Welcome participants at Lankenau Medical Center Co-provided by - PowerPoint PPT Presentation

Welcome participants at Lankenau Medical Center 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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Clinical Investigator Perspectives on the Current and Future Management of Multiple Myeloma A Meet The Professor Series Nina Shah, MD Associate Professor of Medicine University of California, San Francisco Division of Hematology-Oncology San Francisco, California Co-provided by

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) 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 Module 3: Novel Agents in Late-Stage Development Belantamab mafodotin (DREAMM-2) • Clinical development of other anti-BCMA agents • Co-provided by

Case Presentation Co-provided by

81-year-old frail woman Kappa light chain multiple myeloma with lytic bone lesions • - FISH panel: Normal - Karyotype: Inversion 10 Reluctant to start therapy • RVD lite, with biochemical response (see kappa light chain levels) • - Difficulty tolerating therapy, painful shingles despite prophylaxis - Significant fatigue and “mental fog” on lenalidomide Discontinued RVD lite, initiated daratumumab (split dose)/dexamethasone • - Tolerating well - Plan to switch to subcutaneous daratumumab Questions: Given the fact that she had so much difficulty tolerating RVD lite, would I have been better off with the MAIA regimen for this woman? Any concerns about switching to subq daratumumab? Co-provided by

81-year-old frail woman Kappa light chain levels Co-provided by

63-year-old woman with PMH of systemic lupus, depression and back pain T8 and L1 compression fractures à Kyphoplasty for pain relief • ISS Stage II IgG kappa multiple myeloma (FISH: trisomy 9 and 11) • RVD + denosumab monthly • - Great response with normalization of light chains, resolution of M-spike after 4 cycles of RVD (see graphic) ASCT recommended • COVID-19 pandemic delays stem cell collection • One additional cycle of RVD administered • Currently, no clinical or biochemical evidence of myeloma (see PET CT) • Question: Given this lady’s lupus and significant history of depression, if she were found to be MRD-negative, would maintenance lenalidomide be preferred over consolidation autologous transplant? Co-provided by

63-year-old woman Normalization of light chains Co-provided by

63-year-old woman PET CT: No evidence of active disease Co-provided by

74-year-old woman ISS Stage II IgG lambda multiple myeloma • Lenalidomide/dexamethasone (good response) à Maintenance • lenalidomide - Deferred ASCT Relapse, large plasmacytoma in the jaw • 10/2017: Radiotherapy à Lenalidomide/ixazomib/dexamethasone à • Consolidation ASCT à Maintenance ixazomib Currently, remains on ixazomib with no evidence of relapse • - Worsening neuropathy causing ADL difficulties; B-12 not helpful Questions: How often is peripheral neuropathy seen with ixazomib, and how is • this managed? Would you dose reduce and discontinue if the peripheral neuropathy • does not improve? How long would you continue the ixazomib? • Co-provided by

74-year-old woman No M spike and Normal Light Chains Co-provided by

74-year-old woman Normal Creatinine and Calcium Co-provided by

74-year-old woman Stable CBC 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