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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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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

29

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

USA

UK

India

Italy

Japan

Canada

Germany

China

Greece

Taiwan

Australia

IrelandIsrael

Turkey

Austria