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Myeloma in 2025
Kenneth C. Anderson, M.D.
Jerome Lipper Multiple Myeloma CenterDana-Farber Cancer Institute
Harvard Medical School
Disclosurese
Kenneth C. Anderson, MD
• Advisory Board: Millennium-Takeda and Gilead
• Scientific Founder: Oncopep, C4 Therapeutics
Prevalence of MGUS
• Serum samples from 21,463 of 28,038 residents ≥
age 50
• 394 (3.2%) MGUS
• 4% men vs 2.7% women, p < 0.001
• 5.3% > age 70 vs 7.5% > age 85
• < 1.0 g/dl 63.5%; ≥ 2.0g/dl 4.5%
• Reduced uninvolved Ig 27.7%
• Monoclonal urinary light chain 21.5%
Kyle RA et al. NEJM 2006 354:1362
27%58%20.853High-risk (All 3 factors abnormal)
18%37%10.1226High-Intermediate-risk (Any 2 factors abnormal)
10%21%5.4420Low-Intermediate-risk (Any 1 factor abnormal)
2%5%1449Low-risk (serum M spike<1.5g/dL, IgG subtype, normal FLC ratio 0.26-1.65 )
Risk stratification model
ARP at 20 years with death as a competing
risk
Absolute risk of
progression (ARP) at 20 years
Relative risk
No. of patients
Risk Group
Rajkumar SV et al. Blood 2005;106:812-817
Risk Stratification Model for MGUS
In 2025 Monoclonal Gammopathy (MG)(No Longer of Undetermined Significance)
1. Already Mass Spect approaches with increased sensitivity detect more MGUS.
2. By 2025 Screening of the general population will be done annually to detect abnormal clones. This likely will be done not only with SPEP/IFX but also using assays to detect circulating cell free DNA and/or single cell sequencing.
3. Clonal hematopoiesis will be detected correlating withcardiovascular disease, rheumatologic diseases, Alzheimers, and cancer. Diseases will be identified in increasing numbers of individuals with aging long before clinical sequelae, allowing for earlier preventive strategies.
cfDNA ‐ ULP‐WGS
Tumor fraction ≤ 3%
Tumor fraction = 17%
Tumor fraction = 66%
1
0
‐1
1
0
‐1
1
0
‐1
Copy number (log2)
MM_0431
MM_1017
MM_0457
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 17 19 22 X
Ultra Low Pass – Whole Genome Sequencing of 88 MM samples identifies clonal plasma cells
Manier S et al ASH 2016
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2
A B
C D
p < 0.001
p = 0.029
p = 0.015 p = 0.023
≤
Cell‐freeDNAYieldsinBloodPlasmaofMMPatients.ComparisontoAdvancedSolidTumors,byISSStage,byDiseaseStatusandLDH
Myeloma vs solid tumors Myeloma by ISS Stage
Myeloma by disease status Myeloma by LDH
Kis and Trudel et al. Nature Communications, in press.
Summary – Whole exome sequencing of CTCs
cfDNA Allows Discovery-Oriented Sequencing in MM Patients
• Discovery‐oriented low‐pass WGS and WES is possible from cfDNA in MM– Requires sufficient tumor fraction– Cost‐effective markers predict efficiency of cfDNA sequencing
• cfDNA is an excellent proxy for clonal events in BM of MM patients
• cfDNA and BM may reveal distinct subclonal information
• cfDNA is useful as a marker for disease progression and clonal evolution– Potentially useful for non‐secreting MM
Lohr et al ASH 2017
Whole bloodBone marrow
CD138pos. selection
Census-based Mutationcalling
Gene expression
Pick single cell
RNA seqDNA seq
Neg. selection
serial dilution
Single circulating MM cell AnalysisCirculating Single MM Cell Sequencing Reveals
Genetic and Phenotypic Characteristics of MM cells
Adapted from source: Database Center for Life Science
Red: peripheral bloodBlue: bone marrow
In 2025, patients with monoclonal gammopathy
1. No longer will be followed expectantly off therapy
2. Immunologic based intervention will delete the abnormal clone.
3. For example, peptide-based vaccination (CD138, SLAMF7, XBP1, BCMA) in combination (Ab to LAG3 Ab checkpoint)to enhance memory response anti-tumor cell response and delete the abnormal clone.
Vaccines Targeting MM Peptides in Smoldering Multiple Myeloma (Will Treat MGUS in 2025)
•Cocktails of immunogenic HLA-A2-specific XBP1, CD138, CS1 peptides to induce MM-specific and HLA-restricted CTL responses
Clinical trials (LLS TAP Program):
Immune responses to vaccine in all patients including tetramer positive cells and type I cytokines
Lenalidomide with vaccine augments these immune response
Lenalidomide, PDL-1, LAG3, HDAC 6i 241 with vaccine to induce memory Immune response against myeloma
. Bae et al, Leukemia 2011; 25:1610-9.Bae et al, Brit J Hematol 2011; 155: 349-61.Bae et al, Brit J Hematol 2012; 157: 687-701.Bae et al, Clin Can Res 2012; 17:4850-60. Bae et al, Leukemia 2015, 2017
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Stimulator: XBP1us / XBP1sp / CD138 / CS1 Peptides
Baseline (Wk 0) Post-2 Vac (Wk 4) Post-4 Vac (Wk 8)
Post- 6 Vac (1M FW) Post- 6 Vac (3M FW) SUMMARY
Induction of
XBP1/CD138/CS1 Peptides-Specific CTL
by Vaccine
Vaccine Gradually InducesXBP1/CD138/CS1-Specific CTL in SMM patient
% Positive Cells
0
20
40
60
80
100
Naïve CM EM TE
CTLA4
0
20
40
60
80
100
Naïve CM EM TE
PD1
0
20
40
60
80
100
Naïve CM EM TE
LAG3
0
20
40
60
80
100
Naïve CM EM TE
TIM3
MFI
0
100
200
300
400
500
600
Naïve CM EM TE
CTLA4
0
200
400
600
800
1000
1200
Naïve CM EM TE
PD1
0
500
1000
1500
2000
2500
Naïve CM EM TE
LAG3
0
200
400
600
800
Naïve CM EM TE
TIM3
Enhanced Expression of Checkpoint Inhibitors on Memory CTL Induced by Peptide Cocktail
Anti-PDL-1 or LAG3 Enhances Proliferation ofXBP1 Peptide-CD8+CTL Subsets
CD8+ CTL Gated
Total CD8+ CTL CD28+ cells CD38+ cells Central Memory Effector Memory
10% 33% 32% 48% 9%
22% 45% 43% 81% 15%
63% 68% 72% 92% 60%
NoTrt
Anti-PDL1
Trt
Anti-LAG3
Trt
CFSE low
CFSE low: CTL in Proliferation
Peptide Based Vaccination of Early Stage Breast, Colon, Pancreatic, and Prostate CA (XBP1 CTLs mediated killing)
Target Cells
None NK-sensitive: K562 Prostate cancer: LnCaP
Breast cancer: MB231 Colon cancer: SW480 Pancreatic cancer: PL45
Breast cancer: BT474 Colon cancer: WiDr Pancreatic cancer: MiaPaca
3.5
16.8
4.2
4.1
14.3
4.1
6.3
13.8
5.1
None NK-sensitive: K562 Prostate cancer: LnCaP
Breast cancer: MB231 Colon cancer: SW480 Pancreatic cancer: PL45
Controls
HLA-A2+
Tumor cells
HLA-A2-
Tumor cells
Bae et al. OncoImmunology 2014; 3: e970914
Current Diagnosis of Active MM (IMWG)
Bone marrow plasmacytosis > 60%
Abnormal FLC ratio > 100 (involved kappa) or <0.01 (involved lambda)
Focal bone marrow lesions on PET-CT and/or MRI
Protocols of novel agents/immune therapies to delay or prevent progression of smoldering to active MM.
Rajkumar et al. Lancet Oncol 2015; 12:e538-e548
Even without CRAB features, the following define active MM:
In 2025 Majority of Current Smoldering Multiple Myeloma Will Be Called Multiple Myeloma
Majority of genomic changes in MM are already presentat SMM stage.
Majority of patients with short time to progression to active MM without genomic or clonal evolution actually have myeloma.
SMM will be the minority of patients with clonal progressionassociated with progression of disease, and longer time to progression.
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Complex Landscape of Rearrangements and clonal evolution in Smoldering and Multiple Myeloma Revealed By Whole‐
Genome Sequencing
WGS of 100 matched paired myeloma samples (SMM, ND, relapse/normal) in a cohort of 30 patients:
Complex Genomic Changes Even at
Smoldering Stage
Progression of SMM to MM OccursRapidly Even Without Genomic or Clonal
Evolution
Bolli et al Nature Comm, in press
Progression30 months
Progression 8 months
Limited Change in Number ofStructuralAberrations
Clonal evolution associated with longer time to progression
Prognostic Staging in 2025
International Staging Systems will incorporate targeted sequencing to identify mutations, copynumber alterations, and translocations.
Targeted Sequencing of MM
Custom Target Enrichment
~3 Mb
(Agilent Sureselct)
IGH locus
•Recurrent translocations
2538 SNPs (CNAs)
•~ 100 per chromosome
•Dense tiling on known CNA regions246 genes
•Known myeloma drivers
•Pan‐cancer oncogenes
426 samples• Diagnosis• BM CD138‐purified• Whole genome amp.• NO matched normal
IlluminaHiSeq2000Target >1.5Gbp per
sampleBolli et al BCJ 2016, Bolli et al Leukemia 2018
Copy number and IGH translocations are called with good accuracy
Bolli et al BCJ 2016, Bolli et al Leukemia 2018
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CN and karyotype dominate the landscape of (negative) prognostic variables (426 patients)
PFS OS
TP53 ✔ ✔NRAS ✔ ✕SP140 ✔ ✕APC_del ✕ ✔CYLD_del ✔ ✔FAM46C_del ✕ ✔FAT1_del ✔ ✔FAT3_del ✔ ✔SNX7_del ✔ ✔TP53_del ✔ ✔CDKN2C_del ✔ ✕MYC_amp ✔ ✕PRDM1_del ✔ ✕SP140_del ✔ ✕del1p ✔ ✔amp1q ✔ ✔del12p13.31 ✕ ✔del13 ✔ ✔del16q ✔ ✔del17p13 ✔ ✔t(14:20) ✔ ✔t(4:14) ✔ ✔t(8:14) ✔ ✕
✔ = p < 0.05 on univariate analysis
Sequencing12%
Gene CN50%
Cytogenetics38%
Breakdown of variables with prognostic value by class
p= 3.11e-8
Bolli et al BCJ 2016, Bolli et al Leukemia 2018
All del17p
Treatment of Multiple Myeloma in 2025
Goal: achieve MRD and restore anti-MM host immunity
Initial treatment with fourth generation IMiD, PI, Dex, and MoAb to decrease tumor burden
Then either autologous CAR T cell, autologous peptide stimulated T cell, or allogeneic T cell adoptive immunotherapy
Products will be optimized for memory tumor specific cytotoxicity
,
IFM: RVD and Early vs Late ASCT
RVD armN=350
Transplant arm
N=350p-value
CR 49% 59%
VGPR 29% 29% 0.02
PR 20% 11%
<PR 2% 1%
At least VGPR 78% 88% 0.001
Neg MRD by FCM , n (%)
228 (65%) 280 (80%) 0.001
Attal et al NEJM 2017; 376: 1311-20
Daratumumab (DARA) With Carfilzomib, Lenalidomide, and Dexamethasone (KRd) in Newly Diagnosed Multiple Myeloma: Updated Results of Phase 1b Study
Daratumumab plus KRd is highly effective, with a 100% ORR, including 91% of patients with ≥VGPR and 57% of patients with ≥CR
– Depth of response deepens with longer follow‐up
– MRD‐negative rate at 10–5 was 14%
Daratumumab with KRd was well tolerated
– safety profile is consistent with daratumumab and KRd
There was no adverse impact on stem cell collection (median CD34+
10.6 × 106 cells/kg)
Phase III trial of KRd + Dara ongoing to validate efficacy of 4 drug
induction
28Chari et al, ASH 2017
bb2121: An Anti‐BCMA Chimeric Antigen Receptor T Cell Product Candidate Berdaja et al ASH 2017
• bb2121 is autologous T cells transduced with a lentiviral vector encoding a novel CAR incorporating an anti‐BCMA scFv, a 4‐1BB costimulatory motif to promote proliferation and persistence, and a CD3 T cell activation domain
• Construct demonstrated potent preclinical in vivo activity with low tonic signaling
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bb2121 demonstrates lowantigen-independent signaling
anti-BCMA CARs
IFN
-
bb2121 improves survival and drives tumor clearance in MM mice
Clinical Trial of bb2121: An Anti‐BCMA Chimeric Antigen Receptor T Cell Product
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3 + 3 Dose Escalation of CAR+ T Cells
*1200 x 106 dose cohort no longer planned
Manufacturing success rate of 100%
Study Status(Escalation
Phase)
Cells Collected
N=24
DosedN=21
Evaluable for Response
N=21
Leukapheresis
Screening
bb2121manufacturin
gManufacturingg
(10 days) + release
bb2121 infusion
1st ResponseAssessment (Wk 4)
BM BX
(Wk 4)
BM BX (Wk 2)
Day 0
Clinical deterioration n=3
Berdeja et al ASH 2017
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Conclusion : b2121 Demonstrates Deepening and Durable Responses with Manageable Safety Profile
bb2121 at active doses (150 – 800 × 106 CAR+ T cells)
94% ORR, 89% VGPR or better, 56% CR or better
– Median PFS not reached with follow up of 40 weeks
– MRD negative results in 90% of MRD evaluable patient samples
– Disease progression in 4 patients; 3 of 3 evaluable patients remain BCMA positive at progression
bb2121 manageable through doses as high as 800 × 106 CAR+ T cells
– The 2 reported events of grade 3 CRS resolved within 24 hours
– 1 case of delayed onset, reversible grade 4 neurotoxicity associated with tumor lysis syndrome and CRS
– Patient with highest tumor burden on the trial
– Rapid myeloma response (VGPR) in tumor with low BCMA expression (1% of plasma cells)
Global Pivotal Trial (KarMMa) is open for enrollment
– bb2121 dose range: 150‐300 × 106 CAR+ T cells 31
CAR-T Cells
Recognize a single target
Recognize surface proteins (<10% of tumor specific targets)
Artificial continuous signaling from inserted domains cause either extreme inflammatoryresponses or exhaustion
CAR T cells in 2025 will be optimized for selective memory cytotoxicity and given early to avoid toxicity
.
Can recognize multiple targets (BCMA, CS1,CD138,XBP1)
Recognize intracellular proteins (majority of tumor specific targets)
Immune regulatory mechanisms normal (less toxicity)
Antigen Specific Autologous Anti-MM T Cells
Adoptive therapy with T cells expanded in presence of peptides(PRAME1 Wt1 and Survivin) have achieved CR in relapsed AML.
Bollard et al, ASH 2017
Patients are vaccinated with peptide based (CD138, XBP1, CS1, and BCMA peptides) to generate autologous memory cytolytic T cell anti-MM response
T cells are then harvested by pheresis and expanded ex vivo in the presence of these CD138, XBP1, CS1, and BCMA peptidesto increase memory cytolytic T cells
T cells are then reinfused as adoptive immunotherapy withoutadverse side effects
Vaccinations can then be given subsequently to maintain memory anti-MM specific responses.
In 2025 Peptide Simulated Adoptive Immunotherapy Combined with Vaccination in MM
Normal donor T cells will undergo CRISPR/Cas9 editing to remove native TCR (no GVHD), and transfected to target BCMA and CD138
After induction therapy to reduce tumor burden in newly diagnosed MM, allogeneic BCMA/CD138 CAR T cells are thawed from off the shelf and infused as therapy.
Vaccination post allogeneic CAR T cell treatment as needed with BCMA and CD138 peptides to maintain allogeneic memory anti-MM responses.
In 2025, Off the Shelf Allogeneic Normal Donor CAR T Cells for MM
.
Metrics of Response in 2025
1. Minimal residual disease (MRD) will be defined as 10-6 by single cell sequencing or cfDNA, as well as negative imaging.
2. Complete response will include not only achievement of MRD, but also require restoration of host anti-MM immunity.
3. Once host anti-MM immunity is restored, maintenance therapy will not be needed.
4. Vaccination can then be used sustain memory anti-MM immune response.
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MRD in Multiple Myeloma: Final Analysis IFM2009 Trial
Sensitivity (10‐6) (next generation sequencing) predictsbetter outcome: PFS and OS in both RVD and RVD ASCT arms, including both standard and high risk patients
Requirement to includeMRD in all the upcoming trials
MRD could become the primary endpoint of future trials
MRD will be central in the definition of cure
MRD will be essential to stratify patients:• consolidation randomization?• maintenance randomization?• maintenance duration?• earlier définition of molecular relapses?
Avet-loiseau et al, ASH 2017
Newly diagnosed1st Relapse2nd Relapse
Serial Genomic Profiling Allows for Delineation of Chromosomal Changes Occur with Evolution of MM
N
Will allow for more precise treatment of mechanisms underlying response
Continued Development of Novel Targeted Therapies in 2025
Genomic/epigenomic abnormalities: Target and overcome mechanisms of genomic instability, target genomic/epigenomic abnormalities and their sequelae
Modulate Protein Homeostasis: Target protein degradationTrigger selective protein degradation
Immune Modulation: Trigger host anti-MM immunity
Targeting Mutations in Multiple Myeloma
Morgan GJ, Walker BA and Davies FE. Nature Reviews Cancer. 2012 Chapman et alNature Genetics 2011, Walker et al 2012 Blood, Lohr et al Cancer Cell 2014, Bolli et al
Nat Comm 2014, Walker BA et al Nat Comms 2015
Therapies Targeting Ras Raf MAPK Pathway Achieve OnlyTransient Responses, Combination Clinical Trials Ongoing
Personalized Medicine: Responses to Venetoclax (Target BCL-2) and Bortezomib (Target Bcl-1) byBCL2:BCL2L1 Ratio Among t(11;14)-Positive
Patients with RRMM
(n=9) (n=15)
BCL2:BCL2L1 (BCL-XL) BCL2:BCL2L1
High Low
High BCL2:BCL2L1
Low BCL2:BCL2L1
Gene expression ratio among t(11;14) patients
Kumar et al,, Moreau et al ASH 2016
Integrative Oncogenomic Analysis: Combining Whole Genome, Transcriptome, and Epigenome Identifies Altered Chromatin
Accessibilitiy Landscape and New Targets in Multiple Myeloma
Szalat et al ASH 2017
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Targeting Causes of Genomic Instability
1. Homologous recombination (HR)2. APEX nuclease activity3. Pan nuclease activity4. APOBEC activity
Ongoing Studies• Developed in vitro assays to measure HR, APEX,
nuclease and APOBEC activity• Use these assays for HT screen to identify
inhibitors
Shammas, Munshi, et al 2016
Damaged DNA
Replicative stress Oxidative stress
MYC amplification
ATR
ROSSOD
PL
Apoptosis
Treating Consequences of Genomic Abnormalities Cottini et al Cancer Discovery 2015; 5: 972
ITGB7
Epigenetic Targeting of KDM3A-KLF2-IRF4 in MM
Ohguchi et al Nat Comm 2016; 7:10258
KDM3A catalyses removal of H3K9 mono‐ and di‐methylation in MM
ATPasesATPases
RA190
RA190
RA190
Poly‐Ub‐Substrate
Song et al, Leukemia 2016; 30:1877-86.
Targeting Ubiquitin Receptor Rpn13
IB: anti-β-actin Ab
IB: anti-Ub Ab
Control
RA190-
200n
M
RA190-
600n
M0
50
100
150
%V
iab
le c
ells
Patient1Patient 2Patient 3
p < 0.0001
Patient 4Patient 5
Blockade of Ubiquitin Receptor Rpn13 with RA190 InhibitsMyeloma Cell Growth and Induces Polyubiquitination
Song et al., Leukemia, 2016: 30:1877-86.
Mechanism of Action of Immunomodulatory Drugs
Kronke et al, Science, 2014
Lu et al, Science,2014
Degronimids:Link to ubiquitin 3 ligase complexes
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Degronimids Trigger Degradation of Selective Substrates in Cancer and other Diseases
DEGRONIMID™
TargetProtein
Binding“Warhead”
CereblonLinker
Proteasome“Destroy”
CereblonE3 LigaseComplex
Degrade
RecycleDegradationMachinery
Ub
UbiquitinTag
Ub
UbiquitinTag
Ubiquitin 3 ligases: cereblon, VHL, MDM2
Bradner et al, Science, 2015
Substrates: EGFR, BTK, BRD4,USP7, rpn, STK4, PRPK
Development of Small Molecule Degrader WL40 for Rpn13
WL40 degrades Rpn13, and induces a more robust MM cell death thanparental molecule RA190
Rpn13degradation
DegronimidConstruction
Isatuximab Triggers ADCC, ADPC, CDC, and Lysosomal MM Cell-Death
Tai et al Leukemia 2016;30:399 BCMA GSK2857916Tai et al Blood 2014; Tai & Anderson 2015
Bone Marrow Stromal Cell
GSK2857916MM
ADCC
Apoptotic MM cells
FcRIII
Apoptosis
MM
ADPC
APRIL BAFF
NK ,Monocyte
MM cell lysis
NFB
Inhibition of NFB signaling
A BCMA Auristatin Immunotoxin Induces Strong Anti-MM Effects
FcRII
M engulfing MM
MMAF released at lysosome to induce G2/M arrest followed by apoptosis
Macrophage
GSK2857916 Aurostatin Immunotoxin Targeting BCMA in Relapsed/Refractory Multiple Myeloma
– Median follow-up 6.6 months; study is ongoing
– ORR of 60% in heavily pre-treated MM
– 51% of patients in Part 2 had VGPR or better
– Median PFS 7.9 months
– Well tolerated and side effects manageable
– Thrombocytopenia and corneal events most frequent AEs
– IRRs occurred in only 23% of patients without pre-medication; no IRRs occurred on subsequent infusions
– Additional monotherapy and combination studies are planned
DOR, duration of response; IRR, infusion-related reaction; MM, multiple myeloma; ORR, overall response rate; PFS, progression-free survival; VGPR, very good partial response
53
Trudel et al ASH 2017
BCMA-BiTE-Based Immunotherpaies
MM
T cell
MM cell lysis
BCMA‐BiTE
T cell
T cell
T cellT cell proliferation
T cell
T cell
CD3BCMACytotoxic granule
Hipp, Tai et al Leukemia 2017; 31:1743‐51.
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Screening of general population (cfDNA and single cell sequencing) will identify monoclonal cells and gammopathy without clinical sequelae. Vaccination
strategies will be used to delete clone.
The majority of what is now classified as SMM will be called and treated as MM, since abnormal clone expansion without evolution associated with disease progession.
Targeted sequencing for prognostic staging
Myeloma in 2025 In active MM, combination therapies to reduce tumor burden, likely triplet therapy and MoAb.
Once tumor burden reduced, adoptive autologous or allogeneic cellular immunotherapy will achieve minimal residual disease and restore host anti-MM immunity in many patients with myeloma.
Serial gene/epigenetic profiling will allow for earlier diagnosis of relapses and selected treatment.
Novel agents will target causes and sequelae of genomic/epigenomic abnormalities, protein homeostasis, and modulate host anti MM immunity.
Myeloma in 2025
Combination therapies defined in preclinical studies will be used to treat patients, defined by profiling and informed by biomarkers. This will lead to smaller trials, less cost, and more rapid approval of novel agents.
Collaborative effort of academia, biotech/pharma, NIH/NCI, FDA, and advocacy- International Myeloma Society-will facilitate continued advances.
Long term disease free survival and potential cure of MM will result from 1. achieving minimal residual disease negativity, and 2. restoration of host immunity.
Myeloma Care in 2025United Nations Against Myeloma:
Bench to Bedside Research TeamKenneth AndersonNikhil MunshiPaul RichardsonRobert SchlossmanIrene GhobrialSteven TreonJacob LaubachDeborah DossKathleen ColsonMary McKenneyKim NoonanTina FlahertyKathleen Finn Muriel GannonStacey ChumaJanet KunsmanDiane WarrenCarolyn RevtaAndrea FreemanAlexis FieldsAndrea KolligianJohn FeatherFarzana MasoodNora LoughneyHeather GoddardTiffany PoonNicole StavitzskiRanjit BanwaitShawna CormanHeather GoddardMeghan Marie LeahyCaitlin O’GallagherChristina TripsasKarin AndersonShannon VieraKatherine RedmanAmber WalshSamir AminWanling XieParantu ShahHolly BartelLisa PopitzJeffrey Sorrell
Teru HideshimaConstantine MitsiadesDharminder ChauhanNoopur RajeYu-Tzu TaiRuben CarrascoJames BradnerGullu GorgunJooeun BaeFrancesca CottiniMichele CeaAntonia CagnettaTeresa CalimeriEdie WellerAjita SinghZe TianDiana CirsteaYiguo HuNaoya MimuraJiro MinamiSun-Yung KongWeihua SongDouglas McMillinCatriona HayesSteffen KlippelJana JakubikovaPanisinee LawasutNiels van de DonkEugen DhimoleaJake DelmoreHannah JacobsMasood ShammasMariateresa FulcinitiJianhong LinJagannath PalSamantha PozziLoredana SantoClaire FabreAnuj MahindraRao PrabhalaJake DelmorePuru NanjappaMichael SellitoAvani Vaishnav
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