2025 IMF Regional Community Workshop Waltham Slides

2025 IMF REGIONAL COMMUNITY WORKSHOP WALTHAM, MA SEPTEMBER 27, 2025

Thank you to our speakers & our sponsors!

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

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Welcome & Introductions Robin Tuohy Vice President, Patient Support International Myeloma Foundation Understanding Myeloma Basics Shonali Midha, MD Dana-Farber Cancer Institute, Boston, MA

IMF REGIONAL COMMUNITY WORKSHOP WALTHAM MORNING AGENDA

(Video) Closing the Gap: Health Disparities in Myeloma Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, Chief Medical Officer, International Myeloma Foundation Advancing Treatment Options Through Clinical Trials Andrew Yee, MD Massachusetts General Hospital, Boston, MA Q&A with Panel Coffee Break Breakout: Frontline or Relapsed Treatment Approaches -NDMM: Getting Started with Myeloma Management Shonali Midha, MD -RRMM: Continuing the Myeloma Treatment Journey Andrew Yee, MD

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Housekeeping Items Presentation Slides: Are available by scanning the QR code, Instructions are on the QR code handout on each table.

Program Evaluations: Please be sure to complete your program evaluation and return your evaluations at the end of today.

Restrooms: Outside the meeting hall, take a left and then proceed towards the hotel reception. Bathrooms are on the right just before reception desk.

Badge Holders: Please return your badge holders and we can recycle them.

We greatly appreciate your time and feedback!

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

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Research – SAB

Scientific Advisory Board

S. Vincent Rajkumar, MD IMF Board Chair

Thomas Martin, MD UCSF, Helen Diller Family Comprehensive Cancer Center

Wee Joo Chng, MD National University of Singapore

María-Victoria Mateos, MD, PhD University of Salamanca

Vania Hungria, MD, PhD Santa Casa de São Paulo

Joseph Mikhael, MD, MEd, FRCPC, FACP IMF Chief Medical Officer

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

Sigurður Yngvi Kristinsson, MD, PhD University of Iceland

Philippe Moreau, MD University Hospital of Nantes

NIkhil Munshi, MD Dana-Farber Cancer Institute

Shaji Kumar, MD Mayo Clinic

Jesús San Miguel, MD, PhD University of Navarra

Sagar Lonial, MD, FACP Winship Cancer Institute, Emory University

Saad Zafar Usmani, MD, MBA, FACP, FASCO Memorial Sloan Kettering Cancer Center

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Understand the Myeloma Journey

• Support Groups empower patients & care partners with information, insight & hope • The IMF provides educational support to a network of over 150 myeloma specific groups

150+ US Support Groups Over 200 Support Group Visits/year

Support – Groups

The IMF Support Group Team is Here For You! Shared Experiences Help to Better

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Boston-Dana Farber, MA  Meets virtually on the 2nd Wednesday of each month at 5:30 PM



Prospect, CT  Meets virtually, with quarterly in-person on the 2nd Tuesday of each month at 6 PM



Greater Rhode Island  Meets hybrid on the 1st Wednesday of each month at 6 PM



Manchester, NH  Meets virtually on the 3rd Wednesday of each month at 6 PM



Cape Cod, MA  Meets in-person on the 2nd Tuesday of each month at 3 PM



Central MA  Meets hybrid on the 2nd Monday of each month at 6 PM



UConn (Farmington), CT  Meets virtual on the 1st Thursday of each month at 3:30 PM



Fairfield, CT  Meets virtually on the 1st Tuesday of each month at 7 PM



Portland, ME  Meets virtually on the 4th Wednesday of each month at 6 PM



Burlington, VT  Meets virtually on the 3rd Tuesday of each month at 5 PM

Support – Local Groups



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Special Interest Groups Special interest groups are designed as a supplemental support for specific populations of patients, in addition to their local Support Groups  Smolder Bolder

 MM Families

 Founded in 2021  For patients & care partners with young children

Click here for more inf o

 High Risk Multiple Myeloma

 Las Voces de Mieloma

 Founded in 2022  For Spanish speaking patients & care partners

 Living Solo & Strong

 Founded in 2022  For patients without a care partner

 Founded in 2023  For smoldering myeloma patients & care partners

 Founded in 2023  For high-risk myeloma patients & care partners

 Veterans SIG

 Founded in 2025  For those who served our country

 Care Partners Only  Founded in 2024  For myeloma care partners only

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Support – InfoLine & Myelo

CLINICAL TRIALS MATCHING ENGINE

Seamlessly matching patients to the latest clinical trials.

• Discover clinical trials tailored to your myeloma journey with the IMF. • Filter by diagnosis, treatment, and location to find the best fit for you.

Clinical Trials Matching Engine Usage 3,638

Jan-25

4,355

Feb-25

4,794

5,217

owth r G 40% Mar-25

Apr-25

5,455

May

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Resources to Find Clinical Trials and Avoid Bias

IMF Infoline US & Canada: 800-452 CURE (2873) Worldwide: 1-818-487-7455 infoline@myeloma.org Clinicaltrials.gov https://clinicaltrials.gov/

Just ASKTM Implicit Bias Training from Association of Community Cancer Centers website. Accessed March 15, 2024. https://www.accc-cancer.org/home/attend/webi nar-template/2022/07/25/on-demand/just-ask-i ncreasing-diversity-in-cancer-clinical-research

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WRITTEN EDUCATION

Understanding Booklets Tip Cards

Myeloma Minute Weekly Updates Myeloma Today Quarterly News

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2025 Locations

4 PATIENT & FAMILY SEMINARS including world-renowned experts COMMUNITY 10 MYELOMA

WORKSHOPS including local myeloma experts

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

Education – In Person Programs

Live Patient Education

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2025 Live Patient Education • •

Boca Raton, FL – March 14 – 15 Philadelphia, PA – May 2 – 3

•

Los Angeles, CA – August 15 – 16

•

Chicago, IL – October 3 – 4

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

Myeloma Community Workshops •

Virtual-March 4-replay on myeloma.org

•

San Mateo, CA - March 29

•

Atlanta, GA - April 5

•

Edina, MN - April 26

•

Denver, CO - June 21

•

Virtual – July 29 – replay on myeloma.org

•

Seattle, WA - August 9

•

Waltham, MA - September 27

•

Raleigh-Durham, NC - November 15

•

Virtual – November 18

Education – Programs

Patient & Family Seminars

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2. Eliminate Financial Barriers: We advocate for policies that allow myeloma patients access to treatments and supportive care interventions without facing financial hardships.

3. Advance Myeloma Research: We advocate for annual appropriations funding for myeloma research and the advancement of clinical trial eligibility and research protocols that ensure representation from diverse populations.

The IMF Grassroots Advocacy Program is multi-faceted and growing

• Advocacy Training & Leadership Development • Policy and Legislative Education • Grassroots Campaign Planning • Health Policy Forums & Roundtables • Advocacy Resource Development • Storytelling and Personal Narratives

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Advocacy – US Priorities

1. Ensure Access to Care: We advocate to ensure all myeloma patients have equitable, comprehensive, patient-centered care without insurance barriers that limit options or delay treatment initiation.

Scan for Upcoming Programs and Events!

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

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Understanding Myeloma Basics Shonali Midha, MD Dana-Farber Cancer Institute, Boston, MA

Understanding Myeloma Basics Shonali Midha, MD Dana-Farber Cancer Institute ,Boston, MA

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OBJECTIVES



Review the basics of blood and cancer



Define multiple myeloma and its key features



Discuss the staging and classification of myeloma



Outline the approach to therapy of myeloma

How common is Myeloma in the US? Estimated New Cases in 2024

36,110

% of All New Cancer Cases

1.8%

Median Age At Diagnosis

69 years

How common is Myeloma?

Percent of New Cases by Age

Rate of New Cases per 100,000 Persons by Race/Ethnicity & Sex https://seer.cancer.gov/statfacts/html/mulmy.html dated

What Causes Myeloma? How/Why Did I Get This?

Environmental Factors: • Exposure to some chemicals • Radiation exposure

Examples:  Agent Orange  Burn pits  Pesticides, Herbicides  Firefighter/First Responder exposures

Individual Factors: • Age • Family History of related disorders • Personal History of MGUS or SMM • Obesity

VA Study Documents Health Risks for Burn Pit Exposu res Leukemia and Multiple Myeloma Set to Be Added to List of Conditions Linked to Burn Pits

In most cases, the honest truth …..

WE DON’T KNOW

Multiple Myeloma Diagnosis Can Be Challenging

Fatigue

Bone Pain

Anemia Kyle RA. Mayo Clin Proc. 2003;78:21-33.

What is the Connection Between Bone Marrow & Myeloma ?

Hematopoietic stem cell

Red Blood Cells

White Blood cell

Platelets

Carry Oxygen

Fight Infection

Prevent Bleeding

Photo Credit

This Photo by Unknown Author is licensed

Graphic Credit: Teresa Miceli

Understanding (Mono)clonal Plasma Cells

Heavy Chain = M-Spike  65% IgG – most common  20% IgA – associated with AL Amyloid  5% to 10% light chain-only (kappa, lambda)  Less common: IgD, IgE, IgM eGFR = estimated glomerular filtration rate; M-spike = monoclonal spike; Ig = Immunoglobulin

Image Credit: IMF Patient Handbook

Heavy Chain: G, A, M, D, E

• • • • • •

AL-Amyloid POEMS Light or Heavy Chain Deposition Disease MGCS = Clinical MGRS = Renal MGNS = Neuro

Is Myeloma the Only Protein Disorder?

(Monoclonal Gammopathy of Undetermined Significance)

SMM1-5,8

(Smoldering Multiple Myeloma)

Active Multiple Myeloma6-8

Clonal plasma cells in bone marrow

<10%

10%-60%

>10%

Presence of Myeloma Defining Events

None

None

Yes

Likelihood of progression

~1% per year

~10% per year

Not Applicable

Treatment

No; observation

Yes for high risk*; No for others

Yes

Condition

MGUS1-4

* In clinical trial MGCS = clinical significance; MGRS = Renal significance; MGNS = Neuro significance

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Multiple Myeloma and Myeloma Defining Events Clonal Bone Marrow ≥ 10% Or Bony/Extramedullary Plasmacytoma AND any one or more Myeloma Defining Events (MDE)

SLiM CRAB

S Clonal BMPC ≥ 60% Li FLC ratio >100

M

>1 focal lesion* by MRI

BMPC = Bone marrow plasma cells FLC = serum free light chain * >5 mm

Rajkumar SV, et al. Lancet Oncology. 2014; 15:e538-e548.

Kyle RA, et al. Leukemia. 2010; 24(6):1121–1127.

C alcium elevation R enal complications A nemia B one disease 29

Testing For Myeloma: Blood & Urine Test Name

What it means

CBC + differential Complete metabolic panel

Hemoglobin, WBC, Platelets Creatinine, Calcium, Albumin, Liver function

Part of staging and risk Beta-2 Microglobulin (B2M) Lactate Dehydrogenase (LDH) stratification Serum Immunofixation and Protein electrophoresis (SPEP+IFE) Immunoglobulins (G, A, M, D, E) Free light chain assay with kappa/lambda ratio Urine immunofixation & protein electrophoresis (UPEP+IFE)

Measures the level of normal and clonal protein Identifies the type of clonal protein

C R A B

This Photo by Unknown Author is licensed under CC BY-SA-NC

S Li M

Measures the level of normal and clonal protein Identifies the type of Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-3548. Ghobrial IM, et al. Blood. 2014;124:3380-3388; mSMART.org; NCCN.org CBC= Complete Blood Count; WBC = White Blood clonal protein Cell

Testing For Myeloma: Imaging Imaging: – Skeletal survey: Series of X-rays; less sensitive than other techniques

– Whole body low dose (CTWB-LD CT ) – Positron Emission Tomography (PET/CT) – Magnetic Resonance Imaging (MRI)

S L i M

Healthy bone versus myeloma bone disease

C R A B

This Photo by Unknown Author is licensed under CC BY-NC-ND

Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-3548. Ghobrial IM, et al. Blood. 2014;124:3380-3388; mSMART.org; NCCN.org

Testing For Myeloma: Bone Marrow This Photo by Unknown Author is licensed under CC BY-SA

Bone marrow genetics • Cytogenetics • Fluorescence in situ hybridization (FISH) • Next generation sequencing (NGS) High Risk FISH Results* Image Credit: IMF Patient Handbook

Bone marrow biopsy & aspirate • Bone marrow plasma cells (%) • Congo Red staining if concern for AL-Amyloid Rajkumar SV, et al. Lancet Oncol.

2014;15:e538-3548.

Ghobrial IM, et al. Blood. 2014;124:3380-3388; mSMART.org; NCCN.org

Deletions

n

Translocationsg SooGain in m o C

1pt(4;14) ia r e t Crit(14;16) 17pd te a d (p53del) t(14;20) Up *15-20% of people with NDMM

1q+

What is (the importance of) Myeloma Staging & Risk Stratification?

Putting It Together

• Updated as new information becomes available • Helps to guide therapy and measure response to treatment • Provides some prognostic value • Standardizes terminology in medical practice Revised International Staging System (R-ISS), adding LDH & FISH

High Risk FISH Results* Deletion s

Translocatio ns

Gai n

Stag e

Result

1

β2M < 3.5 mg/l Serum albumin ≥ 3.5 g/dl Standard-risk CA by FISH Normal LDH

2

Not R-ISS stage I or III

β2M ≥ 5.5 mg/L and either 1pt(4;14) 1q+ 3 High-risk CA by FISH 17pt(14;16) OR High LDH (p53del) CA = chromosomalt(14;20) abnormalities; LDH = Lactate Dehydrogenase; FISH = Fluorescence in situ hybridization

Risk Feature

R2-ISS Score

ISS-2

1

ISS-3

1.5

1q+

0.5

del(17p)

1

t(4;14)

1

LDH, High

1

R2-ISS Risk Scoring System Stage

Score

Low

0

LowIntermediate

0.5-1.0

IntermediateHigh

1.5-2.5

High

Image Credit: IMF Patient Handbook

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What is the Myeloma Treatment Landscape?

L O T # 1

Initial Therapy (a.k.a. Frontline, Induction) Quad Therapy (ex. CD38+ MoAb + VRd) HD-Melphalan + Stem Cell Transplant (ASCT)

Or

Consolidation Therapy

Maintenance LOT #2

Treatment for Relapse

LOT #3

Treatment for Relapse

LOT #4

Treatment for Relapse

LOT #5

Treatment for Relapse

LOT #6

Treatment for Relapse ASCT = Autologous Stem Cell Transplant; MoAb=monoclonal antibody; VRd=Velcade, Revlimid, dexamethasone

Supportive Care and Living Well

Drug Class Overview Class

Drug Name

Abbreviation

IMiD immunomodulatory drug

Thalomid (thalidomide)

T or Thal

Revlimid (lenalidomide)

R, Rev, Len

Pomalyst (pomalidomide)

P or Pom

Velcade (bortezomib)

V or Vel or B

SC/SQ or IV

Kyprolis (carfilzomib)

C or K or Car

IV

Ninlaro (ixazomib)

N or I

Oral

Cytoxan (cyclophosphamide)

C, CTX

Alkeran or Evomela (melphalan)

M or Mel

Oral IV

Decadron (dexamethasone)

Dex or D or d

Prednisone

P or Pred

Monoclonal Antibodies

Darzalex (daratumumab) Sarclisa (isatuximab) Empliciti (elotuzumab)

Dara Isa Elo

IV or SQ IV IV

XPO1 Inhibitors

Xpovio (selinexor)

X or Sel

Oral

Proteasome inhibitor

Chemotherapy

Steroids

SC or SQ = Subcutaneous, Under the skin; IV = Intravenous

Administration Oral (PO)

Oral IV

Drug Class Overview Class

Drug Name

Abbreviation

Administration

Peptide Drug Conjugate*

Pepaxto (Melphalan Flufenamide)

Melflufen

IV

BCMA Targeted Antibody Drug Conjugate (ADC)*

Blenrep (belantamab mafodotin-blmf)

Bela, Belamaf, or B

IV

Abecma (idecabtagene vicleucel)

Ide-cel

CAR T Cell therapy

Bispecific Antibodies

Pipeline

IV

Carvykti (ciltacabtagene vicleucel)

Cilta-cel

Tecvayli (teclistimab) Talvey (Talquetamab) Elrexfio (Elranatamab) Lynozyfic (Linvoseltamab)

Tec Talq Elra Linvo

SC/SQ IV

Cevostamab, Iberdomide, Mezigdomide, Venetoclax. Sonrotoclax, anitocel, arlo-cel, Etentamig (ABBV-383), ISB2001, JNJ-79635322 ………MUCH * These agents are currently off the market but available through special programs MORE TO COME!

SC or SQ = Subcutaneous, Under the skin; IV = Intravenous

Measuring Disease Response: IMWG Response Criteria

sCR Molecular CR

Response

Myeloma Cells & Protein

MRD negative*

Negative by next generation flow (NGF) or next generation sequencing (NGS) (minimum sensitivity 1 in 10-5 nucleated cells or higher)* mCR AND normal Free Light Chain ratio, Bone Marrow negative by flow, 2 measures CR AND negative PCR

CR

Complete Response: Negative immunofixation (IFE); no more than 5% plasma cells in BM; 2 measures

VGPR

Very Good Partial Response: 90% reduction in myeloma protein

PR MR SD PD

Partial Response: at least 50% reduction in myeloma protein Minimal Response Stable Disease: Not meeting above criteria Progressive Disease: At least 25% increase in identified myeloma protein from lowest level

MRD = Minimal Residual Disease sCR = Stringent Complete Response; BM = Bone Marrow

Kumar, S., Paiva, B., Anderson, K. C., Durie, B., Landgren, O., Moreau, P., ... & Dimopoulos, M. (2016). International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. The lancet oncology, 17(8), e328-e346.

When Do I Need A New Treatment?

• Not every relapse requires immediate therapy • Each case is different

Asymptomatic biochemical relapse on 2 consecutive assessments

Consider Observation Monitor Carefully

Kumar et al. NCCN Guidelines. Multiple myeloma. V4.2018.

Asymptomatic high-risk disease or rapid doubling time or extensive marrow involvement Consider Treatment Patient-/Disease-Specific Monitor Carefully

Symptomatic or extramedullary disease

Initiate Treatment

Targets on the Myeloma Cell Surface and Therapeutic Antibodies Bi-Specific Antibodies Talvey (Talquetamab) CAR-T

Bi-Specific Antibodies CAR-T GPRC5D

FcRH5

SLAMF7

CD38 Monoclonal Antibodies Daratumumab and Darzalex Faspro Sarclisa (Isatuximab) TAK-079 MOR202

Antibody Drug Empliciti (Elotuzumab) Bi-Specific Antibodies

BCMA

Immune Therapies Abecma (Ide-cel CAR-T) Carvykti (Cilta-cel CAR-T) Tecvayli (Teclistamab) Elrexfio (Elranatamab) Other CAR-Ts Other Bi-Specific Antibodies

Antibody Drug Conjugates

How it works: An antibody directed at a target (BCMA) combined with a cytotoxic agent (chemotherapy) ADC = Antibody-Drug Conjugate BCMA = B-Cell Maturation Antigen ADCP/ADCC = Antibody-Dependent Cellular Cytotoxicity & Phagocytosis Image Credit: https://creativecommons.org/licenses/by-nc/3.0/

Bispecific Antibodies: Mechanism of Action • Incorporates 2 antibody fragments to target and bind both tumor cells and T cells • Brings target-expressing MM cells and T cells into close proximity, enabling T cells to induce tumor-cell death

Targets of Bispecific Molecule Vary Agent

Tumor Cell Target

T-Cell Target

Teclistamab Elranatama b Linvoseltam ab

BCMA

CD3

Talquetama “Off the Shelf” AdvantageCD3 GPRC5D b • No manufacturing process, unlike CAR T-cell Cevostamab FcRH5 CD3 therapy (but like ADC/belantamab therapy) • Thus, no delay between decision to treat and administration of drug ADC = Antibody-Drug Conjugate; BCMA = B-Cell Maturation Antigen; CD3 = Cluster of Differentiation 3; FcRH5 = Fc receptor-homolog 5; GPRC5D = G-protein coupled receptor family C group 5 member D Image Source: Shah N, et al. Leukemia. 2020;34:985–1005. Creative Commons License: CC BY 4.0. Barilà G, et al. Pharmaceuticals (Basel).

The Process of CAR T Cell Therapy 1 CAR T therapy recommended . Insurance approved and ready to move forward.

2 a

Apheresis to collect T Cells

T Cells

ll e C on T usi f In

3

2b

Bridging therapy, if needed; Lymphodepleting therapy when CAR T cells are ready

CAR T= Chimeric Antigen Receptor T Cell; LOT = Lines of Therapy

Hucks G, Rheingold SR. Blood Cancer J. 2019;doi:10.1038/s41408-018-0164-6.

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Close monitoring and Management of side effects

5 HOME!

The Evolution of Myeloma Therapy

Now

VD Rev/Dex CyBorD VTD VRD KRD D-VMP DRD

ASCT (?)

Tandem ASCT (?)

Front line treatment

Induction

New

D-VRD Isa-VRD D-KRD Isa-VRD

Consolidation

“More” induction?

Nothing Thalidomide?

Bortezomib Ixazomib Lenalidomide Combinations

Bortezomib Panobinostat Lenalidomide Daratumumab Carfilzomib Ixazomib Pomalidomide Elotuzumab Selinexor Isatuximab Belantamab mafodotin* Melphalan flufenamide* Idecabtagene autoleucel Ciltacabtagene autoleucel Teclistamab, Talquetamab Elranatamab, Linvoseltamab

Maintenance

Relapsed

Post Consolidation

Rescue

Daratumumab?

Carfilzomib?

Lenalidomide + PI

ASCT, autologous stem cell transplant; CAR, chimeric antigen receptor; Cy, cyclophosphamide; d- daratumumab; D/dex, dexamethasone; isa, isatuximab; K, carfilzomib; M, melphalan; PD-L1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib.

Speaker’s own opinions.

CAR T Cell Therapy Anito-cel Bispecific/Tri-specific Cevostomab Antibodies Iberdomide, Cell Modifying Agents Mezigdomide Venetoclax Sonrotoclax PD/PDL-1 Inhibition?

Small Molecules

* These agents are currently off the market but available through special programs

Second/Expert Opinion • You have the right to get a second opinion.

Insurance providers may require second opinions.

• A second opinion can help you: – Confirm your diagnosis – Give you more information about options – Talk to other experts – Introduce you to clinical trials – Help you learn which health care team you’d like to work with, and which facility

Where can I learn more?

Myeloma.org

Thank you https://seer.cancer.gov/statfacts/html/mulmy.html; dated 6.15.2024

Closing the Gap: Health Disparities in Myeloma (Video) Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO Chief Medical Officer, International Myeloma Foundation

Advancing Treatment Options Through Clinical Trials Andrew Yee, MD Massachusetts General Hospital, Boston, MA

Clinical Trials Andrew J. Yee, MD Clinical Director, Center for Multiple Myeloma Massachusetts General Hospital Cancer Center Assistant Professor of Medicine Harvard Medical School Waltham, MA September 2025

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Clinical Trials - Overview Some Of The Important Principles Of Clinical Trials: 

The drive of research has brought us to where we are



No one is expected to be a “guinea pig” with no potential benefit to them



Research is under very tight supervision and standards



Open, clear communication between the physician and the patient is fundamental

Driving research forward!

Clinical Trials: Myths MYTH: If I participate in a clinical trial, I might get a placebo, not active treatment MYTH: If I participate in a clinical trial, I can’t change my mind

• Phase 1 and 2, everyone gets active treatment • Phase 3 standard of care vs new regimen: often standard regimen with/without additional agent in MM trials • Patients can withdraw their consent for clinical trial participation at any time

MYTH: Clinical trials are dangerous because they have new medicines and practices

• Some risk is involved with every treatment, but medicines are used in clinical trials with people only after they have gone through testing to indicate that the drug is likely to be safe and effective for human use

MYTH: Clinical trials are expensive and not covered by insurance

• Research costs are typically covered by the sponsoring company • Standard patient care costs are typically covered by insurance • Check with clinical trial team/insurers; costs such as transportation, hotel, etc. may not be reimbursed and are paid by patient

PhRMA website. Accessed March 25, 2024. https://phrma.org/-/media/Project/PhRMA/PhRMA-Org/PhRMA-Org/PDF/A-C/CLINICAL-TRIALS-MYTH-FACT-PRINT.pdf?hsCtaTracking=f6689b95-1626-40d9-8c87-c6b 8d31600a4%7C35221aa8-d487-4db3-9416-b9c3c35e3bac .

Overview of New Drug Development

Identify a target for therapy in the laboratory

Confirm the anticancer activity in laboratory and animal studies

Clinical trials (human studies) to determine safety, dosing and effectiveness

The whole process costs millions of dollars and years of effort!

Preclinical

Clinical Trial Phases

PRECLINICAL STUDIES: Examine safety and potential for efficacy in the laboratory, in animal models

PHASE 1

PHASE 2

FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS

• Determine metabolism and pharmacokinetic, pharmacodynamics, maximum tolerate dose, and dose limiting toxicities, identify adverse events • Gain early evidence of efficacy, studied in many conditions; determine best dose (recommended phase 2 dose) to use in larger studies; typically, 20 to 80 patients • Everyone gets the investigational drug

EVALUATION OF EFFECTIVENESS IN A CERTAIN TUMOR TYPE • Determine efficacy at a given dose; everyone gets the investigational drug • Determine short-term adverse events and risks • Includes up to 100 patients, typically

PHASE 3

PHASE 4

COMPARED TO STANDARD OF CARE • • • •

Standard of care is not a placebo in oncology!

Hundreds to several thousand patients Often multiple institutions Sometimes treatment is blinded

APPROVED AGENTS IN NEW POPULATIONS OR NEW DOSE FORMS Faiman B, et al. Adv Pract Oncol. 2016;7:17-29.

Clinical Trials – Why Me?? 



Benefits of trials are numerous and include: 

Early access to “new” therapy



Contribution to myeloma world – present and future



Closer connection with your myeloma team

Must be balanced with potential risks 

“Toxicity” of side effects



Possibility of lack of efficacy



More testing to establish efficacy and monitoring



Treatments and monitoring all done (generally) at site of clinical trial

Why Do So Few Cancer Patients Participate in Trials?

Patients may:

• • • • •

Treating team may not be participating in clinical trials Be unaware of clinical trials Have practical and logistical barriers Face insurance or cost problems Fear, distrust, or be suspicious of research

54

Importance of Clinical Trial Participation

by Diverse Populations

“

[P]eople from racial and ethnic minorities and other diverse groups are underrepresented in clinical research. This is a concern because people of different ages, races, and ethnicities may react differently to certain medical products.

– FDA

Leadership and commitment Community engagement practices

Investigator hiring, training, and mentoring practices

Patient engagement practices

US Cancer Centers of Excellence: Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials

FDA = US Food and Drug Administration. Regnante JM, et al. J Oncol Pract. 2019;15(4):e289-e299. FDA website. Clinical Trial Diversity. Accessed March 27, 2024. https://www.fda.gov/consumers/minority-health-and-health-equity/clinical-trial-diversity.

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Is A Clinical Trial Right For Me? Discuss with your physician if you are eligible for a clinical trial Clinical trials have eligibility criteria that generally require “measurable disease,” adequate blood counts, kidney function, etc.

Work with your physician to determine the best trial for you Meet with the clinical research nurse or trials coordinator to discuss the trial Carefully review the provided “Informed Consent” Describes the study and any potential safety concerns related to the experimental medication

Commonly Asked Questions How does the study work? How often will I need to see my doctor or visit the cancer center?

Will I need to undergo additional tests?

What is currently known about the new drug or combination?

What benefits can I expect?

What side effects should I expect? Who should I notify if I have side effects?

Can I take my vitamins or other medications?

Can I get the treatment with my local doctor?

Will my insurance pay for my participation in the clinical trial?

IMF Infoline

Resources to Find Clinical Trials and Avoid Bias

US & Canada: 800-452 CURE (2873) Worldwide: 1-818-487-7455 infoline@myeloma.org Clinicaltrials.gov https://clinicaltrials.gov/

Just ASKTM Implicit Bias Training from Association of Community Cancer Centers website. Accessed March 15, 2024. https://www.accc-cancer.org/home/attend/webi nar-template/2022/07/25/on-demand/just-ask-i ncreasing-diversity-in-cancer-clinical-research

58

Let’s Get Social:

Myeloma.org

Q&A WITH PANEL

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70

BREAK

WHEN YOU RETURN FROM BREAK PLEASE HEAD TO YOUR SELECTED BREAKOUT SESSION: BREAKOUT A: NDMM - GETTING STARTED WITH MYELOMA MANAGEMENT Dr. Shonali Midha, MD Please move to Hastings II Room BREAKOUT B: RRMM - CONTINUING THE MYELOMA TREATMENT JOURNEY Dr. Andrew Yee, MD Please remain in this room

Thank you to our speakers & our sponsors!

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

72

Frontline Therapy Shonali Midha, MD Dana-Farber Cancer Institute ,Boston, MA

74

Objectives  Review the importance of DEPTH of response in early treatment of

myeloma and the increasing use of MRD testing

 Discuss emerging approaches in transplant eligible patients, including

quadruplet therapy and stem cell transplantation

 Outline the approach to a patient not going to transplant and how to

optimize therapy

Goals of Therapy: The Iceberg Model of Myeloma

Disease Burden (# of myeloma cells)

Treatment

>1 Trillion

Symptomatic Myeloma At diagnosis Partial response 50% reduction in M protein

>1 Billion

>10 Million 1 myeloma cell in 100K to 1 million normal cells

Very good partial response 90% reduction in M protein immunofixation positive only Complete remission No M-protein immunofixation negative Minimal Residual Dis Flow Cytometry Minimal Residual Dis Next Generation Molecular testing

Depth of response matters!

MRD refers to the persistence of residual tumor cells after treatment and is responsible for relapse1

Current techniques can detect MRD with a sensitivity of 10-6 for MM cells2

TUMOR LOAD

R0

R1

DE P R2

R3 MR→PR→ VGPR→CR →sCR

10–2

MRDhigh MRDlow

10–6

MRDpos

MRDneg Induction

Consolidation

Maintenance

Preemptive

TIME MINIMAL RESIDUAL DISEASE DETECTION MR, minimal response; neg, negative; pos, positive; R, relapse

1. Adapted from Hauwel M, Matthes T. Swiss Med Wkly 2014:144:w13907 2. Biran N, et al. Curr Hematol Malig Rep 2014;9:368–78

TH

MRD is Prognostic – Both for PFS and OS

Lahuerta JJ, Paiva B, et al. J Clin Oncol. 2017; 35(25): 2900–2910

SMOLDERING MULTIPLE MYELOMA

What about Smoldering Myeloma?

• Recall that all patients prior to having active myeloma, have MGUS (monoclonal gammopathy of undetermined significance) then SMM (smoldering myeloma) • Historically we have not treated smoldering myeloma, but redefined MM to include “ultra-high risk smoldering myeloma” • But now clinical trials are being conducted in patients with smoldering myeloma – mostly “high risk” • High risk SMM is defined in different ways, often including at least 2 out of 3 of the following factors: • M spike 2 or more • Light chain ratio (involved/uninvolved) 20 or over • Bone Marrow Plasmacytosis of 20% or higher

Phase 3 Randomized Study of Daratumumab Monotherapy Versus Active Monitoring in Patients With High-risk Smoldering Multiple Myeloma: Primary Results of the AQUILA Study Meletios A Dimopoulos1, Peter M Voorhees 2, Fredrik Schjesvold 3, Yael C Cohen4, Vania Hungria5, Irwindeep Sandhu6, Jindriska Lindsay 7, Ross I Baker8, Kenshi Suzuki9, Hiroshi Kosugi10, Mark-David Levin11, Meral Beksac 12, Keith Stockerl-Goldstein 13, Albert Oriol14, Gabor Mikala15, Gonzalo Garate16, Koen Theunissen17, Ivan Spicka18, Anne K Mylin19, Sara Bringhen20, Katarina Uttervall21, Bartosz Pula22, Eva Medvedova23, Andrew J Cowan24, Philippe Moreau25, Maria-Victoria Mateos26, Hartmut Goldschmidt27, Tahamtan Ahmadi28, Linlin Sha29, Els Rousseau30, Liang Li29, Robyn M Dennis31, Robin Carson32, S Vincent Rajkumar33 National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece; 2Levine Cancer Institute, Atrium Health Wake Forest University School of Medicine, Charlotte, NC, USA; 3Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway; 4Tel-Aviv Sourasky (Ichilov) Medical Center and Tel Aviv University, Tel Aviv, Israel; 5Clínica Medica São Germano, São Paulo, Brazil; 6Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; 7Kent and Canterbury Hospital, Kent, UK; 8Perth Blood Institute, Murdoch University, Perth, Australia; 9Japanese Red Cross Medical Center, Tokyo, Japan; 10Ogaki Municipal Hospital, Ogaki City, Japan; 11Albert Schweitzer Hospital, Dordrecht, The Netherlands; 12Ankara University, Ankara, Turkey; 13Washington University School of Medicine, St. Louis, MO, USA; 14Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias I Pujol, Barcelona, Spain; 15South-Pest Central Hospital, National Institute for Hematology and Infectious Diseases, Budapest, Hungary; 16Hospital Alemán, Buenos Aires, Argentina; 17Jessa Hospital, Hasselt, Belgium; 18Charles University and General Hospital, Prague, Czech Republic; 19Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 20SSD Clinical Trials in Oncol-ematologia e Mieloma Multiplo, AOU Città della Salute e della Scienza di Torino, Torino, Italy; 21Medical Unit Hematology, Karolinska University Hospital, Stockholm, Sweden; 22Institute of Hematology and Transfusion Medicine, Warszawa, Poland; 23Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA; 24University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA; 25University Hospital Hôtel-Dieu, Nantes, France; 26University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain; 27GMMG Study Group at University Hospital Heidelberg, Internal Medicine V, Heidelberg, Germany; 28Genmab US Inc., Plainsboro, NJ, USA; 29Janssen Research & Development, LLC, Shanghai, China; 30Janssen Research & Development, Beerse, Belgium; 31 Janssen Research & Development, LLC, Raritan, NJ, USA; 32Janssen Research & Development, LLC, Spring House, PA, USA; 33Mayo Clinic, Rochester, MN, USA. 1

Presented by MA Dimopoulos at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA

https://www.congresshub.com/ASH2024/ Oncology/Daratumumab/Dimopoulos The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way.

AQUILA: Study Design AQUILA enrollment period: December 2017 to May 2019 at 124 sites in 23 countries Treatment/active monitoring phase

Key eligibility criteria: • ≥18 years of age • Confirmed SMM diagnosis (per IMWG criteria) for ≤5 years • ECOG PS score of 0 or 1 • Clonal BMPCs ≥10% and ≥1 of the following risk factors: - Serum M-protein ≥30 g/L - IgA SMM - Immunoparesis with reduction of 2 uninvolved Ig isotypes - Serum involved:uninvolved FLC ratio ≥8 and <100 - Clonal BMPCs >50% to <60%

DARA monotherapy

All patients were required to have CT/PET-CT and MRI imaging during screening

1:1 randomization (N = 390)

Screening

1800 mg SCb QW Cycles 1-2, Q2W Cycles 3-6, Q4W thereafter in 28-day cycles until 39 cycles/36 months*

Active monitoring No disease-specific treatment, with AE monitoring up to 36 months*

Follow-up phase • Efficacy follow-up until progression

by SLiM-CRAB • Survival follow-up every 6 months until end of study

Primary endpoint: • PFS by IRC per IMWG SLiM-CRAB criteriac Key secondary endpoints: • ORR • Time to first-line treatment for MM • PFS on first-line treatment for MM • Overall survival

*Or confirmed disease progression (whichever occurred first).

Stratified by number of risk factorsa for progression to MM (<3 vs ≥3)

Disease evaluation schedule • Laboratory efficacy – Every 12 weeks by central lab until disease progression • Imaging (CT/PET-CT, MRI) – Yearly (central review) • Bone marrow – At least every 2 years

IMWG, International Myeloma Working Group; ECOG PS, Eastern Cooperative Oncology Group performance status; BMPC, bone marrow plasma cell; FLC, free light chain; CT, computed tomography; MRI, magnetic resonance imaging; QW, weekly; Q2W, every 2 weeks; Q4W, every 4 weeks; AE, adverse event; IRC, independent review committee; ORR, overall response rate. aRisk factors included involved:uninvolved FLC ratio 8 (yes vs no), serum M-protein 30 g/L (yes vs no), IgA SMM (yes vs no), immunoparesis (reduction of 2 uninvolved immunoglobulins vs other), or clonal BMPCs (>50% to <60% vs 50%). bDARA SC (1800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE ® drug delivery technology; Halozyme, Inc.]). cPFS was defined as duration from randomization to initial documented progression to active MM or death due to any cause, whichever occurred first.

Presented by MA Dimopoulos at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA

82

AQUILA: Progression to MM by IMWG SLiM-CRAB Criteria (IRC Assessment) 100

Percentage of patients surviving without disease progression

DARA (n = 194)

Active monitoring (n = 196)

67 (34.5)

99 (50.5)

Death without disease progression

5 (2.6)

5 (2.6)

Disease progressiona

62 (32.0)

94 (48.0)

CRAB criteria

12 (6.2)

34 (17.3)

Calcium elevation

0

2 (1.0)

Renal insufficiencyb

0

0

Anemia

2 (1.0)

14 (7.1)

Bone disease

10 (5.2)

18 (9.2)

50 (25.8)

65 (33.2)

Clonal BMPCs

5 (2.6)

16 (8.2)

Serum FLC

33 (17.0)

33 (16.8)

Focal lesion by MRI

12 (6.2)

16 (8.2)

Median follow-up: 65.2 months 79.9%

80

63.3%

60

Daratumumab Median: not reached 63.1%

40

HR, 0.49 (95% CI, 0.36-0.67) P <0.001

20

Active monitoring Median: 41.5 months

40.8%

SLiM criteria

DARA treatment 0 0

3

6

9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72

Months since randomization

No. at risk Daratumumab 194 188 181 179 166 156 149 145 142 139 138 135 129 121 118 114 106 102 99 96 90 67 41 17 Active monitoring 196 180 175 160 142 131 120 111 100 91 87 83 78 71 67 65 60 55 51 50 49 33 19 8

PFS event, n (%)

6 2

DARA significantly reduced the risk of progression to MM or death by 51% versus active monitoring; the benefit continued beyond 36 months HR, hazard ratio; CI, confidence interval. aA patient may show disease progression based on ≥1 criterion. bSome patients met the CRAB criteria for renal insufficiency, but the investigator attributed this to a cause other than disease progression to MM. Adapted with permission © The New England Journal of Medicine (2024).

Presented by MA Dimopoulos at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA

83

Percentage of patients surviving

AQUILA: Overall Survival 100

93.0%

80

86.9% Active monitoring

Daratumumab

60

40

DARA (n = 194)

Active monitoring (n = 196)

15 (7.7)

26 (13.3)

Disease progression

3

9

AE

2

4

Other*

10

13

Deaths, n (%) Primary cause, n

20

HR, 0.52 (95% CI, 0.27-0.98)

0 0

3

6

9

12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 Months since randomization

No. at risk Daratumumab 194 194 194 193 192 191 188 188 188 188 188 186 184 179 177 176 175 174 172 169 162 128 86 38 11 Active monitoring 196 192 191 191 187 183 179 177 176 173 169 168 165 164 159 155 155 154 153 149 144 108 68 34 9

*Deaths due to an event occurring after the AE reporting window (ie, events that happened after patient started subsequent therapy or >30 days after last dose) or deaths with unknown reason.

Early intervention with fixed duration DARA extended overall survival versus active monitoring Adapted with permission © The New England Journal of Medicine (2024).

Presented by MA Dimopoulos at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA

84

AQUILA: Safety Overview Event, n (%)

DARA (n = 193)

Active monitoring (n = 196)

DARA (n = 193)

Active monitoring (n = 196)

Median duration of AE reporting

35 months

26 months 162 (82.7)

Treatment discontinuations due to a TEAEb

Any grade TEAEs

187 (96.9)

11 (5.7)

–

Grade 3 or 4 TEAEs

78 (40.4)

59 (30.1)

Dose modifications due to a TEAEc

90 (46.6)

–

COVID-19 TEAEs

17 (8.8)

10 (5.1)

Serious COVID-19 TEAEs

5 (2.6)

1 (0.5)

Deaths due to COVID-19

2 (1.0)

0

Most common grade 3 or 4 TEAEs (≥5% in either group) Hypertension Serious TEAEs

11 (5.7)

9 (4.6)

56 (29.0)

38 (19.4)

Most common serious TEAEs (≥2% in either group) Pneumonia

7 (3.6)

1 (0.5)

Grade 5 TEAEsa

2 (1.0)

4 (2.0)

Event, n (%)

Low rate of DARA discontinuation due to TEAEs, and no new safety concerns were identified TEAE, treatment-emergent adverse event. TEAEs include all AEs occurring during the 36-month treatment/monitoring phase or for 30 days after discontinuation of DARA or active monitoring, or until the start of subsequent treatment for MM. aGrade 5 TEAEs included COVID-19 infection and COVID-19 pneumonia in the DARA group and pulmonary edema, cardiac arrest, pulmonary embolism, and cardiac failure in the active monitoring group. b The most frequently reported TEAEs leading to DARA discontinuation were fatigue, dyspnea, and anxiety (n = 2 each). cDose modifications include dose delays within a cycle, cycle delays, and skipped doses.

Presented by MA Dimopoulos at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition; December 7-10, 2024; San Diego, CA, USA

85

Points for Smoldering Myeloma

• • • •

Wow this is a VERY important study and may well change the way we think about and treat high risk smoldering myeloma The study was critical to really prove we can delay the progression to active myeloma and even improve survival with 3 years of daratumumab It underscores the importance of a DISCUSSION with the healthcare team as many options can be offered to patients with high-risk smoldering MM There will be MANY more trials coming in this area, with even more intense therapies like combinations and even CAR T Cell therapy...

NEWLY DIAGNOSED MULTIPLE MYELOMA

Personalized Approach to Frontline Therapy

Newly Diagnosed MM and Risk Stratified Factors to be considered for ASCT

Age, performance status (PS), comorbidities (R-MCI score, HCT-Cl) and organ function

ASCT Eligible

ASCT Ineligible

General Principles of Initial Therapy 1. Most patients will be given a combination of drugs to control the disease quickly, usually a QUADRUPLET 2. We don’t “save the best for last” because early therapies have a long term effect on survival 3. We seek a DEEP and DURABLE response 4. We mix and match from the 3 major classes of drugs and add steroids: Proteasome Inhibitors – most often botezomib (Velcade) Immunomodulatory Drugs – lenalidomide (Revlimid) Monoclonal Antibodies – daratumumab (Darzalex) and Isatuximab (Sarclisa) 5. We decide early on whether or not someone will have a stem cell

THIS JUST IN!!

QUADRUPLET therapies are becoming the standard of care for MOST (but not all) patients with newly diagnosed MM DVRD and Isa-VRD combinations below now FDA approved Transplant Eligible Darzalex-Velcade-Revlimid-Dexamethasone (PERSEUS) Transplant Ineligible Sarclisa-Velcade-Revlimid-Dexamethasone (IMROZ) Sarclisa-Velcade-Revlimid-Dexamethasone (BENEFIT) Darzalex-Velcade-Revlimid-Dexamethasone (CEPHEUS)

• Transplanteligible NDMM • Age 18-70 years • ECOG PS ≤2

Induction

Consolidation

VRd

VRd

V: 1.3 mg/m SC Days 1, 4, 8, 11 R: 25 mg PO Days 1-21 d: 40 mg PO/IV Days 1-4, 9-12 2

D-VRd

DARA: 1,800 mg SC QW Cycles 1-2 Q2W Cycles 3-4

b

VRd administered as in the VRd group 4 cycles of 28 days

TRANSPLANT

Key eligibility criteria:

1:1 Randomization (N = 709)a

PERSEUS: Study Design

V: 1.3 mg/m2 SC Days 1, 4, 8, 11 R: 25 mg PO Days 1-21 d: 40 mg PO/IV Days 1-4, 9-12

D-VRd

DARA: 1,800 mg SC Q2W b

VRd administered as in the VRd group

2 cycles of 28 days

Primary endpoint: PFSc Key secondary endpoints: Overall CR rate,c overall MRD-negativity rate,d OS

Maintenance

R

R 10 mg PO Days 1-28 until PD

D-R

DARA: 1,800 mg SCb Q4W R: 10 mg PO Days 1-28

MRD positive

Continue D-R until PD

MRD negativ e

Discontinue DARA therapy only

28-day cycles

Discontinue DARA therapy only after 24 months of D-R maintenance for patients with CR and 12 months of sustained MRD negativity

Restart DARA therapy upon confirmed loss of CR without PD or recurrence of MRD

ECOG PS, Eastern Cooperative Oncology Group performance status; V, bortezomib; SC, subcutaneous; PO, oral; d, dexamethasone; IV, intravenous; QW, weekly; Q2W, every 2 weeks; PD, progressive disease; Q4W, every 4 weeks; MRD, minimal residual disease; CR, complete response; OS, overall survival; ISS, International Staging System; rHuPH20, recombinant human hyaluronidase PH20; IMWG, International Myeloma Working Group; VGPR, very good partial response. aStratified by ISS stage and cytogenetic risk. bDARA 1,800 mg co-formulated with rHuPH20 (2,000 U/mL; ENHANZE  drug delivery technology, Halozyme, Inc., San Diego, CA, USA). cResponse and disease progression were assessed using a computerized algorithm based on IMWG response criteria. dMRD was assessed using the clonoSEQ assay (v.2.0; Adaptive Biotechnologies, Seattle, WA, USA) in patients with VGPR post consolidation and at the time of suspected CR. Overall MRD-negativity rate was defined as the proportion of patients who achieved both MRD negativity (10 –5 threshold) and CR at any time.

Presented by P Sonneveld at American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, CA, USA.

91

PERSEUS: Progression-free Survival % surviving without progression

Median follow-up: 47.5 months

48-month PFS

100

84.3%

80

67.7%

60

D-VRd VRd

40 20

HR, 0.42; 95% CI, 0.30-0.59; P <0.0001

0

0

3

6

9

12

15

18

21

24

No. at risk VRd 354 D-VRd 355

335 345

321 335

311 329

304 327

297 322

291 318

283 316

278 313

27 30 Months 270 309

258 305

33

36

39

42

45

48

51

54

247 302

238 299

228 295

219 286

175 226

67 90

13 11

0 0

58% reduction in the risk of progression or death in patients receiving D-VRd

HR, hazard ratio; CI, confidence interval.

Presented by P Sonneveld at American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, CA, USA.

92

PERSEUS: Overall CR Rates

100 90

Response rate, %

80

P <0.0001 Odds ratio, 3.13 (95% CI, 2.11-4.65)

Subgroup

≥CR 87.9%

≥CR 70.1%

70 60 50

VRd

69.3

44.6

40

sCR

30

CR

20 10 0

25.4

18.6

D-VRd (n = 355)

VRd (n = 354)

D-VRd

Odds ratio (95% CI)

no. of patients with ≥CR/total no. (%)

Sex Male 143/205 (69.8) Female 105/149 (70.5) Age <65 years 186/267 (69.7) ≥65 years 62/87 (71.3) Race White 226/323 (70.0) Other 22/31 (71.0) ISS stage I 129/178 (72.5) II 84/125 (67.2) III 34/50 (68.0) Type of MM lgG 122/185 (65.9) Non-lgG 73/96 (76.0) Cytogenetic risk Standard risk 182/266 (68.4) High risk 59/78 (75.6) Indeterminate 7/10 (70.0) ECOG performance status 0 160/230 (69.6) ≥1 88/124 (71.0)

185/211 (87.7) 127/144 (88.2)

3.08 (1.86-5.12) 3.13 (1.69-5.80)

235/261 (90.0) 77/94 (81.9)

3.94 (2.43-6.37) 1.83 (0.91-3.68)

289/330 (87.6) 23/25 (92.0)

3.03 (2.02-4.53) 4.70 (0.91-24.25)

167/186 (89.8) 101/114 (88.6) 44/55 (80.0)

3.34 (1.87-5.95) 3.79 (1.91-7.54) 1.88 (0.77-4.58)

178/204 (87.3) 72/78 (92.3)

3.54 (2.12-5.90) 3.78 (1.45-9.83)

234/264 (88.6) 63/76 (82.9) 15/15 (100)

3.60 (2.27-5.70) 1.56 (0.71-3.44) NE (NE-NE)

195/221 (88.2) 117/134 (87.3)

3.28 (2.00-5.39) 2.82 (1.49-5.34)

0.1

1

10

Favors VRd Favors D-VRd

• Overall CR rate was significantly higher with D-VRd versus VRd • CR rate was improved with D-VRd versus VRd across subgroups P value (2-sided) was calculated with the use of the stratified Cochran–Mantel–Haenszel chi-squared test.

Presented by P Sonneveld at American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, CA, USA.

93

Phase 3 Study Results of Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRd) Versus VRd for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma (IMROZ) Thierry Facon,1 Meletios-Athanasios Dimopoulos,2 Xavier Leleu,3 Meral Beksac,4,5 Ludek Pour,6 Roman Hajek,7 Zhuogang Liu,8 Jiri Minarik,9 Philippe Moreau,10 Joanna Romejko-Jarosinska,11 Ivan Spicka,12 Vladimir Vorobyev,13 Michele Cavo,14 Hartmut Goldschmidt,15 Thomas Martin,16 Salomon Manier,17 Marie-France Brégeault,18 Sandrine Macé,18 Christelle Berthou,18 Robert Z. Orlowski19 Department of Haematology, University of Lille, and French Academy of Medicine, Paris, France; 2Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece; Service d'Hématologie et Thérapie Cellulaire, CHU and CIC Inserm 1402, Poitiers Cedex, France; 4Department of Hematology, Ankara University, Ankara, Turkey; 5Istinye University Ankara Liv Hospital, Ankara, Turkey; 6Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic; 7Department of Hemato-Oncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; 8Shengjing Hospital of China Medical University (Huaxiang Br), Shenyang, China; 9Department of HematoOncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, Olomouc, Czech Republic; 10Department of Hematology, University Hospital HôtelDieu, Nantes, France; 11Department of Lymphoid Malignancies, Marie Sklowdoska-Curie National Research Institute of Oncology, Warszawa, Poland; 12Charles University and General Hospital in Prague, Prague, Czech Republic; 13SP Botkin Moscow City Clinical Hospital, Moscow, Russia; 14IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli," Università di Bologna, Bologna, Italy; 15Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany; 16Department of Hematology, University of California at San Francisco, San Francisco, California, USA; 17Department of Hematology, University Hospital Center of Lille, Lille, France; 18Sanofi, R&D, Vitry-sur-Seine, France; 19Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 1

3

Presentation at the 21st International Myeloma Society Annual Meeting | September 25–28, 2024

ID #OA-49

Copies of this presentation obtained through Quick Response (QR) Code are for personal use only

Ti* NDMM ≤80 years N=446

Randomization 3:2

Study design: Isa-VRd vs VRd in transplant-ineligible NDMM Initiation phase (4 x 6-week cycles) Isa + VRd

Isa + Rd

VRd

Day Initiation phase

Treatment until PD, unacceptable toxicities, patient withdrawal

PD†

MRD (bone marrow aspirate)  In case of CR or VGPR Isa IV (C1 only)

10 mg/kg

Isa IV (C2–4)

10 mg/kg

V SC

1.3 mg/m2

R PO‡

25 mg

d IV/PO§

20 mg

Day Maintenance phase

Maintenance phase (4-week cycles)

Isa IV (C5–17)

10 mg/kg

Isa IV (C18+)

10 mg/kg

R PO‡

25 mg

d IV/PO

20 mg

Rd





At end of initiation phase

12 mo



18 mo



24 mo

Primary endpoint: PFS Key secondary endpoints: CR rate, MRD– CR (NGS, 10-5) rate, ≥VGPR rate, OS



36 mo

1

8

15

22

29

1

8

15

22

29

36

43

*Patients considered Ti due to age or comorbidities. † In the maintenance phase, patients randomized to the VRd arm who experience PD may cross over to receive Isa-Rd. ‡ 10 mg/day if eGFR 30 to <60 mL/min/1.73 m2. § If aged ≥75 years, d was administered on days 1, 4, 8, 11, 15, 22, 25, 29, and 32.

C, cycle; CR, complete response; d, dexamethasone; eGFR, estimated glomerular filtration rate; Isa, isatuximab; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; NGS, next-generation sequencing; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PO, orally; R, lenalidomide; SC, subcutaneous; Ti, treatment-ineligible; V, bortezomib; VGPR, very good partial response.

Orlowski RZ, et al. ASCO 2018.

95

Baseline characteristics ITT population Age, median (range), years

Isa-VRd (n=265)

VRd (n=181)

72.0 (60–80)

72.0 (55–80)

Age by category, years, n (%)

Isa-VRd (n=265)

VRd (n=181)

I or II

234 (88.3)

157 (86.7)

ITT population R-ISS stage (IRT strata), n (%)

<65

8 (3.0)

9 (5.0)

III

29 (10.9)

21 (11.6)

65 to <70

73 (27.5)

47 (26.0)

Not classified

2 (0.8)

3 (1.7)

70 to <75

115 (43.4)

68 (37.6)

Cytogenetic risk, n (%)

75 to 80

69 (26.0)

57 (31.5)

Standard

207 (78.1)

140 (77.3)

High†

40 (15.1)

34 (18.8)

High and 1q21+‡

19 (7.2)

15 (8.3)

1q21+/amplification 1q21,§ n (%)

95 (35.8)/ 32 (12.1)

70 (38.7)/ 23 (12.7)

Del(17p) (50% cutoff), n (%)

15 (5.7)

9 (5.0)

Extramedullary disease at study entry¶ (per IRC), n (%)

18 (6.8)

6 (3.3)

ECOG PS, n (%) 0

123 (46.4)

79 (43.6)

1

112 (42.3)

83 (45.9)

2*

29 (10.9)

19 (10.5)

66 (24.9)

62 (34.3)

eGFR <60 mL/min/1.73 m² (MDRD), n (%)

Patient characteristics were balanced in both arms *One patient in the Isa-VRd arm had an ECOG PS of 3. †High risk defined as the presence of del(17p) and/or t(4;14) and/or t(14;16), with cutoffs defined in footnote ‡. ‡Abnormality defined as present in at least 30% of abnormal bone marrow plasma cells for t(4;14) and t(14;16) and 1q21+ (at least 3 copies), and at least 50% of abnormal plasma cells for del(17p). Only one patient had 2 high-risk cytogenetic abnormalities: del(17p) and t(4;14). §1q21+ defined as at least 3 copies of 1q21. Amplification 1q21 defined as at least 4 copies of 1q21. ¶In addition, there were 67 (25.3%; Isa-VRd) and 49 (27.1%; VRd) patients with paramedullary disease and 1 patient in each group with both extramedullary and paramedullary disease.

ECOG PS, Eastern Cooperative Oncology Group Performance Status; eGFR, estimated glomerular filtration rate; IRC, independent review committee; IRT, interactive response technology; 96 ITT, intent-to-treat; MDRD, Modification of Diet in Renal Disease; R-ISS, Revised International Staging System; VRd, bortezomib, lenalidomide and dexamethasone.

Primary endpoint met: Interim PFS analysis–IRC assessment in ITT population

Kaplan–Meier estimate

162 PFS events: 84 (31.7%) in Isa-VRd; 78 (43.1%) in VRd*

1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0

Number at risk

Isa-VRd VRd

60-mo PFS rate: 63.2% mPFS: NR

HR, 0.596 (98.5% CI, 0.406–0.876)

Isa-VRd VRd Censor

60-mo PFS rate: 45.2% mPFS: 54.34 months (95% CI, 45.207 to NR)

Log-rank P=0.0005†

0

6

12

18

24

30 36 42 Time, months

48

54

60

66

72

265 181

243 155

234 141

217 121

201 104

190 96

153 70

104 51

43 20

2 2

0 0

177 89

164 81

At a median follow-up of 5 years (59.7 months), Isa-VRd followed by Isa-Rd led to a statistically significant reduction in the risk of progression or death by 40.4% *Cutoff date for PFS analysis: September 26, 2023 (median follow-up, ~5 years). †Nominal one-sided P value.

CI, confidence interval; HR, hazard ratio; Isa, isatuximab; ITT, intent-to-treat; mPFS, median PFS; NR, not reached; PFS, progression-free survival; Rd, lenalidomide and dexamethasone; VRd, bortezomib, lenalidomide and dexamethasone.

Facon T, Dimopoulos MA, Leleu X, et al. Isatuximab, Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma. New England Journal of Medicine 2024. NEJM ms 24-00712, Reprinted with permission from Massachusetts Medical Society.

97

BENEFIT Study design: Isa-VRd vs Isa-Rd in Ti NDMM

Cycle 1 only. CR, complete response; Cy, cycle; d, dexamethasone; D, day; Isa, isatuximab; M, month; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; NGS, next generation sequencing; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; R, lenalidomide; SPM, second primary malignancy; Ti, transplant-ineligible; V, bortezomib; VGPR, very good partial response. †

PRESENTED BY:

Xavier Leleu, MD, PhD

Quadruplet Frontline Summary Quadruplets are indeed better than triplets in patients going to transplant They also seem to be better in transplant ineligible patients but with some caveats

we have less evidence in patients over 80 dosing of drugs is CRITICAL to ensure tolerability Revlimid – we don’t need 25mg in most patients Velcade – should be given weekly – still unclear as to length of time Dexamethasone – DOWN with DEX! – we can taper and discontinue in the first 4-6 months

Darzalex-VRD for transplant eligible and Sarclisa-VRD for transplant ineligible now FDA approved!

#DownWithDex HISTORICAL TREND TOWARD OPTIMAL DEXAMETHASONE DOSING High Dose Dexamethasone

Low Dose Dexamethasone

“Lower” Dose Dexamethasone

40 mg x 12 days per month x 6 months

40 mg x 4 days per month x 6 months

Optimal dose yet to be defined

Harding and Mikhael, Blood Editorial “Down with dex!” 2025

DO WE REALLY STILL NEED TRANSPLANT??

RVD +Stem Cell Transplant vs. RVD without Transplant DETERMINATION Trial of Newly Diagnosed MM:

DESIGN

-Patients aged 18-65 yrs with symptomatic newly diagnosed MM following 1 cycle of RVD -56 sites within the United States from 2010 to 2018

RVD cycles 2-3 (n = 357) RVD cycles 2-3 (n = 365)

Stem cell collection

Induction

ASCT: Melphalan 200 mg/m2 + Stem Cell Support (n = 310)

Consolidation

Maintenance Until Progression

RVD cycles 4-8

R (n = 291)

RVD cycles 4-5

R (n = 289)

End Points of Study and Follow-up

• Primary end point: progression-free survival (time to next relapse) • Secondary end points included: • Response rates, overall survival, quality of life, and adverse events

• Follow-up on participant status : median of 6 years N Engl J Med. 2022 Jul 14;387(2):132-147. doi: 10.1056/NEJMoa2204925

Slide credit: clinicaloptions.com

Primary endpoint: Progression-free survival (PFS)

Events – no. (%)

Median PFS, months (95% CI)

5-year PFS, % (95% CI)

RVd-alone

189 (52.9%)

46.2 (38.1–53.7)

41.5 (35.7–47.2)

RVd+ASCT

139 (38.1%)

67.5 (58.6–NR)

55.6 (49.4–61.3)

HR 1.53 (1.23–1.91), p<0.0001

Paul G. Richardson, MD

CI, confidence interval; HR, hazard ratio; Data cut off: 12/12/21

103

RVD +Stem Cell Transplant vs. RVD without Transplant DETERMINATION Trial of Newly Diagnosed MM

Quality of Life

Global Health Status/QoL,

Physical Functioning

N Engl J Med. 2022 Jul 14;387(2):132-147. doi: 10.1056/NEJMoa2204925

DETERMINATION Discussion ASCT remains very relevant and important in prolonging PFS in younger and eligible patients BUT it may not be mandatory in all eligible patients upfront 

As with other agents, we INDIVIDUALIZE the sequencing patterns

ASCT does carry genuine toxicity, short term and long term 

We may become callous to these toxicities

Maintenance therapy remains an important part of myeloma therapy Joseph Mikhael – ASCO Plenary Discussant DETERMINATION © 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

105

ASCO Guidelines: What criteria are used to assess eligibility for autologous stem cell transplant (SCT)?

Recommendation

Evidence Rating

Patients should be referred to a transplant center to determine transplant eligibility

Type: Evidence based Evidence quality: Intermediate, benefit outweighs harm Strength of recommendation: Moderate

Chronologic age and renal function should not be the sole criteria used to determine eligibility for SCT.

Type: Evidence based Evidence quality: Intermediate, benefit outweighs harm Strength of recommendation: Moderate

Mikhael J, et al. J Clin Oncol. April 1, 2019. DOI:10.1200/JCO.18.02096.

What about patients not eligible for transplant?

As noted before, quadruplets are now becoming the standard of care for most patients However, some patients may not be “quad eligible” In these patients, triplets, or even doublets may be considered the most commonly used regimen is DRD – darzalex, revlimid and dex this is based on the MAIA trial of DRD vs RD

MAIA Study Design – DRD vs RD ‒

Patients were enrolled in MAIA from March 2015 through January 2017

Key eligibility criteria • TIE NDMM • ECOG PS score 0-2 • CrCl ≥30 mL/min

1:1 randomisation

D-Rd

D: 16 mg/kg IV QW Cycles 1-2, Q2W Cycles 3-6, then Q4W thereafter until PD R: 25 mg PO Days 1-21 until PD da: 40 mgb PO or IV Days 1, 8, 15, 22 until PD

Rd

End-oftreatment visit (30 days after last dose)

Primary endpoint • PFS Longterm follow-up

R: 25 mg PO Days 1-21 until PD d: 40 mg PO Days 1, 8, 15, 22 until PD

Key secondary endpoints • OS • PFS2 • ORR • CR/sCR rate • MRD (NGS; 10–5)

Cycles: 28 days

MAIA is a multicentre, randomised, open-label, active-controlled, phase 3 study of D-Rd versus Rd alone in patients with NDMM who are transplant ineligible TIE, transplant-ineligible; ECOG PS, Eastern Cooperative Oncology Group performance status; CrCl, creatinine clearance; IV, intravenous; QW, once weekly; Q2W, once every 2 weeks; Q4W, once every 4 weeks; PD, progressive disease; PO, oral; ORR, overall response rate; CR, complete response; sCR, stringent complete response; MRD, minimal residual disease; NGS, next-generation sequencing; BMI, body mass index. a On days when DARA is administered, dexamethasone will be administered to patients in the D-Rd arm and will serve as the treatment dose of steroid for that day, as well as the required pre-infusion medication. bFor patients >75 years of age or with BMI <18.5 kg/m 2, dexamethasone was administered at a dose of 20 mg QW.

Updated PFS

60-month PFS rate

% surviving without progression

100 80 52.5%

60

D-Rd: median, NR

28.7%

40

Rd: median, 34.4 months 20 0

HR, 0.53; 95% CI, 0.43-0.66; P <0.0001 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 Months

No. at risk Rd 369 333 307 280 255 237 220 205 196 179 172 155 146 133 123 113 105 94 63 36 12 4 D-Rd 368 347 335 320 309 300 290 276 266 256 246 237 232 222 210 199 195 170 123 87 51 17

2 5

0 0

• D-Rd continued to demonstrate a significant PFS benefit, with median PFS not reached with D-Rd • These data provide a new PFS benchmark in patients with NDMM who are transplant ineligible NR, not reached; CI, confidence interval.

Overall Survival 60-month OS rate 100

% surviving

80

66.3% D-Rd: median, NR

53.1%

60

Rd: median, NR

40 20 0

HR, 0.68; 95% CI, 0.53-0.86; P = 0.0013 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 Months

No. at risk Rd 369 351 343 336 324 317 308 300 294 281 270 258 251 241 232 223 213 183 134 85 42 14 5 D-Rd 368 350 346 344 338 334 328 316 305 302 297 286 280 273 266 255 249 228 170 118 63 22 6

1 1

0 0

D-Rd demonstrated a significant benefit in OS, with a 32% reduction in the risk of death, in patients with NDMM who are transplant ineligible

Key Take-Aways Although historically we have not treated smoldering myeloma, new evidence suggests we can treat patients with high risk SMM with daratumumab monotherapy for 3 years D-VRD is the new standard of care in Transplant Eligible Patients Isa-VRD is a new standard of care in Transplant Ineligible Patients DRD or Sarclisa+Rd may still be considered in some patients Although ASCT remains the standard of care, use is likely to decline in patients who are 65-75 or with significant comorbidities Continuous therapy has resulted in better outcomes The balance of toxicity and efficacy is particularly important in this population ESPECIALLY with dexamethasone Ongoing studies will help us decide if CAR T cell therapy should move upfront and possibly even replace transplant What we do frontline has an impact in the long term...

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Breakout B RRMM: Continuing the Myeloma Treatment Journey Dr. Andrew Yee, MD

Relapsed Therapy Andrew J. Yee, MD Clinical Director, Center for Multiple Myeloma Massachusetts General Hospital Cancer Center Assistant Professor of Medicine Harvard Medical School Waltham, MA September 2025

115

OBJECTIVES



Discuss an approach to treating relapsed myeloma based on patient, disease, and treatment characteristics



Outline the key results from recent trials in relapsed disease



Discuss the approach to relapse in later lines and the use of novel therapies such as CAR T-cells and bispecific antibodies

Before 2020s: three core drug classes SLAMF7

thalidomide lenalidomide pomalidomide

cereblon

19S cap

bortezomib carfilzomib ixazomib

Immunomodulatory drugs

E3 ubiquitin ligase complex

elotuzumab

melphalan cyclophosphamide bendamustine melflufen*

20S core

CD38

Proteasome inhibitors proteasome

19S cap

venetoclax selinexor panobinostat†

HDAC

XPO1

glucocorticoid receptor

dexamethasone prednisone *Withdrawal from US market October 2021 †Withdrawn from US market November 2021

daratumumab isatuximab

Anti-CD38 monoclonal antibodies

After 2020s: BCMA therapies SLAMF7

thalidomide lenalidomide pomalidomide

cereblon

E3 ubiquitin ligase complex

elotuzumab

19S cap

bortezomib carfilzomib ixazomib

melphalan cyclophosphamide bendamustine melflufen*

20S core

proteasome 19S cap

CD38

BCMA

teclistamab Approved Oct. 2022 elranatamab Approved Aug 2023 linvoseltamab Approved July 2025

idecabtagene vicleucel March 2021 ciltacabtagene autoleucel Feb 2022

selinexor

HDAC

belantamab mafodotin‡

bispecific antibodies

venetoclax

panobinostat†

daratumumab isatuximab

CAR T-cell therapies XPO1

glucocorticoid receptor

dexamethasone prednisone

GPRC5D

talquetamab Aug 2023 bispecific antibody

*Withdrawal from US market October 2021 †Withdrawn from US market November 2021 ‡Withdrawn from US market November 2022 after accelerated approval August 2020 but may return based on recent DREAMM-7 and DREAMM-8 studies; awaiting FDA announcement October 2025

An Approach to Relapsed MM • It is not a simple algorithm of treatment #1 then #2 then #3…

• Leverage the benefit of multiple mechanisms of action in combination therapy Categories: • 1-3 prior lines • ≥4 prior lines • Triple class refractory = refractory to proteasome inhibitor (e.g. bortezomib), immunomodulatory drug (e.g. lenalidomide) and anti-CD38 monoclonal antibody (e.g. daratumumab or isatuximab)

Definitions: What is relapsed/refractory disease and a line of therapy?

• Relapsed: recurrence (reappearance of disease, progression) after a response to therapy

• Refractory: progression despite ongoing therapy • Biochemical progression: increase in M protein or free light chain values above a threshold • Clinical progression: symptoms of disease such as new bone lesions, low blood counts; new imaging findings • New line of therapy: change in treatment due to either progression of disease or unmanageable side effects • Note: initial (or induction) therapy + auto stem cell transplant + consolidation/ maintenance therapy = 1 line of therapy

Multiple myeloma is not one disease: multiple journeys Both patients have relapsed disease but treatment considerations will be different

Disease burden

Followed for MGUS Routine surveillance shows anemia, bone lesions on imaging

Initial therapy 2nd line Relapse

Maintenance

Disease burden

Presents to emergency department with fatigue and back pain and found to have bone lesions

Initial therapy

Relapse 3rd line

Relapse 2nd line

Maintenance

Relapse 4th line

Better response than initial therapy

Time

Approach to relapsed multiple myeloma Disease factors Patient factors Functional status Comorbidities Treatment history Patient preferences Eligibility and interest in a clinical trial

Biochemical (based on laboratory studies) vs clinical relapse (anemia, new bone lesions, etc.)

Earlier vs later relapse in disease course Response to previous therapy Tempo of relapse (gradual vs rapid rise in monoclonal protein, light chain) Clinical features (new bone lesions, cytopenias, renal dysfunction, extramedullary disease) Biology of disease (high-risk FISH) Actionable genetic findings: t(11;14), BRAF mutation

Choice of therapy

Treatments available now may not have been available before Overcoming drug resistance; trying therapies with new mechanisms of action

Therapy factors Route of administration Schedule Monitoring and availability of caregiver Side effect profile Availability of therapy locally v. at a major medical center Cost of therapy (e.g. oral medications)

Naked antibodies

“Naked” monoclonal antibody

Daratumumab (Darzalex) — recognizes CD38 Isatuximab (Sarclisa) — recognizes CD38 Elotuzumab (Empliciti) — recognizes SLAMF7

Multiple myeloma cell

Antibody drug conjugate (ADC) linker toxin BCMA

Example: Belantamab mafodotin (Blenrep) targets BCMA Toxin mafodotin enhances efficacy Mafodotin inhibits microtubule polymerization Induces immunogenic cell death Mafodotin associated with visual side effects (transient and reversible)

Myeloma cell

Accelerated approval August 2020 but withdrawn from US market November 2022.

May return based on recent DREAMM-7 and DREAMM-8 studies; FDA announcement expected October 2025

Bispecific antibodies

BC M A

CD3

Anti-GPRC5D Talquetamab (2023, Talvey)

D

Bispecific antibodies bind to both CD3 on T-cells and a target on myeloma cells

Anti-BCMA Teclistamab (2022, Tecvayli) Elranatamab (2023, Elrexfio) Linvoseltamab (2025, Lynozyfic)

5 RC GP

Four bispecific antibodies for two different targets on myeloma cells: BCMA and GPRC5D

CD3

T-cells T-cells Cytokine release T-cell activation Perforin, granzymes

Multiple myeloma cell death

chimeric antigen receptor

CAR T-cell

Idecabtagene vicleucel (Abecma, 2021) Ciltacabtagene autoleucel (Carvykti, 2022)

BC M A

CAR-T cells: Two approved CAR T-cells targeting BCMA

For first relapse General principles Consider mechanisms of action not previously used Triplets have more efficacy over doublets In practice, for patients receiving VRd (bortezomib, lenalidomide, dex) like regimens and who have not had an anti-CD38 monoclonal antibody, multiple options for 1st relapse: Daratumumab + pomalidomide + dex (APOLLO) Isatuximab + pomalidomide + dex (ICARIA) Daratumumab + carfilzomib + dex (CANDOR) Isatuximab + carfilzomib + dex (IKEMA) Selinexor + bortezomib + dex (BOSTON) or selinexor + carfilzomib + dex Important Update (2024) – CAR T cell therapies can be used as early as first relapse!

First or Second Relapse (Options after Considering Clinical Trials) (Modified from mSMART With New CAR T-cell Approvals) Not refractory to anti-CD38

Refractory to anti-CD38 and len

Less common with upfront use of anti-CD38

Not refractory to lenalidomide and standard risk or long 1st remission

DRd

Refractory to lenalidomide

> 2-3 year remission and standard risk

DPd or IsaPd Or DVd

< 2 year remission or HRCA

Cilta-cel CAR T or anti-CD38 + Kd

Standard risk and >2-3 years remission

<2 years of remission and/or HRCA

KPd, KCd, PVd PCd, EloPd Or CAR T (Cilta-cel if 1+ prior LOT, Ide-cel if 2+ LOT)

CAR-T Cilta-cel (1+ prior LOT) Or Ide-cel (2+ prior LOT) Others to the left if not candidate for CAR-T

HRCA = high risk chromosomal abnormalities e.g. del17p, t(4;14), t(14;16) Dingli D, et al. Mayo Clin Proc. 2017;92(4):578-59.

t(11;14) present

venetoclax-based combinations

C = cyclophosphamide D = daratumumab d = dexamethasone Elo = elotuzumumab Isa = isatuximab K = carfilzomib (Kyprolis) P = pomalidomide R = lenalidomide (Revlimid) V = bortezomib (Velcade)

CAR T-cell therapy: from experimental to now standard of care

December 2012

UPenn (class of 2027)

CAR T-cell therapy: from experimental to now standard of care Axicabtagene ciloleucel approved in October 2017 for diffuse large B-cell lymphoma

December 2012

UPenn (class of 2027)

June 5, 2025

Tisagenlecleucel approved in August 2017 for acute lymphoblastic leukemia

Ciltacabtagene autoleucel (Carvykti) approved in 2022 for multiple myeloma

Ide-cel CAR T (Abecma) vs standard of care: 2-4 prior lines of therapy, triple class exposed

SOC = DPd, Kd, elo Pd, ixa Rd, DVd Rodriguez-Otero P et al., N Engl J Med 2023

Cilta-cel CAR T (Carvykti) vs standard of care: 1-3 prior lines of therapy, lenalidomide refractory

SOC = DPd, PVd Mateos M-V et al., IMS 2024

OVERALL RESPONSE RATE AND PFS OF RECENTLY APPROVED THERAPIES IN RRMM ≥4 LOT* and triple refractory ORR, %

120

ORR, %

100

PFS, months 81

80

70

63

fil zo m ib -d ex

33

24

20

4 0

Ca r

PFS, months;

60 40

100

98

Pom Dex

4

Car-Dex

Richardson Blood 2014; 123:1826-32 Siegel Blood 2012; 120:2817-25 Lonial Lancet 2016; 387:1551-60 Rasche EHA 2024, P915

61

35

29

26 4

Dara

4

11.2

11

17

Selinexor Talquetamab Teclistamab Elrantamab

*Ide-cel approved after 2 prior lines *Cilta-cel approved after 1 prior line

12 Ide-Cel

11.4 Cilta-Cel

OriCAR-017

Van de Donk ASCO 2023; abs 8011 Lesokhin Nat Med 2023; 29:2259-67 Munshi NEJM 2021; 384:705-16 Munshi EHA 2023; S202 Huang ASCO 2024; 7511 ©2025 Mayo Foundation for Medical Education and Research | WF888874-133

CAR T-cell therapy in multiple myeloma available in earlier lines of therapy Idecabtagene vicleucel (Abecma) Approved in 4 prior lines, triple class exposed (March 2021)

2021

Ciltacabtagene autoleucel (Carvykti)

CAR T is more accessible as more sites become active No more waiting lists

2022

Approved in 4 prior lines, triple class exposed (February 2022)

2023

Approved in 2 prior lines, triple class exposed (April 2024)

What’s new in 2025

2024

Approved in 1 prior line, lenalidomiderefractory (April 2024)

Ongoing trials in newly diagnosed multiple myeloma

More patients will be eligible for CAR T-cell therapy as indications move to earlier lines of therapy

CAR T-Cell Therapy Patient Journey Apheresis

(Manufacturing) Patients return home

1

2

1 day

Immune cells from the patient are collected

4–6 weeks

Standard of care therapy (bridging) until CAR T-cells are ready for infusion Fludarabine and cyclophosphamide are used to create “immunologic space” to CAR T cells to expand

Lymphodepletion (chemotherapy)

3

3 days

Infusion

4

2 weeks

Follow up 5

Within 2 weeks

Infusion of CAR T-cells may occur in the hospital or may occur as an outpatient Monitoring for side effects may occur in the hospital (~1 week) and as an outpatient in proximity of the hospital

CAR T: Expected side effects in first 2 weeks

Immune effector cell-associated neurotoxicity syndrome

CRS

Cytokine release syndrome (CRS)

Cytopenias

Onset

19 days after CAR T-cell infusion

29 days after CAR T-cell infusion

Duration

511 days

317 days

Symptoms

• Fever • Difficulty breathing • Dizziness • Nausea • Headache • Rapid heartbeat • Low blood pressure

• Headache • Confusion • Language disturbance • Seizures • Delirium • Cerebral edema

Management

• Tocilizumab • Corticosteroids • Supportive care

• Corticosteroids • Anti-seizure medications

Neurotoxicity (ICANS)

Infections

ICANS

CRS: fever is common; uncommon low blood pressure, need for ICU is ICANS: some patients may have transient confusion After two weeks, CRS and ICANS have generally resolved Monitoring for above generally involves hospitalization (about 1 week)

Xiao X et al. J Exp Clin Cancer Res. 2021;40(1):367. Lee DW et al. Biol Blood Marrow Transplant. 2019;25:625; Shah N et al. J Immunother Cancer. 2020;8:e000734.

CAR T-cell therapy: other side effects in first month • Blood counts can take take time to recover • With cilta-cel: small risk of parkinsonism (~5% in initial trials, ~0.5% in more current trials) • Most cases are reversible with supportive care, chemotherapy

• With cilta-cel: Bell’s palsy ~7% , transient • Small risk of second blood cancer like leukemia While neurological side effects above (mainly with cilta-cel) can occur, strategies at managing these are improving.

Beyond a month, patients are feeling well off therapy.

Bispecific antibodies: practical considerations

• Cytokine release syndrome (CRS) (less than CAR T-cells) • First 2-3 doses involve step up dosing to minimize risk of CRS • Monitoring for CRS during step up dosing • Hospitalization per label, but increasingly this is being done as outpatient • More and more sites have the capability to administer bispecific antibodies

• Minimize risk of infections with IVIG (with anti-BCMA) • Dosing can be spaced out since deep responses happen early • Some side effects are target dependent. With GPRC5D,

Anti-BCMA therapies Approved product

Efficacy

Anti-BCMA bispecific antibody

Anti-BCMA CAR T-cell

Teclistamab Elranatamab Linvoseltamab

Idecabtagene vicleucel Ciltacabtagene autoleucel

+++ Combinations under investigation

++++

How given

Weekly to biweekly to monthly until progression

“One-and-done” Trials evaluating addition of maintenance therapy and consolidation

Notable adverse events

Infection, hypogammaglobulinemia

CRS and neurotoxicity Late neurotoxicity with movement disorders (cilta-cel) Immune effector cell diarrhea (cilta-cel)

Cytokine release syndrome

++

+++

Neurotoxicity

Rare

+

Availability

Off-the-shelf; hospitalization for initial step-up dosing (but outpatient initiation increasing)

Limited to major medical centers Wait time for manufacturing; hospitalization for monitoring

Ongoing randomized studies evaluating above therapies in earlier lines of treatment, including in newly diagnosed patients

Emerging Therapies for Relapsed/Refractory Multiple Myeloma Bispecific antibodies and trispecific antibodies

CAR T-cell therapies in development

• Etentamig, another anti-BCMA bispecific antibody with a favorable dosing schedule • Cevostamab targeting a new cell surface protein, FcRH5 • Combinations of bispecific antibodies with e.g. daratumumab, being evaluated in earlier lines of therapy, including newly-diagnosed patients • Trispecific antibodies: an antibody that can bind to three proteins all at once (e.g. BCMA,GPRC5D, and CD3 on T-cells)

• Anito-cel (Arcellx), an anti-BCMA CAR T-cell in clinical trials, may be approved in 2026, favorable profile • GC012F (AstraZeneca), targets both BCMA and CD19 • Anti-GPRC5D CAR T-cells

Cereblon E3 ligase modulators (CELMoDs) • Iberdomide, mezigdomide, cemsidomide • More potent inhibition of cereblon (compared to lenalidomide and pomalidomide) • Enhances tumoricidal and immune-stimulatory effects compared with immunomodulatory agents

Small molecule inhibitors • Sonrotoclax (similar to venetoclax), in t(11;14); targets Bcl-2 • p300/CBP inhibitors (inobrodib, OPN-6602)

With recently approved therapies and therapies on the horizon, patients are living longer and better, and we are getting closer to a cure.

1

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LUNCH

Please remain in this room

Walk Through the IMF Website Robin Tuohy Vice President, Support Groups, International Myeloma Foundation

IMF REGIONAL COMMUNITY WORKSHOP WALTHAM AFTERNOON AGENDA

Seasons of Myeloma: Managing Side Effects and Living Well Kimberly Noonan, DNP, ANP-BC, AOCN, FAAN VNA Care Living the Myeloma Life: Local Patient & Care Partner Jill Zitzewitz (Patient) and Osman Bilsel (Care Partner) Beyond Myeloma Therapy: Unlocking Emotional Freedom Technique (EFT) and Stress Management Rebecca Rooney, PhD Retired Lt. Col. U.S. Army, Clinical Psychologist Q&A with Panel Closing Remarks Robin Tuohy Vice President, Support Groups, International Myeloma Foundation

144

Walk Through the IMF Website Robin Tuohy, Vice President, Support Groups International Myeloma Foundation

Seasons of Myeloma: Managing Side Effects and Living Well Kimberly Noonan, DNP, ANP-BC, AOCN, FAAN VNA Care

Seasons of Multiple Myeloma

Kimberly Noonan, DNP, ANP-BC, AOCN, FAAN IMF Nurse Leadership Board member VNA Care

Wintery Mix of Treatment Options

Spring into Managing Side Effects

Summer of Success

Enjoy Life’s Bounty

Wintery Mix of Treatment Options

150

V

Diverse and Complex Treatment Combinations Myeloma Treatment

WINTERY MIX OF TREATMENT OPTIONS

Common Combinations

Velcade® (bortezomib) DVRd, VRd, Vd Lenalidomide DVRd, VRd, Rd Kyprolis® (carfilzomib) KRd, Kd, DKd, Isa-Kd Pomalyst® (pomalidomide) Pd, DPd, EPd, PCd, Isa-Pd Darzalex® (daratumumab) DVRd, DRd, DVd, DPd, DVMP, DKd Ninlaro®(ixazomib) IRd Empliciti® (elotuzumab) ERd, EPd Xpovio® (Selinexor) XVd, XPd, XKd Sarclisa® (Isatuximab) Isa-Kd, Isa-Pd Blenrep® (Belantamab mafodotin) Bela-d Abecma® (Idecabtagene Vicleucel) -Carvykti® (ciltacabtagene autoleucel) -Elrexfio® (elranatamab) -Lynozyfic™ (linvoseltamab) Tecvayli® (teclistamab) -Talvey® (talquetamab) -Venclexta® (venetoclax) Vd + ven New agents or regimens in clinical trials are possible options ASCT = autologous stem cell transplant; Bela = belantamab; C = cyclophosphamide; D = daratumumab; d = dexamethasone; E = elotuzumab; Isa = isatuximab; I = ixazomib; K = carfilzomib; M = melphalan; P = pomalidomide; R = lenalidomide; V = bortezomib; ven = venetoclax.

Prescribing information. NCCN Guidelines. Multiple Myeloma. V2.2024. Accessed February 5, 2024.

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WINTERY MIX OF TREATMENT OPTIONS

Stem Cell Transplant

Duration: Approximately 2 weeks Location: Transplant Center

High Dose Chemotherapy Stem Cell Infusion Supportive Care Engraftment

Duration: Approximately 3-4 weeks Location: Transplant Center

POST-TRANSPLANT

PHASE 3

Measuring Treatment Response Determining Transplant Eligibility Insurance Authorization Collecting Stem Cells

TRANSPLANT

PHASE 2

PHASE 1

ELIGIBILITY

Restrengthening Appetite recovery “Day 100” assessment Begin maintenance therapy

Duration: Approximately 10-12 weeks Location: HOME

Upfront stem cell transplant remains the standard of care for eligible patients Miceli T, et al. Clin J Oncol Nurs. 2013;17(6)suppl:13-24. Miceli and Steinbach, 2021. Stem Cell Transplant, Ch4, ONS. NCCN Guidelines. Multiple Myeloma. V1.2025. Accessed February 6, 2025. To view the most recent or complete version of the guideline, go online to NCCN.org.

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WINTERY MIX OF TREATMENT 152 OPTIONS

CAR T: Another Treatment Approach

No driving for 8 weeks “One & Done” with continued monitoring

Ask for a referral to CAR Tcell center as soon as it is possible as next treatment option (ie, before relapse)

Manufacturing takes ≈ 4 to 6 weeks

• • • • •

Bridging therapy may be needed T-Cell Collection

• • •

CAR = chimeric antigen receptor; CRS = cytokine release syndrome; ICANS = Immune Effector Cell-Associated Neurotoxicity Syndrome

Away from home Often some hospital stay Care Partner needed

Side effect management CRS, ICANS Low blood counts Fatigue and fever Some patients need ongoing transfusion support

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WINTERY MIX OF TREATMENT OPTIONS

Bispecific Antibodies • Different bispecific antibodies have differences in efficacy, side effects – Available after 4 prior lines of therapy (or clinical trial) – About 7 in 10 patients respond – Off-the-shelf treatment; no waiting for engineering cells – CRS and neurotoxicity – Risk of infection • BCMA target: greater potential for infection – Tecvayli® (teclistamab) – Elrexfio ® (elranatamab) – Lynozyfic™ (linvoseltamab) • GPRC5D target: potential for skin and nail side effects, GI issues of taste change, anorexia and weight loss – Talvey ® (talquetamab)

BISPECIFIC ANTIBODIES Cytotoxic cytokines MM cell

T cell

CD3

Target

Bispecific antibody

MM cell death

BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; GPRC5D = G protein–coupled receptor, class C, group 5, member D; MM = multiple myeloma; scFV = single chain fragment variable. Shah N, et al. Leukemia. 2020;34(4):985-1005. Yu B, et al. J Hematol Oncol. 2020;13:125.

154

CAR T and Bispecific Antibodies: Unique Side Effects

WINTERY MIX OF TREATMENT OPTIONS

Fever Confusion

Weakness

Fatigue

Cytokine Release Syndrome

Diarrhea Shortness of Breath

Headache

CRS is a common but often mild & manageable side effect

Nausea / vomiting

CAR = chimeric antigen receptor; CRS = cytokine release syndrome.

Oluwole OO, Davila ML. J Leukoc Biol. 2016;100:1265-1272. June CH, et al. Science. 2018;359:1361-1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45-55. Shimabukuro-Vornhagen, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.

155

CAR T and Bispecific Antibodies: Unique Side Effects

WINTERY MIX OF TREATMENT OPTIONS

Headache Confusion

Encephalopathy

Neurotoxicity is a rare but serious side effect

Altered wakefulness

Seizures

NEUROTOXICITY Tremors

Facial nerve palsy

CAR = chimeric antigen receptor.

Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.

Hallucinations

Ataxia Apraxia

Spring Into Managing Side Effects

157

The Early Bird Gets the Worm: Communicate Proactively with Your Healthcare Team

SPRING INTO SIDE EFFECT MANAGEMENT

Your team may be able to help, but only if they know how you feel.

Unmanaged Myeloma can cause: • • • • • • • •

Calcium elevation Renal dysfunction Low blood counts Infection Risk Blood clots Bone pain Neuropathy Fatigue

How You Feel

Side Effects of Treatment can cause: • • • • • • •

GI symptoms Renal dysfunction Low blood counts Infection Risk Blood clots Neuropathy Fatigue

Tip: Keep a Symptom Diary and bring it to appointments

Tip: proactively discuss common side effects and what to do if they occur

158

Are Steroids Messing With Your Sunny Disposition?

Steroids enhance the effectiveness of other myeloma therapies Your provider may adjust your dose. Do not stop or alter your dose of steroids without discussing it with your provider

Steroid Side Effects • Irritability, mood swings,

• Difficulty sleeping

• Blurred vision, cataracts

• Flushing/sweating

• Increased risk of infections,

• Stomach bloating, hiccups,

• Muscle weakness,

• Weight gain, hair

• Increased blood pressure,

• Increased blood sugar

depression

Managing Steroid Side Effects

• Consistent schedule (AM vs. PM) • Take with food • Stomach discomfort: Over-the-counter or

prescription medications • Medications to prevent shingles, thrush, or other infections

heart disease cramping

water retention

Rajkumar SV, et al. Lancet Oncol 11(1):29–37. King T, Faiman B. Clin J Oncol Nurs. 2017;21(2):240-249.

SPRING INTO SIDE EFFECT MANAGEMENT

(insomnia), fatigue

heartburn, ulcers, or gas

thinning/loss, skin rashes levels, diabetes

159

Infection Can Be Serious for People With Myeloma

SPRING INTO SIDE EFFECT MANAGEMENT

Preventing infections is paramount.

Infection remains the leading cause of death in patients with multiple myeloma. Several factors account for this infection risk, including the overall state of immunosuppression from multiple myeloma, treatment, age, and comorbidities (e.g., renal failure and frailty).

Report fever of more than 100.4°F, shaking chills even without fever, dizziness, shortness of breath, low blood pressure to HCP as directed.

IMWG Consensus guidelines and recommendations for infection prevention in multiple myeloma; Lancet Haematol.2022;9(2):143–161.

Infection Prevention Tips Good personal hygiene (skin, oral)

As recommended by your healthcare team: Environmental control

(avoid crowds and sick people; use a high-quality mask when close contact is unavoidable)

IMWG = International Myeloma Working Group; HCP = healthcare provider.

Raje NS, et al. Lancet Haematol.2022;9(2):143–161. IMF Nurse Leadership Board ONS Symposia 2023.

Immunizations:

Flu, COVID, RSV & and pneumococcal vaccinations; avoid live vaccines

Preventative and/or supportive medications (next slide)

160

Medications Can Reduce Infection Risk

SPRING INTO SIDE EFFECT MANAGEMENT

Type of Infection Risk

Medication Recommendation(s) for Healthcare Team Consideration

Viral: Herpes Simplex (HSV/VZV); CMV

Acyclovir prophylaxis

Bacterial: blood, pneumonia, and urinary tract infection

Consider prophylaxis with levofloxacin

PJP (P. jirovecii pneumonia)

Consider prophylaxis with trimethoprim-sulfamethoxazole

Fungal infections

Consider prophylaxis with fluconazole

COVID-19 and Influenza

Antiviral therapy if exposed or positive for covid per institution recommendations

IgG < 400 mg/dL (general infection risk)

IVIg recommended

ANC < 1000 cells/μL (general infection risk)

Consider GCSF 2 or 3 times/wk (or as frequently as needed) to maintain ANC > 1000 cells/μL and maintain treatment dose intensity

Some people receiving BCMA-targeting therapies have experienced infections that are less common like CMV, PJP and fungal infections ANC = absolute neutrophil count; BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; CMV, cytomegalovirus; GCSF = granulocyte colonystimulating factor; HSV = herpes simplex virus; IVIg = intravenous immunoglobulin; PJP = Pneumocystis jirovecii pneumonia; VZV = varicella zoster virus.

Raje NS, et al. Lancet Haematol.2022;9(2):143–161.

161

GI Symptoms: Prevention & Management

SPRING INTO SIDE EFFECT MANAGEMENT

Fluid intake can help with both diarrhea and constipation and helps kidney function

Constipation is more common in the induction phase • Opioid pain relievers, antidepressants, heart or blood pressure medications (check with provider, pharmacist) • Supplements: Calcium, Iron, vitamin D (rarely), vitamin B-12 deficiency Increase fiber • Stay well hydrated • Fruits, vegetables, high fiber whole grain foods • Fiber binding agents – Metamucil®, Citrucel®, Benefiber®

Anorexia, the inability to eat, is

common during transplant and resolves with time.

• Hydration is most important • Small, frequent meals with a focus on protein intake • You will work closely with a dietician to help monitor your calorie intake

Smith LC, et al. Clin J Oncol Nurs. 2008;12(3)suppl:37-52. Faiman B. Clin J Oncol Nurs. 2016;20(4):E100-E105.

Diarrhea is common during transplant

and long-term maintenance therapy.

Other medications and supplements • Hydration is very important • Electrolyte replacement is common • Good skin care will help prevent irritation • Stool exam may be needed to rule-out infection • If no infection, anti-diarrheal medication may be prescribed

Discuss GI issues with healthcare providers to identify causes and make adjustments to medications and supplements

162

SPRING INTO SIDE EFFECT MANAGEMENT

Management of Oral Side Effects

Dry Mouth

OTC dry mouth rinse, gel, spray are recommended. Advise patients to avoid hot beverages. Initiate anti-fungal therapy for oral thrush

Taste Changes

Dexamethasone oral solutions “swish and spit” have been tried but with no proven benefit yet. Sour citrus or candies before meals are also recommended.

Dental Care

Catamero D, Purcell K, Ray C, et al. Presented at the 20th International Myeloma Society (IMS) Annual Meeting Nurse Symposium; September 27–30, 2023; Athens, Greece.

Attention to oral hygiene.

Regular dental cleaning and evaluation. Close monitoring for ONJ, oral cancer and dental caries

OTC = Over The Counter ONJ = Osteonecrosis of the Jaw

Dysphagia

Weight Management

Dietary modifications with small bites, eating upright, and sips with food can help manage symptoms.

Some medications lead to weight gain, others to weight loss.

Dry mouth leads to taste changes which can lead to anorexia.

Meet with a Nutritionist Consider diet changes, supplements Monitor weight

Education and emotional support are key strategies to manage oral toxicities.

163

SPRING INTO SIDE EFFECT MANAGEMENT

Skin and Nail Side Effects Possible side effect to some treatments and supportive care medications Skin Rash: • Prevent dry skin; apply lotion • Report changes to your care team • Medication interruption or alternative, as needed • Steroids: – Topical for grades 1-2, – Systemic and topical for Grade 3 • Antihistamines, as needed

Nail Changes: • Keep your nails short and clean.

Photos: Mount Sinai Hospital, NY, NY Nurse Leadership Board

Watch for “catching and tearing” • Apply a heavy moisturizer like Vaseline or salve. Wear cotton hand coverings to bed • A nail hardener may help with thinning • Tell the team if you have signs of a fungal infection, like thickened or discolored nails

164

Feel Like a Spring Chicken: Prevent and Manage Pain

SPRING INTO SIDE EFFECT MANAGEMENT

Pain can significantly compromise quality of life

Sources of pain include bone disease, neuropathy and medical procedures

• Management – Prevent pain when possible • Bone strengtheners to decrease fracture risk • Antiviral to prevent shingles • Sedation before procedures

– Interventions depend on source of pain • May include medications, activity, surgical intervention, radiation therapy, etc • Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture, etc) • Scrambler therapy for neuropathy

Faiman B, et al. CJON. 2017;21(5)suppl:19-36.

Tell your healthcare provider about any new bone or chronic pain that is not adequately controlled

165

SPRING INTO SIDE EFFECT MANAGEMENT

Peripheral Neuropathy Management

Peripheral neuropathy happens when there is damage to nerves in the extremities (hands, feet, limbs). Damage can be the result of myeloma, treatment or unrelated conditions (i.e. diabetes).

Symptoms:

• Numbness • Tingling • Prickling sensations • Sensitivity to touch • Burning and/or cold

Prevention / management:

• Bortezomib once-weekly and/or

If neuropathy worsens, your provider may:

• Adjust your treatment plan subcutaneous administration • Prescribe oral or topical • Massage area with cocoa butter pain medication regularly • Suggest physical therapy • Neuroprotective Supplements: – B-complex vitamins (B1, B6, B12) sensation – Green tea • Muscle weakness • Safe environment: rugs, furnishings, Report symptoms ofshoes peripheral neuropathy early to your healthcare provider;

nerve damage from neuropathy can be permanent if unaddressed

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Tariman, et al. CJON.2008;12(3)suppl:29-36. Zhao T, et al. Molecules. 2022;27(12):3909.

166

Understanding Changes to Kidney Function

SPRING INTO SIDE EFFECT MANAGEMENT

• Risk Factors – Active multiple myeloma (light chains, high calcium) – Other medical issues (ex: Diabetes, dehydration, infection) – Medications (MM treatment, antibiotics, contrast dye) – Poor Nutrition • Prevention – Stay hydrated – drink water – Avoid certain medications when possible (eg, NSAIDs), dose adjust as needed • Treatment – Treatment for myeloma Many myeloma patients will experience kidney issues at – Hydration some point; protecting your kidney function early and – Dialysis

over time is important

Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76.

167

SPRING INTO SIDE EFFECT MANAGEMENT

Additional Supportive Care DVT/PE Prevention

Bone Health

Fatigue

Anxiety

Blood thinners Ex: Aspirin, DOACs

Bone Strengthening Agents Calcium Vitamin D

Stimulant medications Red Cell Transfusion (anemia)

Anti-depressants Anti-anxiety

Non-medication Therapies

Compression stockings

Radiation Surgery Immobilization Physical therapy

Relaxation Meditation

Therapy Relaxation Meditation

Lifestyle Options

Activity Stop smoking Weight loss

Activity

Activity Improved sleep

Activity Improved sleep

Supportive Medications

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36.

Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.

Summer of Success

169

SUMMER OF SUCCESS

Let the Sun Shine In Fatigue

98.8%

Fatigue is the most reported symptom.

Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression

Often, people do not share these symptoms with their providers.

Talk to your provider about symptoms that are not well controlled or if you have thoughts of self-harm.

Anxiety

Depression

>35%

≈25%

of patients

of patients

Help is available.

170

SUMMER OF SUCCESS

Bee an Empowered Patient Ask questions – – – – – – –

What are my treatment options?

What are the pros and cons of the different options?

How will we know if treatment is working?

What do the different labs mean?

Who will be monitoring my labs?

Live in the How can I access my test results sunshine, swim (eg, patient portal)? the sea, drink What will we do if my treatment the wild air. doesn’t work or quits working?

Participate in decisions – Share your priorities and preferences – Include care partner(s) in your discussion

– Ralph Waldo Emerson

Speak up if something seems different or unusual – – –

Normally 4 vials of blood but only drawing 3?

Normally specialty pharmacy confirms delivery but haven’t heard from them this month?

When is my next appointment?

Communicate with your healthcare team – Understand the roles of each team member – Who to contact for your needs (eg, side effects, insurance issues, other)

Develop a support network – Learn from others: IMF has many support groups or you can start one (IMF’s can help)

170

171

SUMMER OF SUCCESS

Care Partners Are Vital for Success If you want to go fast, go alone, if you want to go far, go together African Proverb

• Care partners may help with medical appointments,

managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions • Care partners can be a spouse, close relative, a network of people (family, friends, neighbors, church members, etc)

IMF Care Giver Tip Card

• Caring for the Care Partner – Recognize that caregiving is difficult/stressful – Encourage care partners to maintain their

health, interests, and friendships – The IMF has information and resources to help care partners

172

SUMMER OF SUCCESS

Cultivate A Care Network If you want to go fast, go alone, if you want to go far, go together African Proverb

• Multiple studies demonstrate that strong

social ties are associated with longevity, improved adherence to medical treatment and overall improved health outcomes • Care partners can be a spouse, close relative, a network of people (family, friends, neighbors, church members, etc) • Care partners may help with medical appointments, managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions

• Caring for the Care Partner – Recognize that caregiving is

difficult/stressful – Encourage care partners to maintain their health, interests, and friendships – The IMF has information and resources to help care partners IMF Care Giver Tip Cards

Martino J, et al. Am J of Lifestyle Med. 2015;11(6):466-475. Yang YC, et al. Proc Natl Acad Sci U S A. 2016;113(3):578-583. Pinquart M and Duberstein PR. Crit Rev Oncol Hematol. 2010; 75(2):122–137.

Enjoy Life’s Bounty

174

ENJOY LIFE’S BOUNTY

Harvest Good Health Have a Primary Care Provider & Have Recommended Health Screenings • Blood pressure • Cholesterol • Cardiovascular disease • Diabetes • Colonoscopy • Women specific: mammography, pap smear • Men specific: prostate • Vision • Hearing • Dermatologic evaluation • Dental checkups & cleaning

Develop & maintain healthy behaviors • Good nutrition • Regular activity • Quit tobacco use • Sufficient Sleep (next slide)

An ounce of prevention is worth a pound of cure.

Benjamin Franklin

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56.

Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.

175

IMF Offers an Abundance of Resources

Download or order at myeloma.org

ENJOY LIFE’S BOUNTY

Website: http://myeloma.org

Videos

IMF InfoLine 1-800-452-CURE & Myelo

eNewsletter: Myeloma Minute

You are not alone!

Living the Myeloma Life: Local Patient & Care Partner Jill Zitzewitz (Patient Advocate) & Osman Bilsel (Care Partner)

LIVING THE MYELOMA LIFE: LESSONS LEARNED September 27, 2025 Jill Zitzewitz (patient) & Osman Bilsel (care partner)

 Share a Bit of Our Story  Share Lessons We Learned Along Our

AGENDA

Myeloma Journey

 Hear Your Stories & Lessons Learned  Goal: Build Community & Learn From

Each Other

178

A LITTLE BIT ABOUT US AND LESSONS WE LEARNED ALONG THE WAY

Lesson 1: Your Life Journey Matters & Prepares You For What’s We just celebrated 29 years of marriage, and we’re the Ahead parents of 4 beautiful young adult children.

•

•

We are scientists & have worked together for most of our career.

•

We are very involved in our faith, town, and work communities.

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

180

Lesson 2: You’re Not Alone – Seek Out Support

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

181

Lesson 2b: Join a Myeloma Support Group •

Other myeloma patients and care partners understand in ways that your extended family, friends, and community members just don’t because they haven’t experienced what you are experiencing.

•

Myeloma support groups provide communities of support, educational information, inspiration, and often lead to new friendships.

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

182

Lesson 3: Knowledge is Power – Use Reliable

Be your own best advocate, ask your myeloma specialist Sources questions, and seek out reliable sources of information about your myeloma.

•

•

International Myeloma Foundation website is amazing!  Support group finder, nurse’s hotline, clinical trial finder, Gen AI tool Myelo!

• Don’t consult Dr. Google! – Instead, ask Myelo!

•

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

183

Lesson 4: Take Care of Yourself •

Make time for things that bring you joy and fill you up!

•

Ensure that care partners also have time for themselves.

•

Don’t be afraid to ask for help or to help others when you can.

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

184

Lesson 5: Never Lose Hope!

•

There are people who care about you and want to help you on your journey.

•

Education and research is leading to earlier diagnosis and better outcomes with less suffering for patients and their families.

•

Basic science has led to many new therapeutic options for myeloma patients so they can live longerand better lives.

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

185

WHAT LESSONS HAVE YOU LEARNED?

© 2025, International Myeloma Foundation. All rights reserved. IMF Confidential

Beyond Myeloma Therapy: Unlocking Emotional Freedom Technique (EFT) and Stress Management Rebecca Rooney, PhD Retired Lt. Col. U.S. Army, Clinical Psychologist

Emotional Freedom Techniques: EFT Presentation for IMF Regional Community Workshop Rebecca Rooney, PhD, Lieutenant Colonel, US Army (Retired)

Goals for the Day  Learn EFT  Understand the theory and history of  Understand when and why to use EFT  Understand the versatility of EFT  Grow and have fun  YOUR GOALS?

EFT

First Assignment  Write down some issues that cause you stress or distress  Rate the level of distress from 0 (no distress) to 10 (the WORST you could

feel)  Pick one issue that you want to resolve today  Highlight that issue  Tap on that issue at some point today

Background

What is EFT?  Energy Psychology : “acupressure for the emotions”  Energy Meridians, Acupuncture, Acupressure  Emotional and Physical Challenges  Blocked Energy  Tapping  Change  Healing

THIS IS EFT.

EFT Tapping Points

The Basic EFT Protocol

1. Choose a problem or issue (this craving for chocolate; this

anxiety, etc) 2. Rate the level of disturbance (SUD) from zero (0) to ten (10).

3. Set up Phrase: “Even though I have this-------------, I deeply and completely accept myself.” (3 times) 4. TAP about 5-7 times on each point, saying “this ------”.

5. Breathe. Notice thoughts and feelings. Check SUD. If not zero, 6. Repeat #3 and #4 saying: “Even though I still have this ---” and “this remaining ---------”.

EFT

LET’S JUST DO IT!

Energy Psychology  EINSTEIN: e = mc2 Matter = Energy  Therapies that work directly on and in the body to produce psychological

change  Visualization and Verbalization  SPECIFIC Routines: tapping, touching, breathing, massage

Energy Psychology  Recall + Physical Stimulation = Relief  Focus + Physical Stimulation = Change  Methods:  Thought Field Therapy TFT : Roger Callahan, PhD  Meridian Tapping Techniques  Tapas Acupressure Techniques  Emotional Freedom Techniques: Gary Craig

When to use EFT  Stressors  Anxiety, fear, disappointment, uncertainty, anger  Pain: Headaches, backaches, bunions   Finances  Self-sabotage  Weight Loss  Self Care  Identity Issues  Saying NO  Fear of Change  Relationships  Sports Performance  Whenever !

The Choices Method  Patricia Carrington, PhD  “Accept myself” ????  Use CHOICE phrase instead  “Even though I have this ------, I CHOOSE to have --------.”  CHOICES TRIO:  Negative Phrase  Positive Phrase  Alternate Phrases

CHOICES DEFAULT PHRASES  I choose to be calm and confident.  I choose to feel comfortable and at ease.  I choose to be in harmony with (name the person with whom you are

experiencing some difficulty).  I choose to enjoy myself and be happy.  I choose to be loving, kind and compassionate.  I choose --------

EFT

JUST DO IT!

Other Energy and EFT Options and Methods Something for Everyone.

JUST Do It.

Touch and Breathe  Touch each point gently with fingertip(s)  Take an easy, deep breath at each point and let the breath out slowly  Repeat your tapping phrase still touching the spot with your fingertip(s)  Use to go to sleep, in public places, or to create a quiet, meditative mood

The SORE Spot  Two locations, one on each side of the chest  Painful to press on  Use in a crisis or when full tapping is not possible  Rub or palpitate the spot  Breathe  Release  CALM will come (most of the time)

Discreet Tapping  Fingertip Tapping  Use thumb to tap on ends of fingers  Touch, rub or hold any of the energy points  Simple Energy Techniques (SET)

Simple Energy Techniques (SET)  Tap lightly on the Energy Points while focusing on a problem  Focus on bodily feelings, anxiety, or thoughts  Regularly check emotional intensity  Continue and be aware of other issues, aspects, thoughts, events,

memories  PERSIST and recognize many possible ASPECTS  Tap daily for ENERGY TONING

EFT with Power Memories  Positive Personal Resources  Effective Coping Experience  Personal Memory  Borrowed Memory  Collect Power Memories DAILY  Regularly TAP on Power Memories  Use them when you really need to ……and when you think you don’t!

REMEMBER: When you can’t do EFT in public, or if you don’t want to, you can almost always go to the restroom and tap.

EFT

JUST DO IT!

Tapping with Children  Tap on YOURSELF first  Match the tapping to the child  Match the child’s language  Tap at the child’s pace  Use books and pictures to help

 Introduce tapping as a game: Dance with your fingers  On special points on your body  Help you feel good 

Children’s Book  “The Wizard’s Wish: Or, How He Made the Yuckies Go Away

– A Story about the Magic in You” by Brad Yates

 A bad storm disrupts a village. The Village Wizard discovers a way to

make himself and the people in his village feel better. They simply need to use their finger tips to tap on some magic points to get rid of the yuckies. They end up feeling even happier.

Tell the Story Technique Bodily Sensation Based  Think of an experience that disturbs you  Rate the disturbance; locate it in your body  Tell the Story as you remember it  Check often for clearing or blocks  Tap through the feelings when apparent

Borrowing Benefits  Go back to the issue you started with this morning  Rate the level of intensity of the disturbance now  Review some of the other issues you wrote about  Just tapping with another person or other people can help reduce and heal

our own issues because we are still changing the energy in the body.

Personal Peace Procedure  Write down every specific troublesome event  Give each event a specific Title  Rate the events starting with the worst  Tap on one event at a time to a SUD of zero  Clear one to three events DAILY  Pay attention to your body, your emotions and your relationships for over

time  Check for the EFT Generalization Effect

EFT Humanitarian Projects  The Tapping Solution for Newtown: Stress and

Project - Nick Ortner  Iraq Veterans Stress Project - Gary Craig, Dawson Church, Gary Feinstein  World Trade Center  Rwandan Genocide project

Trauma Relief Marilyn McWilliams,

EFT: Making a Difference “We must not, in trying to think about how we can make a big difference, ignore the small daily differences we can make which, over time, add up to big differences that we often cannot foresee.”

Marion Wright Edelman

EFT Research Veterans: Five Studies Rwandan Genocide Survivors (single session) Refugees and Immigrants to the US Peruvian Male Adolescents (single session)

EFT Research Journal of Nervous & Mental Disease:  February 2013 - Volume 201 - Issue 2 - p 153–160  doi: 10.1097/NMD.0b013e31827f6351  Original Articles

Psychological Trauma Symptom Improvement in Veterans Using Emotional Freedom Techniques: A Randomized

Controlled Trial

 Church, Dawson PhD*; Hawk, Crystal MEd†; Brooks, Audrey J. PhD ‡; Toukolehto, Olli MD §; Wren, Maria LCSW∥; Dinter,, Ingrid¶; Stein, Phyllis PhD #  Abstract

Abstract: This study examined the effect of Emotional Freedom Techniques (EFT), a brief exposure therapy combining

cognitive and somatic elements, on posttraumatic stress disorder (PTSD) and psychological distress symptoms in veterans receiving mental health services. Veterans meeting the clinical criteria for PTSD were randomized to EFT (n = 30) or standard of care wait list (SOC/WL; n = 29). The EFT intervention consisted of 6-hour–long EFT coaching sessions concurrent with standard care. The SOC/WL and EFT groups were compared before and after the intervention (at 1 month for the SOC/WL group and after six sessions for the EFT group). The EFT subjects had significantly reduced psychological distress (p < 0.0012) and PTSD symptom levels (p < 0.0001) after the test. In addition, 90% of the EFT group no longer met PTSD clinical criteria, compared with 4% in the SOC/WL group. After the wait period, the SOC/WL subjects received EFT. In a within-subjects longitudinal analysis, 60% no longer met the PTSD clinical criteria after three sessions. This increased to 86% after six sessions for the 49 subjects who ultimately received EFT and remained at 86% at 3 months and at 80% at 6 months. The results are consistent with that of other published reports showing EFT’s efficacy in treating PTSD and co morbid symptoms and its long-term effects

EFT Testimony before Congress  Innovative Treatments for PTSD and TBI  House Veterans Affairs Committee  July 20, 2010  Iraq Veterans Stress Project  David Feinstein, PhD, Dawson Church, PhD,

and Wayne Miller  Research, Evidence Based, Rapid Results  Request for VA and DOD Implementation

EFT

JUST DO IT!

Q&A WITH PANEL

Closing Remarks Robin Tuohy, Vice President, Patient Support International Myeloma Foundation

Thank you to our speakers & our sponsors!

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OUR VISION:

A world where every myeloma patient can live life to the fullest, unburdened by the disease.

OUR MISSION:

Improving the quality of life of myeloma patients while working toward prevention and a cure.

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IMF Core Values:

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Patient Centric The patient experience is the focus of everything we do. Every interaction is an opportunity to establish a personal connection built on care and compassion which is the basis for continued support.

Respect All As a team, we value honesty and transparency while creating a culture of mutual respect. We foster a myeloma community built on sincerity, authenticity, and kindness.

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We respect the legacy and reputation of our organization while seeking new solutions and advancements to improve outcomes, quality of life, and access to the best available resources for everyone impacted by myeloma.

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