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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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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.
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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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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
ModeratorNeil Love, MD
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
ModeratorNeil Love, MD
FacultyAlexander E Drilon, MDBryan P Schneider, MDMilan Radovich, PhD
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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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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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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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option below
Feel free to submit questions now before the program commences 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.
ModeratorNeil Love, MD
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
ModeratorNeil Love, MD
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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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
Recent Advances in Medical Oncology: Multiple Myeloma
Faculty Shaji K Kumar, MDNoopur Raje, MD
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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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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
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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
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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
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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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
Recent Relevant Data Sets
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.
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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.
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
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
Co-provided by
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
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×)
Co-provided by
Recent Relevant Data Sets
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
Co-provided byPatel K. ASCO 2020 Discussant
ASCO 2020: 3 BCMA CAR T Studies
Safety Efficacy
KarMMa EVOLVE CARTITUDE-1
ANC ≥G3, % 89 90 100
plts ≥G3, % 52 47 69
CRS: all, ≥G3, % 84, 6 89, 3 93, 7
Med. time to CRS, duration, days
1 (1-12)5 (1-63)
2 (1-4)4 (1-10)
7 (2-12)4 (2-64)
ICANS: all, ≥G3, % 17, 3 13, 3 10, 3
HLH/MAS, % — 5 ? 7 (lfts)
Infections: all, ≥G3 % 69, — 40, 13 —, 19
Toci/steroid/anakinra use, % 52/15/0 76/52/23 79/21/21
KarMMa(n = 128)
EVOLVE(n = 62)
CARTITUDE-1(n = 29)
ORR, % 73 (66-81) 92 100
sCR/CR, % 33 36 86
MRD neg ≥10-5, %(of evaluable) 94 84 81
PFS, DoR,months 8.8/10.7 NR* NR**
Screened Apheresed Treated
150140128
—353529
? This was not listed at MAS/HLH, I am just speculating àcould this have been early MAS
* 300 x 106 cell dose cohort (lowest) = PFS 9.3 months, other med F/U = 8.8 and 2.3 month ** 9 mo PFS = 86%
Co-provided byPatel K. ASCO 2020 Discussant
EVOLVE BCMA CAR T StudyLook at that waterfall!
EVOLVE: Deep tumor burden reduction across dose levels
Max
imum
per
cent
age
decr
ease
300 x 106 CAR T cells 450 x 106 CAR T cells 600 x 106 CAR T cells
Serological responses* were observed in all patients treated at 450 x 106 and 600 x 108DLs
* Involved serum or urine parapretein, free light chains. ^ Patient with baseline extramedullary plasmacytoma.
Co-provided byPatel K. ASCO 2020 Discussant
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
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
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
Lonial S et al. Lancet Oncol 2020;21(2):207-21.
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%
Lonial S et al. Lancet Oncol 2020;21(2):207-21.
ModeratorNeil Love, MD
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
Co-provided by
Thank you for joining us!
CME and MOC credit information will be emailed to each participant within 5 days.