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Welcome participants at Gundersen Health System

Benjamin Parsons, DO

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Clinical Investigator Perspectives on the Current and Future Management of Multiple Myeloma

A Meet The Professor Series

Shaji K Kumar, MDMark and Judy Mullins Professor of Hematological Malignancies

Consultant, Division of HematologyProfessor of Medicine

Mayo ClinicRochester, Minnesota

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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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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, Boston Biomedical Inc, Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, Daiichi Sankyo Inc, Dendreon Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Exelixis Inc, 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, ImmunoGen Inc, Incyte Corporation, Infinity Pharmaceuticals Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, 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, Seattle Genetics, Sirtex Medical Ltd, Spectrum Pharmaceuticals Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro, A GSK Company, Teva Oncology, Tokai Pharmaceuticals Inc, ToleroPharmaceuticals and Verastem Inc.

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Dr Kumar — Disclosures

Advisory Committee AbbVie Inc, Celgene Corporation, Genentech, a member of the Roche Group, Janssen Biotech Inc, Takeda Oncology

Consulting Agreements

AbbVie Inc, Amgen Inc, Celgene Corporation, CellectarBiosciences Inc, GeneCentrix Inc, Genentech, a member of the Roche Group, Janssen Biotech Inc, Molecular Partners, Oncopeptides, Takeda Oncology

Contracted Research (to Institution)

AbbVie Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, CARsgen Therapeutics, Celgene Corporation, Genentech, a member of the Roche Group, Janssen Biotech Inc, Kite, A Gilead Company, Merck, Novartis, Takeda Oncology, TeneoBio

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Management of Multiple Myeloma (MM)Module 1: Clinical Decision-Making for Patients with Newly Diagnosed MM • Recent relevant data sets• Daratumumab-containing front-line therapy (CASSIOPEIA, MAIA, GRIFFIN)• Minimal residual disease (MRD) testing and use in treatment decision-making• Consolidation and maintenance therapy; emerging data with ixazomib

(TOURMALINE-MM3, TOURMALINE-MM4)

Module 2: Contemporary Management of Relapsed/Refractory MM• Recent relevant data sets• Data with daratumumab-containing regimens; split dosing• Combination regimens with ixazomib (TOURMALINE-MM1)• Recent FDA approval of selinexor and pivotal data from the STORM trial• Recent FDA approval of anti-CD38 isatuximab with pomalidomide/low-dose

dexamethasone and pivotal data from the ICARIA-MM study

Module 3: Novel Agents in Late-Stage Development• Recent relevant data sets• Belantamab mafodotin (DREAMM-2)• Clinical development of other anti-BCMA agents

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You may submit questions using the Zoom Chat

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Upcoming Live Webinars

Recent Advances in Medical Oncology: Immunotherapy and Other Nontargeted Approaches for Lung Cancer

Wednesday, August 5, 20205:00 PM – 6:30 PM ET

ModeratorNeil Love, MD

FacultyEdward B Garon, MD, MSStephen V Liu, MDDavid R Spigel, MD

Current Questions and Controversies in the Management of Lung Cancer

Thursday, August 6, 202012:00 PM – 1:00 PM ET


FacultyJohn V Heymach, MD, PhD

Upcoming Live Webinars

Virtual Molecular Tumor Board: Identification of New and Emerging Genomic Alterations in Metastatic Non-Small Cell Lung Cancer

Friday, August 7, 20209:00 AM – 10:00 AM ET


FacultyAlexander E Drilon, MDBryan P Schneider, MDMilan Radovich, PhD

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Thank you for joining us!

CME and MOC credit information will be emailed to each participant within 5 days.

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Welcome participants at Gundersen Health System

Benjamin Parsons, DO

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Meet The Professor Program Participating FacultyRafael 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

Ola Landgren, MD, PhDProfessor of MedicineChief, Myeloma ServiceDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New York

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

Shaji K Kumar, MDMark and Judy Mullins Professor of Hematological MalignanciesConsultant, Division of HematologyProfessor of MedicineMayo ClinicRochester, Minnesota

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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

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 CaliforniaSan FranciscoDivision of Hematology-OncologySan Francisco, California

Meet The Professor Program Participating Faculty

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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 commences and throughout the program.

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When a poll question pops up, click your answer choice from the available options. Results will be shown after

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Faculty

Recent Advances in Medical Oncology: Immunotherapy and Other Nontargeted

Approaches for Lung CancerWednesday, August 5, 2020

5:00 PM – 6:30 PM ET

Edward B Garon, MD, MSStephen V Liu, MD, PhD

David R Spigel, MD

Current Questions and Controversiesin the Management of Lung Cancer

Thursday, August 6, 202012:00 PM – 1:00 PM ET

FacultyJohn V Heymach, MD, PhD


Virtual Molecular Tumor Board: Optimizing Biomarker-Based Decision-Making for Patients with Solid Tumors

All sessions moderated by Neil Love, MD and featuring Bryan Schneider, MD and Milan Radovich, PhD of the Indiana University Health Precision Genomics Program

Identification of New and Emerging Genomic Alterations in Metastatic

Non-Small Cell Lung CancerFriday, August 7, 20209:00 AM – 10:00 AM ETAlexander E Drilon, MD

Recognition and Management of Targetable Tumor Mutations in Less

Common Cancer TypesFriday, August 14, 20209:00 AM – 10:00 AM ET

Marcia S Brose, MD, PhD

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Recent Advances in Medical Oncology: Multiple Myeloma

Faculty Shaji K Kumar, MDNoopur Raje, MD

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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

Currently, what pretransplant induction regimen would you recommend for a 65-year-old patient with multiple myeloma (MM)?

KRd

RVD

KRd

RVD/daratumumab

RVD

RVD

RVD

RVD

KRd/daratumumab

RVD/daratumumab

KRd

KRd

RVD/daratumumab

KRd

KRd

KRd

Standard risk Del(17p)

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Case Presentations

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Case 1 (Dr Parsons): Patient presenting with acute renal failure, and choice of post-transplant maintenance in 1q duplication high risk diseaseDiagnosis

1. Lambda Free Light Chain Multiple Myeloma, FISH panel 1q duplication, 1p deletion, and trisomy 9. High S phase proliferation 5.6%. High risk disease. iFLC 3,083 Lambda FLC, M-Spike 1.2. 80% lambda light chain restricted plasma cells on initial bone marrow biopsy

2. Myeloma induced renal impairment

Prior Therapy

1. CyBorD x 1 cycle started Sept 25th, 2019

2. Plasmapheresis started acutely Sept 24th, 2019

3. RVd chemotherapy x 5 cycles Oct 2019 - Feb 2020

4. Denosumab monthly initiated Oct 2019 - Jan 2020

67 y.o. male with a significant past medical history of HTN, HLD, and glaucoma who presented with acute AKI.

He reported a 2 month history of progressive weakness, multifocal pain, and progressive dyspnea. Upon presentation he complained of pain in the ribs, left shoulder blade, and right thigh. He had attempted conservative measures with NSAIDs and ice packs with no relief.

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Case 1 (cont)

Upon presentation to the ER, Creatinine 13.6, K 6, and Bicarb of 11. WBC normal, Hbg 11.5, and Plt 183. Patient started urgent dialysis. SPEP, IFE, and FLCs were ordered. His serum Lambda free light chains returned at 3,083 mg/dL. Hematology was consulted, and bone marrow biopsy was performed: 80% lambda light chain restricted malignant plasma cells consistent with active MM. Skeletal survey without focal lytic lesions, but significant for generalized osteopenia. SPEP returned with a 1.2 g/dL M-Spike, and IFE showed only a monoclonal free lambda light chain.

Patient underwent plasmapheresis with albumin replacement, 1 plasma volume, daily x 5 days. Patient was maintained on dialysis and had his dialyzer changed to an Ultrafiltration coefficient (mL/hr/mmHg) of 52 with good tolerance. Patient was started on CyBorD chemotherapy regimen with dexamethasone 40 mg day 1, 4, 8, and 11 and both cyclophosphamide 300 mg/m2 day 1, 8, and 15 + bortezomib 1.3 mg/m2 day 1, 4, 8, and 11 of a 21 day cycle. Prophylactic meds: acyclovir 400 mg BID, sulfamethoxazole/trimethoprim SS every MWF. Bone modifying therapy with denosumab SQ monthly was started due to severe renal dysfunction.

Completed cycle 1 of CyBorD. Work up returned FISH panel 1q duplication, 1p deletion, and trisomy 9. High S phase proliferation 5.6%. High risk disease. His post-cycle 1 Lambda free light chain dropped to 124.

He transitioned to RVd chemotherapy for cycle 2 with renally dose reduced Lenalidomide on dialysis. His post-cycle 2 Lambda free light chain had completely normalized.

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Case 1 (cont)

Over the course of the next 2-3 months he had slow renal recovery and was ultimately able to come off dialysis.

He completed 6 total cycles of induction therapy and achieved sCR by IMWG criteria with bone marrow biopsy showing 1% plasma cells and MRD negative by Flow cytometry. He tolerated induction well with only mild grade 1 IMiD rash, and no neuropathy to date.

He was taken for ASCT with high dose Melphalan and is now day 30 post transplant and recovering well.

Post-transplant maintenance — he is considering Dara SQ + Len vs Len on trial vs proteasome inhibitor maintenance seeing us at day 100 to decide post-transplant maintenance.

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Case 2 (Dr Parsons): Delayed stem cell transplant and maintenance in lenalidomide refractory patientDiagnosis

Kappa free light chain only Multiple Myeloma, R-ISS II, ISS III, karyotype with hyperdiploid, and no adverse cytogenetics. 70-80% plasma cells on bone marrow. iFree kappa 1325, iFree Lambda 0.82, iF K/L 1616. Diagnosed July 2016. Post induction achieved IMWG sCR

Prior Therapy

1. KRd x 9 cycles on E1A11 — started 8/2/16 - 4/11/17

2. Stem cell collection at UW Madison Dec 2016 — Delayed ASCT planned

3. Zoledronic acid 4 mg Q3 months — Discontinued August 2018 after 2 years of therapy

4. Lenalidomide 10 mg d1-21 of each 28 day cycle — indefinite maintenance on E1A11 started May 2017 - Feb 2020 due to progression of disease with documented bone marrow recurrence of clonal plasma cells in rising free light chain

5. Re-started Lenalidomide 25 mg daily x 21 days of a 28 day cycle with Dex 20 mg weekly in March 2020 —changed therapy due to minimal response

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Case 2 (cont)

Current Therapy

1. Elotuzumab, lenalidomide, and dexamethasone started June 2020. Dose of dexamethasone reduced due to side effects.

A now 64 y.o. male who presented to my practice in July 2016 at age 60 with elevated free kappa light chain, back pain, and weight loss.

He was found to have lumbar compression fractures at T12, L1, L2 and L3.

He underwent work up including CBC showing WBC 6.28, Hbg 11.2, Plt 363, SPEP M-Spike 0.3 g/dL with IFE showing a monoclonal free kappa light chain. His serum FLCs came back showing free kappa light chain of 1186.43 with a K/L ratio of 1464.73. Repeat free kappa light chain prior to cycle 1: 1325.58.

Bone marrow biopsy was performed which showed 70-80% plasma cells. Karyotype was hyperdiploid, and no adverse cytogenetics.

Final diagnosis Kappa free light chain Multiple Myeloma, R-ISS II, ISS III, karyotype with hyperdiploid, and no adverse cytogenetics. Lytic bone disease present, and 70-80% plasma cells on bone marrow. iFree kappa 1325, iFree Lambda 0.82, iF K/L 1616. Diagnosed July 2016.

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Case 2 (cont)

He was enrolled on E1A11 and randomized to KRd. He had stem cells collected after 2 cycles of therapy. He did develop a lower extremity DVT despite aspirin prophylaxis and was started on apixaban. He ultimately received 9 cycles of KRd induction, and largely tolerated well without significant cardiopulmonary toxicity. He had an excellent clinical response to therapy meeting IMWG criteria for sCR.Induction was followed by lenalidomide maintenance and he was randomized to indefinite maintenance. He received supportive care with bisphosphonates and completed 2 yrs of zoledronic acid Q 3 months.

At approximately 46 months from diagnosis he had progression of disease with rising kappa free light chains which prompted bone marrow biopsy subsequently revealing recurrence of kappa restricted clonal plasma cells, but only 3-5% of marrow. PET/CT showed no FDG avid lytic bone lesions. His calcium and renal function remained normal and he had no cytopenias.

His initial plan was for ASCT at first progression, but his transplant timing was delayed further due to COVID-19.

Instead his Lenalidomide was increased to 25 mg days 1-21 of a 28 day cycle and dexamethasone weekly was added, but he failed to have significant improvement in his free light chains after 2 months. We therefore added elotuzumab to his treatment regimen. He is tolerating this well.

He is now moving forward with ASCT at first progression. Will need plan for maintenance post delayed ASCT in a lenalidomide refractory patient.

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Recent Relevant Data Sets

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Carfilzomib, Lenalidomide, and Dexamethasone (KRd) versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) for Initial Therapy of Newly Diagnosed Multiple Myeloma (NDMM): Results of ENDURANCE (E1A11) Phase III Trial

Kumar S et al.ASCO 2020;Abstract LBA3. (Plenary)

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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

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): TEAEs 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 (≥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

Primary Analysis of the Randomized Phase II Trial of Bortezomib, Lenalidomide, Dexamthasone with/without Elotuzumab for Newly Diagnosed, High-Risk Multiple Myeloma (SWOG-1211)

Usmani SZ et al.ASCO 2020;Abstract 8507.

Co-provided by

Depth of Response to Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone (Isa-KRd) in Front-Line Treatment of High-Risk Multiple Myeloma: Interim Analysis of the GMMG-CONCEPT Trial

Weisel K et al.ASCO 2020;Abstract 8508.

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Other Key Data Sets

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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%

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?

Rd/dara

Rd/dara

Rd/dara

Rd/dara

Rd

Rd/dara

Rd or RVD or RVD lite or Rd/dara

RVD or RVD lite or Rd/dara

KRd

RVD lite

RVD lite + dara

RVD lite

RVD lite

RVD lite

RVD lite

RVD lite

Standard risk, normal renal function Del(17p)

Dara = daratumumab

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

Are there situations in which you believe community-based oncologists/hematologists should be ordering minimal residual disease (MRD) assessment to guide treatment decision-making for patients with MM?

Yes – Pts in long-term CR or with plasmacytomas; monitoring amyloidosis

Yes – Pts with high-risk disease

Yes – After combination therapy; if MRD-negative, collect and store stem cells. Then go straight to maintenance

No

Yes – Post-transplant, at CR, before and during maintenance

Yes, timing the number of induction cycles prior to stem cell collection for patients in CR

No

No, I don’t believe this test should be ordered in the community to make clinical decisions

Co-provided 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

What is your usual recommendation for post-ASCT maintenance therapy for patients with MM who received RVD induction therapy?

Lenalidomide

Lenalidomide

Lenalidomide

Lenalidomide

Lenalidomide + dex

Lenalidomide

Lenalidomide

Lenalidomide

Len/ixa± dex

Len/bortez± dex

Lenalidomide

Len/bortez± dex

Len/bortez± dex

Len/ixa± dex

Len/ixa± dex or Len/bortez± dex

Len/K ± dex

Standard-risk Del(17p)

Len = lenalidomide; ixa = ixazomib; dex = dexamethasone; bortez = bortezomib; K = carfilzomib

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






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

What is your usual treatment recommendation for a patient with MM who receives RVD followed by ASCT, who experiences asymptomatic biochemical relapse after …

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dexCarfilzomib/pom ± dex if high risk

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Dara/pom ± dex

Elo/pom ± dex

Ixazomib + Rd

Pom ± dex or dara/pom ± dex

Dara/pom ± dex

1.5 years of maintenance lenalidomide 3 years of maintenance lenalidomide

Dara = daratumumab; pom = pomalidomide;Elo = elotuzumab

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Case Presentations

Co-provided by

Case 3 (Dr Parsons)

Diagnosis

1. IgG/Kappa Multiple Myeloma, DS stage II, ISS 3, iFLC kappa 134, lambda 1.37, K/L 98.19, M-Spike 3.0, bone marrow with 50% plasma cells, karyotype 46XY, Myeloma FISH panel positive for deletion TP53 — high risk, diagnosed Aug 2016

2. Anemia, macrocytic

3. Thrombocytopenia

Previous Therapy

1. Six cycles RVd lite — 35 day cycle Aug 2016 - March 2017

2. Zoledronic acid

3. Maintenance lenalidomide

4. Bortezomib and dexamethasone 20 mg weekly started in July 2018 - Sept 2019

Current Therapy

Daratumumab, pomalidomide, dexamethasone

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Case 3 (cont)

Presented to my practice at 88 yrs old in Aug 2016 and we diagnosed him with IgG/Kappa Multiple Myeloma, DS stage II, ISS 3, iFLC kappa 134, lambda 1.37, K/L 98.19, M-Spike 3.0, bone marrow with 50% plasma cells, karyotype 46XY, Myeloma FISH panel positive for deletion TP53 — high risk.

He is a retired farmer who has a PMH significant for osteoarthritis, T2DM, acid reflux, and a history of kidney stones.

His oncologic history began with a decline in his overall health and increasing back pain. He began having difficulty performing his normal chores of milking and carrying feed around. He saw his PCP and labs were done including a CBC, which identified new macrocytic anemia, prompting further lab assessment including B12, iron studies, peripheral smear, retic count, sed rate, CRP, and haptoglobin. Sed rate was quite elevated at 108. Patient also had a new thrombocytopenia with platelet count 133,000. Iron studies, B12, and folate were unremarkable. Haptoglobin was elevated at 245. Creatinine was elevated at 1.34. Patient was referred to hematology for evaluation of his anemia. XR of the lumbar spine was ordered and identified compression fractures of T12, L2, L3 and L5. A bone marrow biopsy was performed showing multiple myeloma with approximately 50% clonal plasma cell involving the bone marrow. FISH panel positive for deletion TP53 — high risk.

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Case 3 (cont)

He was started on RVd lite 35 day cycle. Supportive care with zoledronic acid was initiated.

He received 6 cycles RVd lite, which he tolerated very well. He obtained a VGPR. He was transitioned to lenalidomide maintenance. At approximately 24 months from diagnosis he had biochemical progression of disease with rising M-Spike and kappa FLC. He wanted to minimize treatment and opted for bortezomib/dexamethasone alone. Had progression after around 14 months of therapy with worsening cytopenias with Plt 70-80K and rising M-Spike FLC. Stable renal function and no new bony issues.

He was transitioned to DPd. He is tolerating DPd well. He is now age 92 yrs and has moved into a NH.

However, due to COVID-19 now his NH states that if he continues to come for daratumumab he will need to be in indefinite isolation to protect the other NH residents.

We have discussed changing him to an all oral regimen? IPd?

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Case 4 (Dr Parsons): Relapsed/Refractory MM t11:14: Should you rechallengewith venetoclax, and role for prophylactic pinning of at-risk long boneDiagnosis

1. IgA/Lambda Multiple Myeloma, originally diagnosed in March 2008. Most recent progression March 2020. Last bone marrow biopsy 70% plasma cells, karyotype 46XX, Myeloma FISH panel 1q duplication, trisomy 9, monosomy 13, and CCND1/IGH fusion; t(11;14)

Prior Therapy

1. Radiation therapy to C2 plasmacytoma consisting of 4000 cGy in 20 fractions, completed on July 16, 2008

2. Lenalidomide/dexamethasone: status post 6 cycles completed August 2008. Best response was partial remission. Treatment discontinued due to disease progression

3. Bortezomib with dexamethasone: status post 6 cycles completed November 2008. Best response was partial remission. Treatment discontinued due to disease progression

4. Bortezomib/cyclophosphamide/dexamethasone: status post 3 cycles completed February 2009. Best response was stable disease. Treatment discontinued due to patient preference

5. Stem cell harvest Feb 2009, UW-Madison (patient has declined to pursue HDCT/SCT)

6. Pomalidomide and dexamethasone: Aug 2014 - Sept 2015

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Case 4 (cont)

7. Clinical trial — A Phase 3, Multicenter, Randomized, Double Blind Study of Bortezomib and Dexamethasone in Combination With Either Venetoclax or Placebo in Subjects With Relapsed or Refractory Multiple Myeloma Who Are Sensitive or Naïve to Proteasome Inhibitors. ABT199 (venetoclax) 1200 mg PO daily. Oct 2015 - April 2017 through Mayo Clinic in Scottsdale, AZ. Therapy stopped due to completion of trial — was responding to treatment at time of trial discontinuation

8. Ixazomib/lenalidomide/dexamethasone started Oct 2017. Discontinued July 2019 due to disease progression

9. Prophylactic pinning of the right humerus 1/24/2020

10. XRT to right humerus and scapula. 2000 cGy delivered in 5 fractions. 3/11/2020 - 3/17/2020.

Jan 2020 complained of right upper arm pain. Plain film X-ray obtained showing 4.2 cm lytic lesion in the right humerus.

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Case 4 (cont)

Mirel criteria calculated:

Upper limb+1Lower limb+2Trochanteric region+3

Size of lesionLess than 1/3 of bone diameter+11/3 to 2/3 of bone diameter+2More than 2/3 of bone diameter+3

Currently responding with DPd. She continues to refuse transplant. At progression selinexor based regimen, rechallenge with venetoclax, or other?

Nature of lesionBlastic+1Mixed+2Lytic+3

PainMild+1Moderate+2Functional+39 pointsProphylactic fixation indicated>33 %Risk of fracture at 6 months post-irradiation

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

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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.

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.

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Other Key Data Sets

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 moProg

ress

ion-

free

surv

ival

(%) Pomalidomide, bortezomib and dexamethasone (n = 281)

Bortezomib and dexamethasone (n = 278)HR 0.61; two-sided p < 0.0001

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Daratumumab-Based Regimens for Relapsed and/or Refractory MM

1 Dimopoulos MA et al. Haematologica 2018;103(12):2088-96; 2 Spencer A et al. Haematologica 2018;103(12):2079-87.

POLLUX1

Dara-Rd vs RdCASTOR2

Dara-Vd vs Vd

Prior therapies Bortezomib: 84% Len/Thal: 18%/43%

IMiD + PI: 44%

Bortezomib: 65%Len/Thal: 42%/49%

IMiD + PI: 48%

Median lines prior Tx 1 (range: 1-11) 2 (range: 1-10)

Median PFS (mo) – ITT (n = 569; 498)

NR vs 17.5HR 0.41, p < 0.0001

16.7 vs 7.1HR 0.31, p < 0.0001

Median PFS (mo) – prior Bort(n = 479; 326)

NR vs 17.5HR 0.40, p < 0.0001

12.1 vs 6.7HR 0.35

Median PFS (mo) – prior Len(n = 100; 209)

NR vs 18.6HR 0.32, p = 0.0008

9.5 vs 6.1HR 0.38

NR = not reached

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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

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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 (<0.0001)

DARA IV(n = 259)

ORR

, %

DARA SC(n = 263)

≥CR:2.7%

≥VGPR:17.0%

≥VGPR:19.0%

≥CR:1.9%

ORR = 37.1%ORR = 41.1%

Relative risk: 1.11P < 0.0001

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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

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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

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In general, when do you refer patients for possible inclusion in trials of BCMA-targeted CAR T-cell therapy?

Refractory to all drugs

Triple-class refractory

Per protocol eligibility criteria

Few treatment options, slow relapse to wait the time to get cells

Having received PI, IMiD and anti-CD38 antibody in combination and disease progressing

Multiply relapsed/refractory setting; more recently in earlier settings based on trial availability

As early as possible

After failure of 3rd-line treatment

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Glomeruli with increased volume, lobulated aspect, endocapillary hypercellularity with reduced capillary lumen and increased mesangial matrix

Da Fonseca GS et al. Hem Transfus Cell Ther 2018;40(1):86-89.

(D) Masson trichrome–magnification:20×

A B

C D

(A)Hematoxylin eosin (B)

Sirius red

(C) Periodic acid silver methenamine stain (PAMS)

Co-provided by

Glomeruli with increased volume, lobulated aspect, endocapillary hypercellularity with reduced capillary lumen and increased mesangial matrix

Da Fonseca GS et al. Hem Transfus Cell Ther 2018;40(1):86-89.

E F

G H

(E) Immunofluorescence for immunoglobulin G showing accentuated deposition in capillary loops, subendothelial glomerulus

(F and G)Enlargement of subendothelial space with randomly distributed fibrils and mesangial interposition (transmission electron microscopy: F–7000×; G–12,000×)

(H)Detail of the deposit of fibrillary material (transmission electron microscopy: 30,000×)

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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.

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.


Idecabtagene Vicleucel BCMA CAR T Study

PFS by Target Dose

• PFS increased by depth of response; median PFS was 20 mo in patients with CR/sCR

PFS by Best Response

• PFS increased with higher target dose; median PFS was 12 mo at 450 × 106 CAR+ T cells

CR/sCR 42 42 42 40 39 37 26 16 11 8 4 0VGPR 25 25 22 20 16 14 8 3 2 0 0

PR 27 16 10 9 5 1 0 0 0 0 0Nonresponders 34 8 83 70 64 56 35 19 13 8 4 0

0

0.2

0.4

0.6

0.8

1

0 2 4 6 8 10 12 14 16 18 20 22

Time, months

1.0

Median (95% CI), moCR/sCR: 20.2 (12.3−NE)VGPR: 11.3 (6.1−12.2)PR: 5.4 (3.8−8.2)Nonresponders: 1.8 (1.2−1.9)

0

0.2

0.4

0.6

0.8

1

0 2 4 6 8 10 12 14 16 18 20 22

PFS

Prob

abili

ty

Time, months

1.0

Median (95% CI), mo150 × 106 2.8 (1.0−NE)300 × 106 5.8 (4.2−8.9)450 × 106 12.1 (8.8−12.3)

Progression-free survival with single-cell infusion!

At risk, N150 × 106 4 2 1 1 1 1 1 1 1 1 1 0300 × 106 70 56 42 33 29 24 17 14 11 7 2 0450 × 106 54 44 40 36 34 31 17 4 1 0 0

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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.

Co-provided by

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.

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

Belantamabmafodotin2.5 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%



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Approaches for Lung CancerWednesday, August 5, 2020

5:00 PM – 6:30 PM ET

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David R Spigel, MD

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