June 20, 2024
Making Sense of Treatment
IMWG Conference Series:
1
Thank you to our sponsors!
2
TOPICS TO BE COVERED
MGUS, SMM, & DYNAMIC MODELING OF PROGRESSION ICELAND Updates
FRONTLINE THERAPY
MRD Update & MRD2STOP Trial BELANTAMAB: DREAMM-7 and DREAMM-8 Trials CAR T Updates: Fast CAR BISPECIFICS: Teclistamab Real-World Data
VENETOCLAX: CANOVA Update
4
HR SMM: Risk stratification
• 50% risk of progression at 2 years is a reasonable definition of high-risk group to target
– Depend on the risk of intervention
• Multiple risk assessment models have been developed
– Original and or updated Mayo system (20/2/20)
– Spanish method
– IMWG risk score
– Dynamic models
5
Dynamic Modeling of Progression
6
ICELAND UPDATES
7 ICELAND UPDATES
Sverrisdottir
et al.
of Internal Medicine 2024
S.
Annals
Eythorsson E. et al. Annals of Internal Medicine 2024
istopmm.com/riskmodel Eythorsson E. et al. Annals of Internal Medicine 2024
Screening changes the clinical presentation of MM
Any CRAB criteria present at diagnosis
OR=0.11 95%CI: 0.002-0.96; p=0.03
Acute presentation
OR: 0.24 95%CI: 0.05-0.98; p=0.047
In Manuscript, S. Rögnvaldsson et al
Control Arm
Intervention Arm
Recent iStopMM Findings
Obesity Linked to MGUS
Screened MGUS NOT LINKED to Autoimmunity
Prediction of Need for Bone Marrow
Changing the Face of Myeloma
Less CRAB
–
FRONTLINE THERAPY
Isatuximab VRd... New Standard of Care?
13
DARA VRd vs VRd: PERSEUS Trial Update
(Sonneveld et al, EHA 2024)
Sonneveld P, Moreau P, Dimopoulos MA, et al. Daratumumab + bortezomib/lenalidomide/dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma: analysis of minimal residual disease in the PERSEUS trial. Presented at: EHA 2024 Congress; June 15, 2024; Madrid, Spain
14
i2TEAMM:
FDA ODAC Meeting on MRD as an
Early Endpoint for RRMM Clinical Trials
15
IMF
Dr.
The i2TEAMM Executive Team
IMF Mission
Dr.
16
Dr. Bruno Paiva (CIMA Laboratory Diagnostics, University of Navarra Pamplona, Spain)
Nikhil Munshi (Jerome Lipper Myeloma Center, Dana-Farber Cancer Institute—Boston, MA)
Dr. Qian Shi The Mayo Stats Team (Mayo Clinic—Rochester, MN)
Chief Scientific Officer
Brian G.M. Durie
Dr. Kenneth Anderson (Dana-Farber Cancer Institute and Harvard Medical School Boston, MA)
Dr. Jesus San Miguel Miguel (Clinica Universidad de Navarra Pamplona, Spain)
International Independent Team for Endpoint Approval
of Myeloma Minimal Residual Disease (i2TEAMM)
Academic Sites
CC-17 17
International Independent Team for Endpoint Approval
of Myeloma Minimal Residual Disease (i2TEAMM)
Academic Sites and Industry Global Trials
CC-18 18
IMF Mission
ODAC Votes in Favor (12-0)
19
High Individual-Patient-Level Correlation Supports Consideration of Early Endpoint For Accelerated Approval
• Consistent high individual-patient-level correlations provide strong evidence that 9 months MRDneg-CR rate at 10-5 threshold reasonably likely predicts clinical benefit of PFS in NDTE, NDTinE and RR MM populations
‒ Promising trial-level correlations pooling 3 populations provide supportive evidence
‒ Similar results were seen for 12 months MRDneg-CR rate at 10-5 threshold
‒ Similar results were seen for OS, except in the scenarios with low events
MRDneg-CR rate classified at 10-5 threshold at 9 and 12 months IS reasonably likely to predict clinical benefit in NDTE, NDTinE, and RR MM settings
CC-20
20
9 months MRDneg-CR Status, Classified at 10-5 Threshold
Clinical Endpoint: Progression-Free Survival
PFS in all 3 Populations
MRD Negativity Strongly Associated with Longer
CC-21
HR=0.29 (0.24-0.37) HR=0.24 (0.16-0.36) HR=0.31 (0.20-0.46) Patients at Risk MRDneg 533 456 246 130 49 3 MRDpos 1412 1036 576 221 62 2 Patients at Risk MRDneg 133 110 47 16 7 1 0 MRDpos 1585 910 265 61 23 1 0 Patients at Risk MRDneg 104 89 51 17 MRDpos 845 426 200 49 0 20 40 60 80 100 0 12 24 36 48 60 Months % Alive and ProgressionFree 65 NDTE MM Stratified Log-rank P-value < 0.0001 MRDneg MRDpos Months 0 20 40 60 80 100 0 12 24 36 48 60 72 % Alive and ProgressionFree 70 NDTinE MM Stratified Log-rank P-value < 0.0001 MRDneg MRDpos 0 20 40 60 80 100 0 12 24 36 45 RR MM Stratified Log-rank P-value < 0.0001 Months MRDneg MRDpos Stratified by studies 21
47/83 able to discontinue maintenance
40 MRD negative at 10-7: 3-year PFS was 85%
5 [11%] disease progression; 6 [13%] became MRD positive at 10-6
22
HEM
(Hodgkin/B-ALL) HIGH RATE OF SUSTAINED MRD NEGATIVITY
Abstract #106: MRD2STOP Trial (ASCO 2024)
2 developed 2nd
Cancers
DREAMM-7 TRIAL (ASCO 2024)
23
DREAMM-7 TRIAL (ASCO 2024)
24
DREAMM-8 TRIAL (ASCO 2024)
25
DREAMM-8 TRIAL (ASCO 2024)
26
BELANTAMAB MAFODOTIN
Is Bela Back?
27
Fast CAR-T (GCO12F) at EHA 2024
FRONTLINE GCO12F .. FasT CAR T : Newly diagnosed high risk patients
novel manufacturing gives * young phenotype * T cells
VRd followed by CAR T as induction
ORR 100 % and MRD negative @ 10-6 also 100%
Well-tolerated : all CRS grade 1 or 2 within 4 days EXCELLENT RESULTS : PFS and OS AWAITED
28
Comparable ORR to MajesTEC-1
29 Abstract
Real-World Data (ASCO 2024)
7536: Teclistamab
for t[11;14];
HIGH or 1q+
30
(ASCO 2024) Benefit
BCL2
Abstract 7510: Venetoclax-CANOVA Trial
CONCLUSIONS
ANY OTHER KEY TAKEAWAYS?
- New agents
IMMUNE Therapies
- Testing/Biology
- The Future for Myeloma Care ???
… Prospects for Cure?
31
-
2024 ASCO and EHA Key Takeaways
32
We Want to Hear From You!
Feedback Survey
At the close of the meeting a feedback survey will pop up. Click “continue” to complete the survey. This will also be emailed to you shortly after the workshop.
Please take a moment to complete this survey.
Thank you to our sponsors!
34