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Meet The ProfessorManagement of Multiple Myeloma
Kenneth C Anderson, MDKraft Family Professor of Medicine
Harvard Medical SchoolDirector, Jerome Lipper Multiple Myeloma Center and
LeBow Institute for Myeloma TherapeuticsDana-Farber Cancer Institute
Boston, Massachusetts
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Commercial Support
This activity is supported by educational grants from Adaptive Biotechnologies Corporation, Celgene Corporation, GlaxoSmithKline, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, and Takeda Oncology.
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Potential Conflicts of Interest
USF Health endorses the standards of the ACCME that require everyone in a position to control the content of an accredited educational activity to disclose all financial relationships with commercial interests that are related to the content of the educational activity. All accredited activities must be balanced, independent of commercial bias, and promote improvements or quality in healthcare. All recommendations involving clinical medicine must be based on evidence accepted within the medical profession.
USF Health will identify, review, and resolve all conflicts of interest that speakers, authors, or planners disclose prior to an educational activity being delivered to learners. Disclosure of a relationship is not intended to suggest or condone bias in any presentation, but is made to provide participants with information that might be of potential importance to their evaluation of a presentation.
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Non-Faculty Disclosures
USF Health CPD Staff and Research To Practice CME Planning Committee Members, Staff, and Reviewers have no relevant conflicts to disclose.
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Accreditation
USF Health is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
USF Health designates this live activity for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
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AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) —MAINTENANCE OF CERTIFICATION (MOC)
Successful completion of this CME activity, which includes participation in the evaluation component and a short post-test, enables the participant to earn up to 1 Medical Knowledge MOC point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.
Please note, this program has been specifically designed for the following ABIM specialties: medical oncology and hematology.
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Dr Love — DisclosuresDr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following commercial interests: AbbVie Inc, AcertaPharma — A member of the AstraZeneca Group, Adaptive Biotechnologies Corporation, Agendia Inc, AgiosPharmaceuticals Inc, Amgen Inc, Array BioPharma Inc, a subsidiary of Pfizer Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Biodesix Inc, bioTheranostics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, Daiichi Sankyo Inc, Dendreon Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Epizyme Inc, ExelixisInc, Foundation Medicine, Genentech, a member of the Roche Group, Genmab, Genomic Health Inc, Gilead Sciences Inc, GlaxoSmithKline, Grail Inc, Guardant Health, Halozyme Inc, Helsinn Healthcare SA, ImmunoGenInc, Incyte Corporation, Infinity Pharmaceuticals Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Karyopharm Therapeutics, Kite, A Gilead Company, Lexicon Pharmaceuticals Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Merrimack Pharmaceuticals Inc, Myriad Genetic Laboratories Inc, Natera Inc, Novartis, Oncopeptides, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Prometheus Laboratories Inc, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Sandoz Inc, a Novartis Division, Sanofi Genzyme, SeagenInc, Sirtex Medical Ltd, Spectrum Pharmaceuticals Inc, Sumitomo Dainippon Pharma Oncology Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro, A GSK Company, Teva Oncology, Tokai Pharmaceuticals Inc and Verastem Inc.
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Dr Anderson — Disclosures
Advisory Committee Bristol-Myers Squibb Company, Gilead Sciences Inc, Janssen Biotech Inc, Sanofi Genzyme, Takeda Oncology
Consulting Agreements Amgen Inc, Pfizer Inc, Precision BioSciences, Sumitomo Dainippon Pharma Oncology Inc
Ownership Interest Scientific founder of C4 Therapeutics and OncoPep
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Robert Z Orlowski, MD, PhD — Disclosures
Advisory Committee
Amgen Inc, Bristol-Myers Squibb Company, Celgene Corporation, EcoR1 Capital LLC, FORMA Therapeutics, Genzyme Corporation, GlaxoSmithKline, Ionis Pharmaceuticals Inc, Janssen Biotech Inc, Juno Therapeutics, a Celgene Company, Kite, A Gilead Company, Legend Biotech, Molecular Partners, Regeneron Pharmaceuticals Inc, Sanofi Genzyme, Servier, Takeda Pharmaceuticals North America Inc
Consulting Agreement STATinMED
Contracted ResearchBioTheryX Inc, CARsgen Therapeutics, Celgene Corporation, ExelixisInc, Janssen Biotech Inc, Sanofi Genzyme, Takeda Pharmaceuticals North America Inc
Ownership Interest Asylia Therapeutics Inc (founder, patents, equity)
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You may submit questions using the Zoom Chat
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We Encourage Clinicians in Practice to Submit Questions
Feel free to submit questions now before the program begins and throughout the program.
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Familiarizing Yourself with the Zoom InterfaceHow to answer poll questions
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Upcoming Webinars
Meet The Professor: Management of Chronic Lymphocytic Leukemia
Friday, November 20, 202012:00 PM – 1:00 PM ET
ModeratorNeil Love, MD
FacultyProf John G Gribben, MD, DSc, FMedSci
Meet The Professor: Management of Ovarian Cancer
Monday, November 23, 202012:00 PM – 1:00 PM ET
ModeratorNeil Love, MD
FacultyDeborah K Armstrong, MD
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Upcoming Webinars
Year in Review: Clinical Investigators Provide Perspectives on the Most Relevant New Publications, Data Sets and Advances in OncologyProstate Cancer
Tuesday, December 1, 20205:00 PM – 6:00 PM ET
ModeratorNeil Love, MD
FacultyEmmanuel S Antonarakis, MDAndrew J Armstrong, MD, ScM
Consensus or Controversy? Investigators Discuss Clinical Practice Patterns and Available Research Data Guiding the Management of Hematologic Cancers
Friday, December 4, 2020
ModeratorNeil Love, MD
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Thank you for joining us!
CME and ABIM MOC credit information will be emailed to each participant within 5 business days.
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Meet The ProfessorManagement of Multiple Myeloma
Kenneth C Anderson, MDKraft Family Professor of Medicine
Harvard Medical SchoolDirector, Jerome Lipper Multiple Myeloma Center and
LeBow Institute for Myeloma TherapeuticsDana-Farber Cancer Institute
Boston, Massachusetts
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Meet The Professor Program Participating Faculty
Rafael Fonseca, MDGetz Family Professor of CancerDirector for Innovation and Transformational RelationshipsInterim Executive Director of the Mayo Clinic Comprehensive Cancer CenterChair, Department of Internal MedicineDistinguished Mayo InvestigatorMayo Clinic in ArizonaPhoenix, Arizona
Shaji K Kumar, MDMark and Judy Mullins Professor of Hematological MalignanciesConsultant, Division of HematologyProfessor of Medicine, Mayo ClinicRochester, Minnesota
Irene M Ghobrial, MDProfessor of MedicineDirector, Clinical Investigator Research ProgramDirector, Michele and Stephen Kirsch LaboratoryHarvard Medical SchoolDana-Farber Cancer InstituteBoston, Massachusetts
Jonathan L Kaufman, MDAssociate Professor of Hematology and Medical OncologyWinship Cancer Institute of Emory UniversityAtlanta, Georgia
Kenneth C Anderson, MDKraft Family Professor of MedicineHarvard Medical SchoolDirector, Jerome Lipper Multiple Myeloma Centerand LeBow Institute for Myeloma TherapeuticsDana-Farber Cancer InstituteBoston, Massachusetts
Sergio A Giralt, MDDeputy Division Head of Hematologic MalignanciesMelvin Berlin Family Chair in Myeloma ResearchMemorial Sloan Kettering Cancer Center Professor of Medicine, Weill Cornell Medical CollegeNew York, New York
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Robert Z Orlowski, MD, PhDFlorence Maude Thomas Cancer Research ProfessorDepartment of Lymphoma and MyelomaProfessor, Department of Experimental TherapeuticsDirector, Myeloma SectionDivision of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHouston, Texas
Nikhil C Munshi, MDKraft Family ChairDirector of Basic and Correlative ScienceJerome Lipper Multiple Myeloma CenterProfessor of MedicineHarvard Medical SchoolDana-Farber Cancer InstituteBoston, Massachusetts
Meet The Professor Program Participating Faculty
Sagar Lonial, MDChair and ProfessorDepartment of Hematology and Medical OncologyAnne and Bernard Gray Family Chair in CancerChief Medical OfficerWinship Cancer InstituteEmory University School of MedicineAtlanta, Georgia
Joseph Mikhael, MDProfessor, Applied Cancer Research and Drug DiscoveryTranslational Genomics Research InstituteCity of Hope Cancer CenterPhoenix, Arizona
Ola Landgren, MD, PhDProfessor of MedicineLeader, Experimental Therapeutics ProgramLeader, Myeloma ProgramSylvester Comprehensive Cancer CenterUniversity of MiamiMiami, Florida
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Noopur Raje, MD DirectorCenter for Multiple MyelomaMassachusetts General Hospital Cancer CenterProfessor of MedicineHarvard Medical SchoolBoston, Massachusetts
Project ChairNeil Love, MDResearch To PracticeMiami, Florida
Nina Shah, MDAssociate Professor of Medicine University of California, San FranciscoDivision of Hematology-OncologySan Francisco, California
Meet The Professor Program Participating Faculty
S Vincent Rajkumar, MDEdward W and Betty Knight ScrippsProfessor of MedicineMayo ClinicRochester, Minnesota
Krina K Patel, MD, MScAssociate ProfessorCenter Medical DirectorDepartment of Lymphoma/MyelomaDivision of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHouston, Texas
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We Encourage Clinicians in Practice to Submit Questions
You may submit questions using the Zoom Chat
option below
Feel free to submit questions now before the program begins and throughout the program.
-
Co-provided by
Familiarizing Yourself with the Zoom InterfaceHow to answer poll questions
When a poll question pops up, click your answer choice from the available options. Results will be shown after
everyone has answered.
-
Meet The ProfessorManagement of Chronic Lymphocytic Leukemia
Friday, November 20, 202012:00 PM – 1:00 PM ET
Prof John G Gribben, MD, DSc, FMedSci
ModeratorNeil Love, MD
Faculty
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Meet The ProfessorManagement of Ovarian Cancer
Monday, November 23, 202012:00 PM – 1:00 PM ET
Deborah K Armstrong, MD
ModeratorNeil Love, MD
Faculty
-
Year in Review: Clinical Investigators Provide Perspectives on the Most Relevant New Publications,
Data Sets and Advances in Oncology Prostate Cancer
Tuesday, December 1, 20205:00 PM – 6:00 PM ET
Emmanuel S Antonarakis, MDAndrew J Armstrong, MD, ScM
ModeratorNeil Love, MD
Faculty
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Consensus or Controversy? Investigators Discuss Clinical Practice Patterns and Available Research
Data Guiding the Management of Hematologic CancersA 4-Part Friday Satellite Symposia Live Webinar Series Preceding
the 62nd ASH Annual MeetingFriday, December 4, 2020
Multiple Myeloma8:30 AM – 10:00 AM Pacific Time(11:30 AM – 1:00 PM ET)
Chronic Lymphocytic Leukemia12:00 PM – 1:30 PM Pacific Time (3:00 PM – 4:30 PM ET)
Acute Myeloid Leukemia3:00 PM – 4:30 PM Pacific Time (6:00 PM – 7:30 PM ET)
Hodgkin and Non-Hodgkin Lymphoma7:00 PM – 8:30 PM Pacific Time (10:00 PM – 11:30 PM ET)
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Meet The ProfessorManagement of Multiple Myeloma
Kenneth C Anderson, MDKraft Family Professor of Medicine
Harvard Medical SchoolDirector, Jerome Lipper Multiple Myeloma Center and
LeBow Institute for Myeloma TherapeuticsDana-Farber Cancer Institute
Boston, Massachusetts
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Co-provided by
Robert Z Orlowski, MD, PhDDirector, Myeloma Section
Division of Cancer MedicineThe University of Texas
MD Anderson Cancer CenterHouston, Texas
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Meet The Professor with Dr Anderson
Module 1: Cases from Dr Orlowski
• An 82-year-old woman with newly diagnosed myeloma• A 47-year-old man with newly diagnosed high-risk myeloma; del(17p)• A 63-year-old man with t(11;14) disease and early relapse after ASCT• A 56-year-old man with multiple regimen-refractory myeloma• A 55-year-old woman with amyloid light chain amyloidosis• A 53-year-old woman with smoldering myeloma• Perspectives on the molecular classification of myeloma and identification of patients who will respond to
therapy
Module 2: Myeloma Journal Club with Dr Anderson
Module 3: Beyond the Guidelines — Clinical Investigator Approaches to Common Clinical Scenarios
Module 4: Key Papers and Recent Approvals
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Case Presentation – Dr Orlowski: An 82-year-old woman with newly diagnosed myeloma
• An 82-year-old woman presenting with foamy urine
• Laboratory: 3.5 g proteinuria on 24o collection, Hgb 8.6, SCr 1.2
• Radiology: No notable lytic bony lesions
• PET/CT: No areas of increased uptake
• Myeloma labs: 0.5 g/dL IgAl monoclonal protein + l light chains
• Staging: b2 microglobulin 2.6, albumin 2.5, LDH 345
• Bone marrow: 15% plasma cells, l restricted
• Molecular studies: FISH with del 13, no other abnormalities
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: An 82-year-old woman with newly diagnosed myeloma (continued)
Questions
• In a robust older patient, what is the best induction regimen?- RVd, RVd-lite, DRd?
• If the patient were frail, would that change your management?- Two versus three drugs?
• If the patient were curious about stopping therapy and got NGF-based MRD testing which was negative, would you stop treatment?
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 47-year-old man with newly diagnosed high-risk myeloma; del(17p)
• A 47-year-old man presenting with back and rib pain after some heavy lifting
• Radiology: T7 compression fracture, multiple lytic lesions
• Laboratory: Hgb 10.1, BUN 43, SCr 3.2
• PET/CT: Multiple areas of increased uptake, no cord compression
• Myeloma labs: 4.5 g/dL IgGk monoclonal protein
• Staging: b2 microglobulin 5.6, albumin 4, LDH 569
• Bone marrow: 65% plasma cells, k restricted
• Molecular studies: FISH with del 17p in 75% of CD138+ cells
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 47-year-old man with newly diagnosed high-risk myeloma; del(17p) (continued)
Questions
• What is standard induction for high-risk myeloma?
• Drug access aside, would you add daratumumab?
• Does ASCT add benefit to high-risk disease, and would you do single or tandem?
• Do you make treatment decisions based on the percentage involvement of plasma cells with a particular genetic abnormality (low-level vs high)?
• In the era of COVID-19, for a patient with high-risk disease would you be more comfortable administering induction, and then collecting and storing stem cells for transplantation at a future date?
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 63-year-old man with t(11;14) disease and early relapse after ASCT• A 63-year-old man presented with a clavicular mass• Radiology: Expansile clavicular lesion but otherwise negative• Pathology: FNA showed sheets of plasma cells• PET/CT: No other areas of increased uptake• Myeloma labs: 2.5 g/dL IgGk monoclonal protein• Staging: b2 microglobulin 2.6, albumin 4.2, LDH 112• Bone marrow: 26% plasma cells, k restricted • Molecular studies: FISH with t(11;14), no other abnormalities• Undergoes VRd induction à ASCT, and is in a VGPR afterwards • Starts on lenalidomide maintenance• Develops new bone pain within 9 months of starting len• Repeat marrow: 38% plasma cells• Molecular studies: t(11;14) remains in 77% of CD138+ cells
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 63-year-old man with t(11;14) disease and early relapse after ASCT (continued)
Questions
• What are the best options for early, aggressive relapses after ASCT?
• Does t(11;14) and/or high BCL2 expression confer an inferior outcome with ASCT?
• Would you use a venetoclax-based regimen (maybe with bortezomib) early in such a patient?
• Is there a role for early CAR T-cell therapies/bispecific antibodies in this setting?
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 56-year-old man with multiple regimen-refractory myeloma• A 56-year-old man presented with bone pain• Radiology: Several lytic bony lesions• PET/CT: Multiple areas of increased uptake• Myeloma labs: 2.3 g/dL IgGl monoclonal protein + l light chains• Staging: b2 microglobulin 4.2, albumin 3.2, LDH 101• Bone marrow: 23% plasma cells, l restricted • Molecular studies: FISH with no abnormalities• Undergoes VRd + panobinostat induction ⇒ tandem ASCT on BMT CTN STaMINA study • Starts on lenalidomide maintenance but achieves only a PR• Progression after 4 years treated with carfilzomib/pomalidomide/dex• Has multiple relapses over the next few years and receives a number of regimens, including
bortezomib/panobinostat/dex, daratumumab/pomalidomide/dex, carfilzomib/bendamustine/dex, and elotuzumab with lenalidomide/dex
• Enrolled on bb2121 study but cells expand sluggishly, he has no CRS after re-infusion, and stable disease is best response
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 56-year-old man with multiple regimen-refractory (continued)
Dr Robert OrlowskiQuestions
• Do you need to see cytokine release syndrome for CAR T cells to work?
• If there has been failure of a BCMA-targeted agent, is it possible to re-treat with a different BCMA-targeted strategy?
• If not, what is the next best option in such a patient?
• Are there any novel approaches with belantamab mafodotin that you think are promising?
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Case Presentation – Dr Orlowski: A 55-year-old woman with amyloid light chain (AL) amyloidosis
• A 55-year-old woman presenting with rash and skin bruising
• Laboratory: 5.5 g proteinuria on 24o collection, Hgb 11.2, SCr 0.8
• Renal biopsy: Congo red+ areas defined as l light chains by mass spec
• PET/CT: No lytic or sclerotic areas
• Myeloma labs: 0.3 g/dL IgGl monoclonal protein + l light chains
• Staging: FLC-diff 135 mg/dL, cTnT 0.236 ng/mL, and NT-ProBNP 2,300
• Bone marrow: 5% plasma cells, l restricted
• Molecular studies: FISH with t(11;14)
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 55-year-old woman with AL amyloidosis (continued)
Questions
• What is the best initial therapy for AL amyloidosis?- CyBorD verus VRd?
- Chemo + ASCT versus straight to ASCT?
• If the patient receives ASCT, do you administer maintenance?
• What are new and exciting drugs in AL amyloidosis?- Venetoclax
- Antibodies
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 53-year-old woman with smoldering myeloma
• A 53-year-old woman found to have high total protein
• Laboratory: Hgb 13.2, SCr 0.8, Ca 8.9
• PET/CT: No bony areas of increased uptake
• Myeloma labs: 2.1 g/dL IgG lambda monoclonal protein
• Staging: b microglobulin 2.6, albumin 4.4, LDH 132, lambda/kappa of 23.5
• Bone marrow: 25% plasma cells, lambda restricted
• Molecular studies: FISH shows 3 copies of 1q21 in 33% of plasma cells
Dr Robert Orlowski
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Case Presentation – Dr Orlowski: A 53-year-old woman with smoldering myeloma (continued)
Questions
• What is the best stratification system for smoldering myeloma?
• If this patient has high-risk smoldering myeloma, would you watch and wait?
• Other than enrollment on a trial, would you recommend treating this type of patient, and if so, with what?- Lenalidomide?- Lenalidomide + dexamethasone?- Lenalidomide + dexamethasone + anti-CD38?
Dr Robert Orlowski
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Perspectives on the molecular classification of myeloma and identification of patients who will respond to therapy
Dr Robert Orlowski
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Co-provided by
Meet The Professor with Dr AndersonModule 1: Cases from Dr OrlowskiModule 2: Myeloma Journal Club with Dr Anderson• Myeloma: Current and future therapies• ENDURANCE trial: Carfilzomib with lenalidomide/dexamethasone (dex) for newly diagnosed, transplant-ineligible
myeloma• Outcomes for patients with hematologic cancer and COVID-19 infection• Maintenance approaches in myeloma• Phase I/II trial of ixazomib with pomalidomide/dex, an all-oral regimen for relapsed/refractory (R/R) myeloma• Timing and landscape of mutational processes shaping myeloma evolution• ELOQUENT-2 trial: Final overall survival results with elotuzumab/lenalidomide/dex for R/R myeloma• FIRST trial: Subanalysis of continuous lenalidomide and low-dose dex in Canadian/US transplant-ineligible patients• BCMA-targeted and other novel immunotherapeutic approaches in myeloma • Novel prognostic scoring system for autologous HCT in myeloma; long-term follow-up of the IFM 2009 trial• Genomic signatures that identify patients with myeloma likely to experience superior outcomes• Mechanisms of resistance to bortezomib and to BCMA CAR T-cell therapy• Activation of multiple cell-killing pathways by isatuximab
Module 3: Beyond the Guidelines — Clinical Investigator Approaches to Common Clinical Scenarios
Module 4: Key Papers and Recent Approvals
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Overview of Different Anti-Multiple Myeloma Strategies
Gulla A, Anderson KC. Haematologica 2020;105(10):247015.
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Lancet Oncol 2020;21(10):1317-30.
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ENDURANCE (E1A11): Primary PFS Endpoint(Second Interim Analysis)
Kumar SK et al. Lancet Oncol 2020;21(10):1317-30.
Time since randomization (months)
• Median OS has not been reached in either group at median follow-up of 24 months; patients will continue on long-term follow-up for overall survival
KRd: 34.6 months (95% CI 28.8-37.8)VRd: 34.4 months (95% CI 30.1-NE)HR 1.04 (95% CI 0.83-1.31); p = 0.74
Prog
ress
ion-
free
surv
ival
(%)
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ENDURANCE (E1A11): Treatment-Emergent Adverse Events of Interest
Berdeja JG. ASCO 2020 Discussant.
Treatment completionVRD 43.3%, KRD 61.6%
Discontinuation for ToxVRD 17.3%, KRD 9.9%
4.8
16.1
12.6
4.6
0
2.5
0.21
53.4
24.4
45.4
23.6
8
0.8
P < 0.001P < 0.001
VRd (n = 527) KRd (n = 526)
Cardiac, pulmonary and renal Peripheral neuropathy*
* Grades 1-2 not required reporting
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ENDURANCE (E1A11): Treatment-Related AEs
Kumar S et al. ASCO 2020;Abstract LBA3.
Heme + Non-Heme Non-Heme
VRd (n = 527) KRd (n = 526)
* Grade 3 heme not required reporting
Step 1 treated patients – Hem and non-hem AEs
VRd(n = 527)
N (%)
KRd(n = 526)
N (%)Diff
KRd-VRdChi-sqp-value
Grade 3-5* 313 (59.4) 345 (65.6) 6.2 0.038
(95% CI) (55.1-63.6) (61.3-69.6)
Grade 4-5 61 (11.6) 70 (13.3) 1.7 0.394
(95% CI) (9.0-14.6) (10.5-16.5)
Step 1 treated patients – Non-hem AEs
VRd(n = 527)
N (%)
KRd(n = 526)
N (%)Diff
KRd-VRdChi-sqp-value
Grade 3-5 254 (48.3) 254 (48.3) 6.9 0.024
(95% CI) (37.1- 45.7) (44.0-52.6)
Grade 4-5 21 (4.0) 43 (8.2) 4.2 0.004
(95% CI) (2.5-6.1) (6.0-10.9)
47.852.3
11.4 12.0
0.2 1.3 0.2 1.3
37.440.1
3.86.8
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ENDURANCE (E1A11): Treatment-Related AEs (≥2%)
Kumar S et al. ASCO 2020;Abstract LBA3.
Peripheral neuropathy *
DyspneaHyperglycemia
FatigueRash
Lung infectionThromboembolic event
DiarrheaHypertensionHeart failure
Acute kidney injuryEdema limbs
Generalized muscle weaknessInsomnia
Hypotension
VRd (n = 527)
KRd (n = 526)
Grade ≥3
*
**
*
%
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Outcomes of Patients with Hematologic Malignancies and COVID-19 Infection: A Report from the ASH Research Collaborative Data Hub
Wood WA et al.ASH 2020;Abstract 215.
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Outcomes for 250 Patients with Blood Cancers in the ASH Research Collaborative COVID-19 Registry for Hematology
Wood WA et al. ASH 2020;Abstract 215.
• Patients with a physician-estimated hematologic cancer prognosis of
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Chari A et al. Blood 2020;[Online ahead of print].
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A Phase I/II Study of Twice Weekly Ixazomib plus Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma: Results from Phase I Dose Escalation Cohorts
Nadeem O et al.ASH 2020;Abstract 1398.
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Nat Commun 2020;11(1):1917.
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Single-Cell Expansion Model for Melphalan and Germinal Center-Related Mutational Signatures
Rustad EH et al. Nat Commun 2020;11(1):1917.
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J Clin Oncol 2020;38(21):2380-9.
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Cancer Med 2020;[Online ahead of print].
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Cancers (Basel) 2020;12(6):1473.
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Dhakal B et al. Br J Haematol 2020;[Online ahead of print].
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J Clin Oncol 2020;38(27):3107-18.
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Genome-Wide Mutational Signatures in Newly Diagnosed Myeloma
Samur MK et al. J Clin Oncol 2020;38(27):3107-18.
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Leukemia 2020;[Online ahead of print].
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Leukemia 2020;[Online ahead of print].
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Immunotargets Ther 2020;9:201-15.
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Blood 2020;136(20):2334-5.
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Early versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow-Up Analysis of the IFM 2009 Trial
Perrot A et al.ASH 2020;Abstract 143.
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Biallelic Loss of BCMA Triggers Resistance to Anti-BCMA CAR T Cell Therapy in Multiple Myeloma
Samur MK et al.ASH 2020;Abstract 721.
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Blood Cancer J 2020;10(11):110.
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Front Immunol 2020;11:1771.
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Meet The Professor with Dr AndersonModule 1: Cases from Dr OrlowskiModule 2: Myeloma Journal Club with Dr Anderson• Myeloma: Current and future therapies• ENDURANCE trial: Carfilzomib with lenalidomide/dexamethasone (dex) for newly diagnosed, transplant-ineligible
myeloma• Outcomes for patients with hematologic cancer and COVID-19 infection• Maintenance approaches in myeloma• Phase I/II trial of ixazomib with pomalidomide/dex, an all-oral regimen for relapsed/refractory (R/R) myeloma• Timing and landscape of mutational processes shaping myeloma evolution• ELOQUENT-2 trial: Final overall survival results with elotuzumab/lenalidomide/dex for R/R myeloma• FIRST trial: Subanalysis of continuous lenalidomide and low-dose dex in Canadian/US transplant-ineligible patients• BCMA-targeted and other novel immunotherapeutic approaches in myeloma • Novel prognostic scoring system for autologous HCT in myeloma; long-term follow-up of the IFM 2009 trial• Genomic signatures that identify patients with myeloma likely to experience superior outcomes• Mechanisms of resistance to bortezomib and to BCMA CAR T-cell therapy• Activation of multiple cell-killing pathways by isatuximab
Module 3: Beyond the Guidelines — Clinical Investigator Approaches to Common Clinical Scenarios
Module 4: Key Papers and Recent Approvals
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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/daratumumab6. Rd/daratumumab
7. VTd (bortezomib/thalidomide/dexamethasone) with daratumumab
8. RVD/daratumumab
9. KRd/daratumumab10. Other
-
Co-provided by
Currently, what is your usual pretransplant induction regimen for a 65-year-old patient with multiple myeloma (MM) and no high-risk features?
RVD
RVD/daratumumab
KRd
RVD
RVD/daratumumab
KRd
RVD
RVD
RVD
RVD
RVD
RVD
RVD
RVD/daratumumab
RVD
-
Co-provided by
Currently, what is your usual pretransplant induction regimen for a 65-year-old patient with del(17p) MM?
KRd
KRd
KRd
RVD/daratumumab
KRd
KRd/daratumumab
KRd
RVD/daratumumab
KRd
KRd
RVD/daratumumab
KRd
KRd/daratumumab
KRd/daratumumab
KRd
-
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 with normal renal function and no high-risk features?
Rd/dara
Rd/dara
Rd/dara
Rd/dara
Rd/dara
Rd/dara
RVD or RVD lite or Rd/dara
RVD or RVD lite
Rd or RVD or RVD lite or Rd/dara
Rd/dara
Rd
Rd/dara
RVD or RVD lite
Rd/dara
Rd/dara
Dara = daratumumab
-
Co-provided by
Regulatory and reimbursement issues aside, what is your preferred induction regimen for an 85-year-old patient with del(17p) MM?
RVD
RVD lite
RVD lite + dara
RVD lite
RVD lite
KRd
RVD lite
RVD lite
RVD lite
RVD lite
RVD lite
KRd
RVD/dara
RVD lite + dara
Rd/dara
-
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?
No
No
Yes – After combination therapy for decision of stem cell collection
and maintenance
Yes – Pts with high-risk disease
No
Yes – Pts in long-term CR or with plasmacytomas; monitoring amyloidosis
No
No
No
Yes, timing the number of induction cycles prior to stem cell collection
for patients in CR
Yes – Post-transplant, at CR, before and during maintenance
No
Yes — decision for transplant or not
Yes, post-transplant if ptin CR or VGPR
Yes, maintenance decision
-
Co-provided by
What is your usual recommendation for post-ASCT maintenance therapy for patients with MM and no high-risk features who received RVD induction therapy?
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide + dex
Lenalidomide
Lenalidomide
Lenalidomide
Lenalidomide
Dex = dexamethasone
-
Co-provided by
What is your usual recommendation for post-ASCT maintenance therapy for patients with del(17p) MM who received RVD induction therapy?
Lenalidomide + bortezomib
Len/bortez± dex
Lenalidomide
Len/bortez± dex
Len/bortez± dex
Len/ixa± dex
Len/K ± dex
Lenalidomide + bortezomib
Len/ixa± dex orLen/bortez± dex
Len/ixa± dex
Len/bortez± dex
Lenalidomide + bortezomib
Lenalidomide + bortezomib
Len/ixa± dex
Lenalidomide + bortezomib
Len = lenalidomide; ixa = ixazomib; dex = dexamethasone; bortez = bortezomib; K = carfilzomib
-
Co-provided by
What is your usual treatment recommendation for a patient with MM who receives RVD followed by ASCT and maintenance lenalidomide for 1.5 years who then experiences an asymptomatic biochemical relapse?
1. Carfilzomib +/- dexamethasone2. Pomalidomide +/- dexamethasone
3. Carfilzomib + pomalidomide +/- dexamethasone
4. Elotuzumab + lenalidomide +/- dexamethasone
5. Elotuzumab + pomalidomide +/- dexamethasone
6. Daratumumab + lenalidomide +/- dexamethasone7. Daratumumab + pomalidomide +/- dexamethasone
8. Daratumumab + bortezomib +/- dexamethasone
9. Ixazomib + Rd
10. Other
-
Co-provided by
What is your usual treatment recommendation for a patient with MM who receives RVD followed by ASCT and maintenance lenalidomide for 1.5 years who then experiences an asymptomatic biochemical relapse?
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/len + dex
Dara/pom ± dexCarfilzomib/pom ± dex if high risk
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom + dex
Dara/pom ± dex
Dara/carfilzomib + dex
Pom = pomalidomide
-
Co-provided by
What is your usual treatment recommendation for a patient with MM who receives RVD followed by ASCT and maintenance lenalidomide for 3 years who then experiences an asymptomatic biochemical relapse?
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/pom ± dex
Dara/len + dex
Pom ± dex OR Dara/pom ± dex
Ixazomib + Rd
Elo/pom ± dex
Dara/pom +/- dex OR Elo/pom +/- dex
Dara/pom + dex
Dara/pom ± dex
Dara/carfilzomib + dex
Elo = elotuzumab
-
Co-provided by
In general, when do you refer patients for possible inclusion in trials of BCMA-targeted CAR T-cell therapy?
Triple-class refractory, reasonable PS, especially high-risk pts
Few treatment options, slow relapse to wait the time to get cells
Per protocol eligibility criteria
Triple-class refractory
2-3 prior lines, good PS, counts OK
Refractory to all drugs
After failure of 3rd-line treatment
>3 prior regimens
As early as possible
Multiply R/R setting; more recently in earlier settings if trial available
Having received combo of PI, IMiD and anti-CD38 Ab and disease progressing
Refractory to an IMiD, PI and CD38 Ab; if high-risk then earlier per available trials
As early as possible in pts w/ high-risk cytogenetics
Penta-refractory (Len, pom, bort, dara and carfilzomib)
Beyond 2nd relapse
PI = proteasome inhibitor; IMiD = immunomodulatory drug
-
Co-provided by
Meet The Professor with Dr AndersonModule 1: Cases from Dr OrlowskiModule 2: Myeloma Journal Club with Dr Anderson• Myeloma: Current and future therapies• ENDURANCE trial: Carfilzomib with lenalidomide/dexamethasone (dex) for newly diagnosed, transplant-ineligible
myeloma• Outcomes for patients with hematologic cancer and COVID-19 infection• Maintenance approaches in myeloma• Phase I/II trial of ixazomib with pomalidomide/dex, an all-oral regimen for relapsed/refractory (R/R) myeloma• Timing and landscape of mutational processes shaping myeloma evolution• ELOQUENT-2 trial: Final overall survival results with elotuzumab/lenalidomide/dex for R/R myeloma• FIRST trial: Subanalysis of continuous lenalidomide and low-dose dex in Canadian/US transplant-ineligible patients• BCMA-targeted and other novel immunotherapeutic approaches in myeloma • Novel prognostic scoring system for autologous HCT in myeloma; long-term follow-up of the IFM 2009 trial• Genomic signatures that identify patients with myeloma likely to experience superior outcomes• Mechanisms of resistance to bortezomib and to BCMA CAR T-cell therapy• Activation of multiple cell-killing pathways by isatuximab
Module 3: Beyond the Guidelines — Clinical Investigator Approaches to Common Clinical Scenarios
Module 4: Key Papers and Recent Approvals
-
Co-provided by
Lancet Oncol 2020;21(10):1317-30
-
Co-provided by
ENDURANCE (E1A11): Primary PFS Endpoint(Second Interim Analysis)
Kumar SK et al. Lancet Oncol 2020;21(10):1317-30.
Time since randomization (months)
• Median OS has not been reached in either group at median follow-up of 24 months; patients will continue on long-term follow-up for overall survival
KRd: 34.6 months (95% CI 28.8-37.8)VRd: 34.4 months (95% CI 30.1-NE)HR 1.04 (95% CI 0.83-1.31); p = 0.74
Prog
ress
ion-
free
surv
ival
(%)
-
Co-provided by
ENDURANCE (E1A11): Treatment-Emergent Adverse Events of Interest
Berdeja JG. ASCO 2020 Discussant.
Treatment completionVRD 43.3%, KRD 61.6%
Discontinuation for ToxVRD 17.3%, KRD 9.9%
4.8
16.1
12.6
4.6
0
2.5
0.21
53.4
24.4
45.4
23.6
8
0.8
P < 0.001P < 0.001
VRd (n = 527) KRd (n = 526)
Cardiac, pulmonary and renal Peripheral neuropathy*
* Grades 1-2 not required reporting
-
Co-provided by
ENDURANCE (E1A11): Treatment-Related AEs
Kumar S et al. ASCO 2020;Abstract LBA3.
Heme + Non-Heme Non-Heme
VRd (n = 527) KRd (n = 526)
* Grade 3 heme not required reporting
Step 1 treated patients
VRd(n = 527)
KRd(n = 526)
Rates N (%) N (%)Diff
KRd-VRdChisq p-value
Grade 3-5 313 (59.4) 345 (65.6) 6.2 0.038
(95% CI) (55.1-63.6) (61.3-69.6)
Grades 4-5 61 (11.6) 70 (13.3) 1.7 0.394
(95% CI) (9.0-14.6) (10.5-16.5)
Step 1 treated patients
VRd(n = 527)
KRd(n = 526)
Rates N (%) N (%)Diff
KRd-VRdChisq p-value
Grade 3-5 254 (48.3) 254 (48.3) 6.9 0.024
(95% CI) (37.1- 45.7) (44.0-52.6)
Grades 4-5 21 (4.0) 43 (8.2) 4.2 0.004
(95% CI) (2.5-6.1) (6.0-10.9)
47.852.3
11.4 12.0
0.2 1.3 0.2 1.3
37.440.1
3.86.8
-
Co-provided by
ENDURANCE (E1A11): Treatment-Related AEs (≥2%)
Kumar S et al. ASCO 2020;Abstract LBA3.
Peripheral neuropathy *
DyspneaHyperglycemia
FatigueRash
Lung infectionThromboembolic event
DiarrheaHypertensionHeart failure
Acute kidney injuryEdema limbs
Generalized muscle weaknessInsomnia
Hypotension
VRd (n = 527)
KRd (n = 526)
≥ Grade 3
*
**
*
%
-
Co-provided by
N Engl J Med 2019;380(22):2104-15.
-
Co-provided byFacon T et al. N Engl J Med 2019;380(22):2104-15.
MAIA Primary Endpoint: Progression-Free SurvivalNDMM Transplant Ineligible
30 mo
Prog
ress
ion-
free
surv
ival
0
20
40
60
80
100
0 3 6 9 12 15 18 42
Months
2721 24 30
RdMedian: 31.9 mo
D-RdMedian: Not reached
33 36 39
HR: 0.56 p < 0.001
71%
56%
-
Co-provided by
MAIA: Overall Response Rate and MRD (NGS; 10-5 Sensitivity Threshold) Rate
Facon T et al. N Engl J Med 2019;380(22):2104-15.
1428
32
28
1712.5
30 12.5
0
10
20
30
40
50
60
70
80
90
100
D-Rd(n = 368)
Rd(n = 369)
ORR
, %
PR VGPR CR sCR
p < 0.001
ORR = 81%
ORR = 93%
≥CR:48%
≥VGPR:79%
≥CR:25%
≥VGPR:53%
24%
7%
0
5
10
15
20
25
30
D-Rd(n = 368)
Rd(n = 369)
MRD
-neg
ativ
e ra
te, %
p < 0.0013.4X
-
Co-provided by
GRIFFIN Randomized Phase II Study Design
Primary endpoint: Stringent CR by end of consolidation
Voorhees P et al. IMW 2019;Abstract 906.www.clinicaltrials.gov. Accessed January 23, 2020 (NCT02874742).
TR
ANSPL
ANT
D-RVd
RVd
Key Eligibility• Transplant-eligible
NDMM• 18-70 years old• ECOG 0-2
R 1:1 (N = 223)
D-RVd
RVd
D-R
R
21-day cycles 21-day cycles
InductionCycles 1-4
ConsolidationCycles 5-6
MaintenanceCycles 7-32
28-day cycles
-
Co-provided by
GRIFFIN Primary Endpoint: sCR at the End of Consolidation
Voorhees P et al. IMW 2019;Abstract 906.
42.4%32.0%
0
10
20
30
40
50
60
70
80
90
100
D-RVd(n = 99)
RVd(n = 97)
Patie
nts (
%)
sCR odds ratio: 1.57p = 0.068
8.118.6
39.430.9
9.1 10.3
42.4 32.0
0
10
20
30
40
50
60
70
80
90
100
D-RVd(n = 99)
RVd(n = 97)
ORR = 99.0%
PR VGPR CR sCR
ORR: p = 0.0160
ORR = 91.8%
Patie
nts (
%)
≥CR:51.5%
≥CR:42.3%
≥VGPR:73.2%≥VGPR:
90.9%
-
Co-provided by
GRIFFIN: Depth of Response Over Time
Voorhees P et al. IMW 2019;Abstract 906.
Clinicalcutoff
End ofconsolidation
End ofASCT
End ofinduction
Clinicalcutoff
End ofconsolidation
End ofASCT
End ofinduction
0
10
20
30
40
50
60
70
80
90
100Pa
tient
s (%
)
D-RVd RVd
2.0
26.3
52.5
7.1
12.1
1.012.1
59.6
6.1
21.2
1.08.1
39.4
9.1
42.4
1.07.1
29.3
13.1
49.5
8.2
35.1
43.3
6.27.2
8.2
25.8
46.4
5.2
14.4
8.2
18.6
30.9
10.3
32.0
8.2
17.5
26.8
10.3
37.1
PRSD/PD/NE VGPR CR sCR
≥CR:19.2% ≥CR:
27.3%≥CR:
51.5% ≥CR:62.6%
≥CR:13.4%
≥CR:19.6%
≥CR:42.3%
≥CR:47.4%
-
Co-provided by1. Kapoor P et al. J Clin Oncol 2013;31(36):4529-35. 2. Munshi NC et al. JAMA Oncol 2017:3(1):28-35.
PFS
(%)
OS
(%)
Median TTP for patients achieving CR1 PFS by MRD status2
sCR (n = 109): 50 months
CR (n = 37): 20 monthsnCR (n = 91): 19 months
sCR (n = 109): not reached
CR (n = 37): 81 months
Time since transplantation (years)
Time since transplantation (years)
Stringent Complete Response (sCR) and MRD as a Surrogate Endpoint for PFS and OS
MRD- mPFS: 54 months
MRD+ mPFS: 26 months
HR: 0.41p < 0.001
HR: 0.57p < 0.001
MRD- mOS: 98 months
MRD+ mOS: 82 months
nCR (n = 91): 60 months Cum
ulat
ive
Surv
ivin
g, %
PFS
(%)
Time (years)
Time (years)
MRD-(n = 660)
MRD+(n = 613)
MRD+(n = 501)
MRD-(n = 599)
Median OS for patients achieving CR1 OS by MRD status2
-
Co-provided by
Lancet 2019;393(10168):253-64.
-
Co-provided by
TOURMALINE-MM3 Primary Endpoint: Progression-Free Survival (ITT)
Dimopoulos MA et al. Lancet 2019;393(10168):253-64.
Ixazomib(n = 395)
Placebo(n = 261) HR p-value
Median PFS 26.5 mo 21.3 mo 0.72 0.0023
Months from randomisation
Prob
abili
ty o
f pro
gres
sion
-free
surv
ival
IxazomibPlacebo
-
Co-provided by
Relapsed/Refractory Myeloma
-
Co-provided by
First-in-Human Phase I Study of the Novel CELMoDAgent CC-92480 Combined with Dexamethasone (DEX) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM)
Richardson PG et al.ASCO 2020;Abstract 8500.
-
Co-provided by
CC-92480/Dexamethasone Combined with Bortezomib or Daratumumab or Carfilzomib
McCarthy P. ASCO 2020 Discussant
IMiD® Indication Clinical trials CELMoDs®
ThalidomideErythema NodosumErythema LeprosumMultiple Myeloma
LenalidomideMantle Cell LymphomaMultiple MyelomaMyelodysplasticSyndrome (5q-)
PomalidomideMultiple MyelomaKaposi Sarcoma
Abbreviation: CK1a: casein kinase 1a;CELMods: Cereblon E3 Ligase Modulation Drugs;CRL4: cullin-4 RING E3 ligase;CRBN: Cereblon; CNS: Central Nervous System;CUL4: Cullin-4; DDB1: DNA damage-binding protein 1;GSPT1: G1 To S Phase Transition 1;IKZF1: Ikaros zinc-finger protein 1;IKZF3: Aiolos zonc-finger protein 3;IMiDs: Immunomodulatory Drugs; MDS: Myelodysplastic Syndrome;Roc1: Ring finger protein;UB: UbiquitinationUBE2G1/2D3: Ubiquitin-conjugating enzymes
Multiple MyelomaDiffuse Large B-Cell LymphomaCNS LymphomaGlioblastomaHepatocellular CarcinomaChronic Lymphocytic Leukemia
Multiple MyelomaSystemic Lupus Erythematosus
Acute Myeloid Leukemia
Multiple Myeloma
Acute Myeloid Leukemia?(in vitro)
Holstein et al, Next-Generation Drugs. Targeting the Cereblon Ubiquitin Ligase. JCO 2018. Lu G et al eLife 2018Gandhi AK et al Br Haem 2014Krönke J et al Science 2014Hansen JD et al J Med Chem 2020Uehara, T et al Nat Chem Biol 2017
CC-122
CC-220
CC-90009
CC-92480Indisulam
CC-885
Lenalidomide
ThalidomideLenalidomidePomalidomideIberdomide(CC-220)CC-92480CC-885
CC-885CC-90009Avadomide(CC-122)
MDS del 5q Anti-TumorAnti-AML, -Lymphoma
Anti-Myeloma
Activity
-
Co-provided by
CC-92480/Dexamethasone Combined with Bortezomib or Daratumumab or Carfilzomib
McCarthy P. ASCO 2020 Discussant
• Future• NDMM and RRMM: Phase 1/2 of CC-92480 with
dexamethasone in combination with bortezomib ordaratumumab or carfilzomib NCT03989414
• Mitigating hematologic toxicity• Role in the context of lenalidomide, pomalidomide,
iberdomideOptimal combination therapyInduction, maintenance, salvage
Response
Resp
onse
, n (%
)
All evaluable(n = 76d)
10/14 days x 21.0 mg QD
(n = 10)MTD
21/28 days1.0 mg QD
(n = 11)RP2D
• At the RP2D 1.0 mg QD 21/28 days, 7 out of 11 patients were triple class-refractorye– 1 patient had CR, 1 VGPR, 2 PR, and 1 MR
Responses in patients with extramedullary plasmacytomas
a 1 patient in the 21/28 1.0 mg cohort had an unconfirmed VGPR as of the data cutoff date.b 1 patient in the 21/28 0.8 mg cohort had an unconfirmed PR as of the data cutoff date.c 1 patient in the 21/28 0.8 mg cohort had an unconfirmed PD as of the data cutoff date.CI = confidence interval; CR = complete response; EMP = extramedullary plasmacytomas; MR = minimal response; PD = progressivedisease; PET = positron emission tomography; PR = partial response; SD = stable disease; VGPR = very good partial response.
• Only patients on continuous schedules are shown PET scan Pre-treatment
PET scan post-C92480 C3D1
DLTS dose level
Dosing schedule Dose levelPatients,
n DLTs
10/14 days x 2
0.1 mg QD0.2 mg QD0.3 mg QD0.6 mg QD1.0 mg QD
3448
10
—1 patient (neutropenia)
—1 patient (pneumonitis)
2 patients (neutropenia; febrile neutropenia)
21/28 days 0.8 mg QD1.0 mg QD
1211
—3 patients (neutropenia; febrile neutropenia; sepsis)
3/14 days x 2
0.2 mg BID 4 —
0.4 mg BID 3 —
0.8 mg BID 4 —
7/14 days x 2
0.8 mg BID 3 —
1.6 mg QD 5 1 patient (febrile neutropenia)
2.0 mg QD 5 2 patients (pneumonitis; increased ALT, neutropenia, and thrombocytopenia)
• MTD was determined at 1.0 mg QD for both 10/14 days x 2 and 21/28 days schedules
Cont
inuo
usIn
tens
ive
DLTs by dose level
ALT, alanine transaminase; BID, twice daily; DLT, dose-limiting toxicity; MTD, maximum tolerated dose; QD, one daily.
-
Co-provided by
FDA Approves Carfilzomib and Daratumumab with Dexamethasone for Multiple MyelomaPress Release – August 20, 2020
“On August 20, 2020, the Food and Drug Administration approved carfilzomib and daratumumab in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
The efficacy of carfilzomib and daratumumab with dexamethasone was evaluated in two clinical trials, CANDOR and EQUULEUS.”
https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-carfilzomib-and-daratumumab-dexamethasone-multiple-myeloma
-
Weekly Selinexor, Bortezomib, and Dexamethasone (SVd) versus Twice Weekly Bortezomib and Dexamethasone (Vd) in Patients with Multiple Myeloma (MM) After One to Three Prior Therapies: Initial Results of the Phase III BOSTON Study
Dimopoulos MA et al.ASCO 2020;Abstract 8501.
-
Co-provided by
Time since randomization (months)
OPTIMISMM: Phase III Trial of Pomalidomide with Bortezomib and Dexamethasone in Relapsed/Refractory MM
Richardson PG et al. Lancet Oncol 2019;20(6):781-94.
Median PFS Pom-bort/dex Bort/dex HR (p-value)
Refractory to lenalidomide (n = 200; 191) 9.5 mo 5.6 mo 0.65 (0.0008)
Refractory to lenalidomide and 1 prior line of treatment (n = 64; 65) 17.8 mo 9.5 mo 0.55 (0.03)
All patients with 1-3 prior lines of therapy (including 2 or more cycles of lenalidomide)
Median 11.2 mo
Median 7.1 moPro
gres
sion
-free
surv
ival
(%) Pomalidomide, bortezomib and dexamethasone (n = 281)
Bortezomib and dexamethasone (n = 278)HR 0.61; two-sided p < 0.0001
-
Co-provided by
FDA Approval of Subcutaneous Daratumumab (Daratumumab and Hyaluronidase-fihj) for Newly Diagnosed or Relapsed/Refractory MMPress Release – May 1, 2020
“On May 1, 2020, the Food and Drug Administration approved daratumumab and hyaluronidase-fihj for adult patients with newly diagnosed or relapsed/refractory multiple myeloma. This new product allows for subcutaneous dosing of daratumumab.”
Daratumumab and hyaluronidase-fihj is approved for certain indications that intravenous daratumumab had previously received.
Efficacy of daratumumab and hyaluronidase-fihj (monotherapy) was evaluated in COLUMBA (NCT03277105), an open-label noninferiority trial randomly assigning 263 patients to daratumumab and hyaluronidase-fihj and 259 to intravenous daratumumab.
https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-daratumumab-and-hyaluronidase-fihj-multiple-myeloma
-
Co-provided by
COLUMBA: Phase III Noninferiority Trial of Subcutaneous (SC) versus Intravenous (IV) Daratumumab for Relapsed or Refractory MM
Mateos M-V et al. ASCO 2019;Abstract 8005.
Overall Response Rate
DARA IV (n = 258) DARA SC (n = 260) Odds ratio (p-value)Rate of infusion-related reactions 34.5% 12.7% 0.28 (
-
Co-provided by
Anti-CD38 Antibodies: Mechanism of Action, Structural and Pharmacologic Similarities and Differences
van de Donk NWCJ et al. Blood 2018;131(1):13-29.
Mechanism of action Daratumumab Isatuximab
Origin, isotype Human IgG-kappa Chimeric IgG1-kappa
CDC +++ +
ADCC ++ ++
ADCP +++ Not determined
PCD direct — ++
PCD cross linking +++ +++
Modulation ectoenzyme function + +++
Fc-dependent immune effector mechanisms and direct effects Immunomodulatory effectsDirect effectsAlteration in intracellular signalingCD38 enzymatic inhibition
Inhibition of adhesion
-
Co-provided by
FDA Approves New Therapy for Patients with Previously Treated Multiple MyelomaPress Release – March 02, 2020
“Today, the US Food and Drug Administration approved isatuximab-irfc, in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
The FDA approved isatuximab-irfc based on the results of a clinical trial involving 307 patients with relapsed and refractory multiple myeloma who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor.
Patients who received isatuximab-irfc in combination with pomalidomide and low-dose dexamethasone showed improvement in PFS with a 40% reduction in the risk of disease progression or death compared to patients who received pomalidomide and dexamethasone. These patients also had an overall response rate of 60.4%. In comparison, the patients who only received pomalidomide and low-dose dexamethasone had an overall response rate of 35.3%.”
https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-patients-previously-treated-multiple-myeloma
-
Co-provided by
FDA Granted Accelerated Approval to Belantamab Mafodotin-blmffor Multiple MyelomaPress Release – August 5, 2020
“The Food and Drug Administration granted accelerated approval to belantamab mafodotin-blmf for adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
Belantamab mafodotin-blmf was evaluated in DREAMM-2 (NCT 03525678), an open-label, multicenter trial. Patients received either belantamab mafodotin-blmf, 2.5 mg/kg or 3.4 mg/kg intravenously, once every 3 weeks until disease progression or unacceptable toxicity.
Efficacy was based on overall response rate (ORR) and response duration, as evaluated by an independent review committee using the International Myeloma Working Group uniform response criteria. The ORR was 31%. Seventy-three percent of responders had response durations ≥6 months. These results were observed in patients receiving the recommended dose of 2.5 mg/kg.
The prescribing information includes a Boxed Warning stating belantamab mafodotin-blmf causes changes in the corneal epithelium resulting in alterations in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes. Ophthalmic exams at baseline, prior to each dose, and promptly for worsening symptoms should be conducted.”
https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma
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Belantamab mafodotin2.5 mg/kg
(n = 97)
Belantamab mafodotin3.4 mg/kg
(n = 99)
Key eligibility•Relapsed or refractory MM•PD on at least 3 prior
therapies
•Refractory to IMiDs and proteasome inhibitors•Refractory and/or
intolerant to an anti-CD38 antibody
DREAMM-2 Randomized Phase II Study Design
R 1:1
Primary endpoint: Overall response in the intent-to-treat population as determined by an independent review committee
Lonial S et al. Lancet Oncol 2020;21(2):207-21.
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DREAMM-2: Response and Duration of Response
Time since first dose (days)
2.5 mg/kg 3.4 mg/kg
Overall response: 30 (31%)≥VGPR: 18 (19%)
Overall response: 34 (34%)≥VGPR: 20 (20%)
Time since first dose (days)
Patie
nts
Patie
nts
Lonial S et al. Lancet Oncol 2020;21(2):207-21.
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DREAMM-2: Select Adverse Events
Adverse events (AEs) of special interest, any grade
Belantamab mafodotin2.5 mg/kg
(n = 95)
Belantamabmafodotin3.4 mg/kg
(n = 99)
Thrombocytopenia 35% 59%
Infusion-related reactions 21% 16%
Corneal events 71% 75%
Drug-related serious AEs
Infusion-related reactions 3% 2%
Pyrexia 6% 5%
Sepsis 2% 2%
Pneumonia 4% 12%
Lonial S et al. Lancet Oncol 2020;21(2):207-21.
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DREAMM-6: Safety and Tolerability of Belantamab Mafodotin in Combination with Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma (RRMM)
Nooka AK et al.ASCO 2020;Abstract 8502.
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Novel Agents in Late-Stage Development
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Idecabtagene Vicleucel (ide-cel; bb2121), a BCMA-Targeted CAR T-Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Initial KarMMa Results
Munshi NC et al.ASCO 2020;Abstract 8503.
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Update of CARTITUDE-1: A Phase Ib/II Study of JNJ-4528, A B-cell Maturation Antigen (BCMA)-Directed CAR-T-Cell Therapy, in Relapsed/Refractory Multiple Myeloma
Berdeja JG et al.ASCO 2020;Abstract 8505.
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Orvacabtagene Autoleucel (orva-cel), a B-cell Maturation Antigen (BCMA)-Directed CAR T Cell Therapy for Patients (pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Update of the Phase 1/2 EVOLVE Study (NCT03430011)
Mailankody S et al.ASCO 2020;Abstract 8504.
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Co-provided byPatel K. ASCO 2020 Discussant
ASCO 2020: 3 BCMA CAR-T Studies
Characteristics SummaryKarMMa: idecabtagene
vicleucel(n = 128)
EVOLVE: orvacabtageneautoleucel
(n = 62)CARTITUDE-1: JNJ-4528
(n = 29)
Age 61 (33-78) 61 (33-77) 60 (50-75)
High risk cytogenetics, % 35 41* 27
Tumor burden in BM, % >50% PC = 51 — ≥60% PC = 24
Extramedullary PCs, % 39 23 10
Median prior line of therapy 6 (3-16) 6 (3-18) 5 (3-18)
Triple refractory, % 84 94 86
Bridging therapy, % 88 63 79
Unique properties Human BCMA,4-1BB, CD3z
Modified spacer,CD4: CD8 enriched
for CM
Median cell dose 0.72x106 cells/kg
2 BCMA single chain antibodies
* Included +1q21
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Co-provided byPatel K. ASCO 2020 Discussant
ASCO 2020: 3 BCMA CAR-T Studies
Safety Efficacy
KarMMa EVOLVE CARTITUDE-1
ANC ≥G3, % 89 90 100
plts ≥G3, % 52 47 69
CRS: all, ≥G3, % 84, 6 89, 3 93, 7
Med. time to CRS, duration, days
1 (1-12)5 (1-63)
2 (1-4)4 (1-10)
7 (2-12)4 (2-64)
ICANS: all, ≥G3, % 17, 3 13, 3 10, 3
HLH/MAS, % — 5 ? 7 (lfts)
Infections: all, ≥G3 % 69, — 40, 13 —, 19
Toci/steroid/anakinra use, % 52/15/0 76/52/23 79/21/21
KarMMa(n = 128)
EVOLVE(n = 62)
CARTITUDE-1(n = 29)
ORR, % 73 (66-81) 92 100
sCR/CR, % 33 36 86
MRD neg ≥10-5, %(of evaluable) 94 84 81
PFS, DoR,months 8.8/10.7 NR* NR**
Screened Apheresed Treated
150140128
—353529
? This was not listed at MAS/HLH, I am just speculating àcould this have been early MAS
* 300 x 106 cell dose cohort (lowest) = PFS 9.3 months, other med F/U = 8.8 and 2.3 month ** 9 mo PFS = 86%
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Co-provided byPatel K. ASCO 2020 Discussant
EVOLVE BCMA CAR-T StudyLook at that waterfall!
EVOLVE: Deep tumor burden reduction across dose levels
Max
imum
per
cent
age
decr
ease
300 x 106 CAR T cells 450 x 106 CAR T cells 600 x 106 CAR T cells
Serological responses* were observed in all patients treated at 450 x 106 and 600 x 108DLs
* Involved serum or urine parapretein, free light chains. ^ Patient with baseline extramedullary plasmacytoma.
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Meet The ProfessorManagement of Chronic Lymphocytic Leukemia
Friday, November 20, 202012:00 PM – 1:00 PM ET
Prof John G Gribben, MD, DSc, FMedSci
ModeratorNeil Love, MD
Faculty
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Thank you for joining us!
CME and ABIM MOC credit information will be emailed to each participant within 5 business days.