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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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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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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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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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We Encourage Clinicians in Practice to Submit 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


FacultyDeborah K Armstrong, MD

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


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


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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 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


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


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.

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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


Prof John G Gribben, MD, DSc, FMedSci


Faculty

Meet The ProfessorManagement of Ovarian Cancer

Monday, November 23, 202012:00 PM – 1:00 PM ET

Deborah K Armstrong, 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


Faculty

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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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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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



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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%)


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

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.

Co-provided by

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

Co-provided by

Chari A et al. Blood 2020;[Online ahead of print].

Co-provided by

Co-provided by

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.

Co-provided by

Nat Commun 2020;11(1):1917.

Co-provided by

Single-Cell Expansion Model for Melphalan and Germinal Center-Related Mutational Signatures

Rustad EH et al. Nat Commun 2020;11(1):1917.

Co-provided by

J Clin Oncol 2020;38(21):2380-9.

Co-provided by

Co-provided by

Cancer Med 2020;[Online ahead of print].

Co-provided by

Cancers (Basel) 2020;12(6):1473.

Co-provided by

Dhakal B et al. Br J Haematol 2020;[Online ahead of print].

Co-provided by

J Clin Oncol 2020;38(27):3107-18.

Co-provided by

Genome-Wide Mutational Signatures in Newly Diagnosed Myeloma

Samur MK et al. J Clin Oncol 2020;38(27):3107-18.

Co-provided by

Leukemia 2020;[Online ahead of print].

Co-provided by

Immunotargets Ther 2020;9:201-15.

Co-provided by

Blood 2020;136(20):2334-5.

Co-provided by

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.

Co-provided by

Biallelic Loss of BCMA Triggers Resistance to Anti-BCMA CAR T Cell Therapy in Multiple Myeloma

Samur MK et al.ASH 2020;Abstract 721.

Co-provided by

Blood Cancer J 2020;10(11):110.

Co-provided by

Front Immunol 2020;11:1771.

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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

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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

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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

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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

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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

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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

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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


Len/ixa± dex orLen/bortez± dex

Len/ixa± dex

Len/bortez± dex



Len/ixa± dex


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





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.


• 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


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%)


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


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

Co-provided by

Belantamab mafodotin2.5 mg/kg

(n = 97)


(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.

Co-provided by

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


Co-provided by

DREAMM-2: Select Adverse Events

Adverse events (AEs) of special interest, any grade


(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%


Co-provided by

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.

Co-provided by

Novel Agents in Late-Stage Development

Co-provided by

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.

Co-provided by

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.

Co-provided by

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.

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


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%


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.

Meet The ProfessorManagement of Chronic Lymphocytic Leukemia


Prof John G Gribben, MD, DSc, FMedSci


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