1. Multiple Myeloma Research Foundation
MMRF News and Updates
PMMNG Meeting
March 11, 2017
Mary DeRome
Multiple Myeloma Research Foundation

2. Progress for Myeloma Patients10 40 3 % ×
DRUGS
IMPROVEMENT 5 IN
-YEAR
LIFE SPAN
IN THE LAST
DECADE
SURVIVAL
FOR PATIENTS

3. MMRF/MMRC Founded in 1998 Funds worldwide research
Builds myeloma community
Partners with MMRC
Founded in 2004
Supports 25 institutions
Conducts tissue banking
Facilitates phase I/II trials

4. MMRF Precision Medicine Model

5. Data Analysis: MMRF Researcher Gateway
CoMMpass℠ data is available through our open-access platform—the MMRF Researcher Gateway—to drive discoveries.
Integrates clinical, laboratory, genomic data; advanced visualization, analytics
Enables population stratification, biomarker and target discovery
Enables researchers to connect, and share analyses, results, insights
Incorporates existing data sets; definitive MM research resource

6. Testing Hypotheses
A new model, the Translational Network of Excellence, was established to accelerate findings from preclinical research to the clinic.
Network priorities:
New targets/drugs validation
Immune efforts
MM-related malignancies
Minimal Residual Disease (MRD)

7. Moving to the Clinic: MMRC
By integrating 25 leading centers, the MMRC has performed over 73 trials with more than 35 agents.

8. MMRF CoMMpass STUDY AS CORNERSTONE
Longitudinal Clinical Data and Molecular Profiling
COMPLETED ENROLLMENT: 1,200+ newly diagnosed patients
DURATION: ~10 years
SITES: 75 Community and Academic Cancer Centers
INDUSTRY PARTNERS: Takeda, Amgen, Janssen, BMS
Centralized Molecular Tests
Flow cytometry & BRAF mutations
RNA sequencing expression analysis
Whole exome DNA sequencing
Whole genome chromosome analysis
Cytospin slides for FISH
Biorespository of PBMNC, plasma Tumor

9. PATIENT questions we’ve been able to answer
Should I do a transplant?

10. PATIENT questions we’ve been able to answer
Should I be on 3 drugs?

11. PATIENT questions we’ve been able to answer
I have del17p.
Am I high risk?

12. PATIENT QUESTIONS WE MUST ANSWER
What treatment (combination) should I start on? should I stay on? Can we prevent this disease?

13. No Two Patients Are The Same
Integrative analyses using CoMMpass data will help identify patients at greater risk of progression and optimize their treatment

14. Additional Data for Relapsed Patients
The MMRF continues to build the data bank with clinical- grade sequencing of 500 relapsed patients.
CD138 Enrichment/ library prep
Exome capture processing
Sequencing HiSeq rapid mode
Report generation and review
Sample receipt
Sequence analysis
Day 0
Days 1–3
Day 4
Days 5–6
Days 6–8
Day 9
ONCOSEQ 1700

15. “Actionable” Alterations in MM
MMRF PM efforts have identified molecular alterations for which there are drugs in the clinic
KRAS and NRAS
(40%)
BRAF
(8%)
CDKN2C and CCND1
(18%)
PI3K-AKT
(5%)
FGFR3
IGF1R and ALK
IDH1/2
MyD88
(3%)
Others
(11%)

16. Beyond Single Hypothesis Testing: Master Protocols
Functional High Risk Patients
RAF/RAS mutations
t(11;14)
IPD
Profiling for alterations (NCT )
No detectable “actionable” alterations
IPD +Immune checkpoint
MAPKi
+ IPD
IDH activating mutations
IDHi
CCND1 activating alteration
CDKi
PI3K/AKT activating alterations
AKTi
BCLi+ IPD
BCLi
FGFR3 activating alterations
FGFRi

17. Precision Medicine Trials
The MMRC is launching precision medicine trials using the information we have gathered from our MMGI and CoMMpass initiatives
MDM2 – 17p deletion
B-raf/MEK – mutations in Ras pathway genes
FGFR3 – activating mutations in a growth receptor
The MMRC has also opened 4 trials to date to test new immune agents such as PDL-1, Elotuzumab, and CD38 Mabs and is collaborating with other institutions on additional immune agent trials

18. IBRANCE® (palbociclib)
Machine Learning -GNS
New insights on high risk disease are emerging from analyses with GNS and were presented at last upcoming ASH meeting in Dec.
IBRANCE® (palbociclib)
dinaciclib
AT7519
OTS167