months)

0.2 0.4 0.6 0.8 1

Event-free Survival

VRd (N=150) KRd (N=151)

150 126 115 103 90 VRd 151 117 67 37 23 KRd Patients at risk

HR (95% CI): 0.35 (0.19 to 0.64) p-value: <0.001 12-Month 18-Month KRd 90% 87% VRd 78% 72% EFS Landmark Analyses

Event-free Survival by Stem Cell Transplant

Transplant

VRd (N=103) KRd (N=78) 6 12 18 24

Time (months)

0.2 0.4 0.6 0.8 1

Event-free Survival

103 94 89 82 72 VRd 78 70 47 28 18 KRd Pts at risk

HR (95% CI): 0.49 (0.25 to 0.97) p-value: 0.037

No Transplant

0.2 0.4 0.6 0.8 1

Event-free Survival

6 12 18 24

Time (months)

VRd (N=47) KRd (N=73)

HR (95% CI): 0.46 (0.23 to 0.91) p-value: 0.022

47 32 26 21 18 VRd 73 47 20 9 5 KRd Pts at risk

Best Clinical Response at 12 Months

80 70 23 64 54 15 20 40 60 80 Objective Response ≥VGPR ≥CR Response Rate (%) KRd VRd

Treatment Discontinuation Due to Adverse Events

Timepoint KRd (N = 151) VRd (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

Study N Best Response 1-year PFS 2-year PFS UMMC Jakubowiak et al.1 53 64% ≥CR 87% ≥VGPR 100% 91% MMRC Zimmerman et al.2 76 78% ≥CR 91% ≥VGPR 97% 94% NCI Korde et al.3 45 67% ≥CR 91% ≥VGPR ~96% ~84% IFM Roussel et al.4 43 69% ≥CR 93% ≥VGPR ~95% ~91% Study N Best Response 1-year PFS 2-year PFS SWOG S0777 Durie et al.5 216 16% ≥CR 44% ≥VGPR ~84% ~70% IFM 09 Attal et al.6 350 48% ≥CR 77% ≥VGPR ~90% ~78% 350 59% ≥CR 87% ≥VGPR ~85% ~68% PETHEMA/GEM Rosinol et al.7 458 58% ≥CR 78% ≥VGPR ~90% ~82%

KRd Studies VRd Studies

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.

• 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

Limitations

• 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

Summary

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.

Back-Up Slides

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

6 12 18 24 30 36 42 48 54 60 66 72 0.2 0.4 0.6 0.8 1 VRd (N=150) KRd (N=151)

Time (months) Event-free Survival

150 115 91 44 19 4 VRd 151 67 23 14 2 KRd Patients at risk 117 126 37 103 17 57 8 30 10 78 21

HR (95% CI): 0.35 (0.19 to 0.64) p-value: <0.001

90% 87% 78% 72%

Median Follow-Up

• KRd: 12 months
• VRd: 49 months

Event-free Survival

All Patients Transplant No Transplant 12 Months 0.41 0.20 0.37 18 Months 0.36 0.25 0.31 24 Months 0.50 0.47 0.39 Overall 0.35 0.49 0.46

Hazard Ratios (KRd/VRd) Over Time

52% of KRd patients received transplant 70% of VRd patients received transplant

6 12 18 24

Time (months)

0.2 0.4 0.6 0.8 1

Event-free Survival

VRd KRd

150 126 115 103 90 VRd 151 117 67 37 23 KRd Patients at risk

90% 87% 78% 72%

Best Response Over Time

ORR, % Rate of ≥VGPR, % Rate of ≥CR, % KRd VRd KRd VRd KRd VRd 6 Months 58 43 48 34 7 4 12 Months 80 64 70 54 23 15 18 Months 87 80 77 70 29 25 Overall 91 93 81 82 32 35 ORR, % Rate of ≥VGPR, % Rate of ≥CR, % KRd VRd KRd VRd KRd VRd 6 Months 56 43 47 35 9 4 12 Months 75 66 68 57 36 16 18 Months 85 84 80 76 60 28

Traditional Conditional (Adjusted for follow-up)