Welcome participants at UH Seidman Cancer Center Clinical - PowerPoint PPT Presentation

Welcome participants at UH Seidman Cancer Center Clinical Investigator Perspectives on the Current and Future Management of Multiple Myeloma A Meet The Professor Series Sagar Lonial, MD Chair and Professor Department of Hematology and Medical Oncology Anne and Bernard Gray Family Chair in Cancer Chief Medical Officer Winship Cancer Institute Emory University School of Medicine Atlanta, Georgia Co-provided by

Meet The Professor Program Steering Committee Rafael Fonseca, MD Ola Landgren, MD, PhD Getz Family Professor of Cancer Professor of Medicine Chair, Department of Internal Medicine Chief, Myeloma Service Mayo Clinic Arizona Department of Medicine Scottsdale, Arizona Memorial Sloan Kettering Cancer Center New York, New York Sagar Lonial, MD Shaji K Kumar, MD Chair and Professor Professor of Medicine Department of Hematology Consultant and Medical Oncology Division of Hematology and Blood and Anne and Bernard Gray Family Marrow Transplantation Chair in Cancer Mayo Clinic Chief Medical Officer Rochester, Minnesota Winship Cancer Institute Emory University School of Medicine Atlanta, Georgia Co-provided by

Meet The Professor Program Steering Committee Nikhil C Munshi, MD Noopur Raje, MD Professor of Medicine Director Harvard Medical School Center for Multiple Myeloma Director of Basic and Correlative Massachusetts General Hospital Science Cancer Center Associate Director, Jerome Lipper Professor of Medicine Multiple Myeloma Center Harvard Medical School Department of Medical Oncology Boston, Massachusetts Dana-Farber Cancer Institute Nina Shah, MD Boston, Massachusetts Associate Professor of Medicine University of California Robert Z Orlowski, MD, PhD Florence Maude Thomas Cancer San Francisco Research Professor Division of Hematology-Oncology San Francisco, California Department of Lymphoma and Myeloma Professor, Department of Project Chair Experimental Therapeutics Neil Love, MD Director, Myeloma Section Research To Practice Division of Cancer Medicine Miami, Florida The University of Texas MD Anderson Cancer Center Houston, Texas Co-provided by

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Management of Multiple Myeloma (MM) Module 1: Clinical Decision-Making for Patients with Newly Diagnosed MM (NDMM) • Daratumumab-containing front-line therapy (CASSIOPEIA, MAIA, GRIFFIN) Minimal residual disease (MRD) testing and use in treatment decision-making • Consolidation and maintenance therapy; emerging data with ixazomib • (TOURMALINE-MM3, TOURMALINE-MM4) • Recent relevant datasets Module 2: Contemporary Management of Relapsed/Refractory MM Data with daratumumab-containing regimens; split dosing • Combination regimens with ixazomib (TOURMALINE-MM1) • Recent FDA approval of selinexor and pivotal data from STORM • Recent FDA approval of anti-CD38 isatuximab plus pomalidomide/low-dose • dexamethasone and pivotal data from ICARIA-MM Recent relevant datasets • Module 3: Novel Agents in Late-Stage Development Belantamab mafodotin (DREAMM-2) • • Clinical development of other anti-BCMA agents • Recent relevant datasets Co-provided by

Recent Relevant Datasets Co-provided by

Carfilzomib, Lenalidomide, and Dexamethasone (KRd) versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) for Initial Therapy of Newly Diagnosed Multiple Myeloma (NDMM): Results of ENDURANCE (E1A11) Phase III Trial Kumar S et al. ASCO 2020;Abstract LBA3. (Plenary) Co-provided by

ENDURANCE (E1A11): Treatment-Related AEs Kumar S et al. ASCO 2020;Abstract LBA3. Co-provided by

ENDURANCE (E1A11): TEAEs of Interest Berdeja JG. ASCO 2020 Discussant. Co-provided by

ENDURANCE (E1A11): Treatment-Related AEs (≥2%) Co-provided by Kumar S et al. ASCO 2020;Abstract LBA3.

Primary Analysis of the Randomized Phase II Trial of Bortezomib, Lenalidomide, Dexamthasone with/without Elotuzumab for Newly Diagnosed, High-Risk Multiple Myeloma (SWOG-1211) Usmani SZ et al. ASCO 2020;Abstract 8507. Co-provided by

Depth of Response to Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (Isa-KRd) in Front-Line Treatment of High-Risk Multiple Myeloma: Interim Analysis of the GMMG- CONCEPT Trial Weisel K et al. ASCO 2020;Abstract 8508. Co-provided by

Audience Polling Co-provided by

Currently, what is your usual pretransplant induction regimen for a 65-year-old patient with MM and no high-risk features? 1. RVD (lenalidomide/bortezomib/dexamethasone) 2. KRd (carfilzomib/lenalidomide/dexamethasone) 3. CyBorD 4. MVP, MPR or MPT (M = melphalan, P = prednisone, V = bortezomib, R = lenalidomide, T = thalidomide) 5. MVP/daratumumab 6. Rd/daratumumab 7. VTd (bortezomib/thalidomide/dexamethasone) with daratumumab 8. RVD/daratumumab 9. KRd/daratumumab 10. Other Co-provided by

Currently, what pretransplant induction regimen would you recommend for a 65-year-old patient with multiple myeloma (MM)? Standard risk Del(17p) KRd RVD RVD RVD/daratumumab KRd KRd RVD/daratumumab KRd RVD RVD/daratumumab KRd KRd RVD KRd ± daratumumab RVD KRd Co-provided by

GRIFFIN Randomized Phase II Study Design Consolidation Induction Maintenance Cycles 5-6 Cycles 1-4 Cycles 7-32 T D-RVd D-RVd D-R R Key Eligibility A N • Transplant-eligible R S NDMM 1:1 (N = 223) P • 18-70 years old L • ECOG 0-2 A R RVd RVd N T 21-day cycles 21-day cycles 28-day cycles Primary endpoint: Stringent CR by end of consolidation Voorhees P et al. IMW 2019;Abstract 906. www.clinicaltrials.gov. Accessed January 23, 2020 Co-provided by (NCT02874742).

GRIFFIN Primary Endpoint: sCR at the End of Consolidation PR VGPR CR sCR ORR: p = 0.0160 ORR = 99.0% 100 100 ORR = 91.8% sCR odds ratio: 1.57 90 90 p = 0.068 80 80 42.4 32.0 ≥CR: ≥CR: 70 70 51.5% 42.3% Patients (%) Patients (%) 60 60 10.3 9.1 50 50 ≥VGPR: ≥VGPR: 73.2% 40 40 90.9% 30.9 30 30 39.4 42.4% 20 20 32.0% 10 10 18.6 8.1 0 0 D-RVd RVd D-RVd RVd (n = 99) (n = 97) (n = 99) (n = 97) Voorhees P et al. IMW 2019;Abstract 906. Co-provided by

GRIFFIN: Depth of Response Over Time D-RVd RVd 100 7.2 12.1 ≥CR: 14.4 6.2 90 ≥CR: ≥CR: 21.2 13.4% ≥CR: 7.1 19.2% 19.6% 32.0 5.2 27.3% 37.1 80 42.4 ≥CR: 6.1 ≥CR: ≥CR: 42.3% 49.5 47.4% 70 51.5% ≥CR: 43.3 10.3 62.6% 60 Patients (%) 10.3 46.4 52.5 9.1 50 13.1 30.9 59.6 40 26.8 30 39.4 35.1 29.3 25.8 20 18.6 26.3 17.5 10 12.1 8.1 7.1 2.0 1.0 1.0 1.0 8.2 8.2 8.2 8.2 0 End of End of End of Clinical End of End of End of Clinical induction ASCT consolidation cutoff induction ASCT consolidation cutoff SD/PD/NE PR VGPR CR sCR Voorhees P et al. IMW 2019;Abstract 906. Co-provided by

Regulatory and reimbursement issues aside , what is your preferred induction regimen for an 85-year-old patient with ISS Stage II MM who is transplant ineligible? Standard risk, normal renal function Del(17p) Rd/dara RVD Rd/dara RVD lite Rd/dara RVD lite Rd/dara RVD lite Rd RVD lite RVD or RVD lite RVD lite RVD or RVD lite or Rd/dara RVD lite RVD or RVD lite or Rd/dara RVD lite or KRd Dara = daratumumab Co-provided by

N Engl J Med 2019;380(22):2104-15. Co-provided by

MAIA Primary Endpoint: Progression-Free Survival NDMM Transplant Ineligible 100 30 mo 80 71% D-Rd Progression-free survival Median: Not reached 60 56% HR: 0.56 40 p < 0.001 Rd 20 Median: 31.9 mo 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 Months Facon T et al. N Engl J Med 2019;380(22):2104-15. Co-provided by

MAIA: Overall Response Rate and MRD (NGS; 10 -5 Sensitivity Threshold) Rate p < 0.001 p < 0.001 3.4X 100 30 ORR = 93% 90 ORR = 81% 24% MRD-negative rate, % 25 ≥CR: 80 30 12.5 48% ≥CR: 70 20 25% 12.5 60 ORR, % 17 50 15 28 ≥VGPR: 40 53% 10 ≥VGPR: 30 32 7% 79% 20 5 28 10 14 0 0 D-Rd Rd D-Rd Rd (n = 368) (n = 369) (n = 368) (n = 369) PR VGPR CR sCR Facon T et al. N Engl J Med 2019;380(22):2104-15. Co-provided by

Are there situations in which you believe community- based oncologists/hematologists should be ordering minimal residual disease (MRD) assessment to guide treatment decision-making for patients with MM? Yes – Pts in long-term CR or with plasmacytomas; monitoring amyloidosis Yes – Pts with high-risk disease Yes – After combination therapy; if MRD-negative, collect and store stem cells. Then go straight to maintenance No Yes – Post-transplant, at CR, before and during maintenance Yes, timing the number of induction cycles prior to stem cell collection for patients in CR No No, I don’t believe this test should be ordered in the community to make clinical decisions Co-provided by