2024 Phoenix RCW Slide Deck by International Myeloma Foundation

Thank you to our sponsors!

What do the dots mean?

More than 1 year since diagnosis

Stem cell transplant recipient

Less than 1 year diagnosed

Care Partner for someone with Myeloma

9:00 – 9:15

9:10 – 9:20

IMF Regional Community Workshop

November 16th, 2024 - Agenda

Welcome & Introductions, Robin Tuohy, IMF Vice President, Patient Support

IMFs Strategic Direction, Yelak Biru, IMF President, CEO & 28-year Myeloma Patient

9:20 – 9:50 Myeloma 101, Dr. Saurabh Chhabra, Mayo Clinic - Arizona

9:50 – 10:00 Q&A with Panel

10:00 – 10:45 Taking the Reins of Your Multiple Myeloma Care, Beth Finley-Oliver, MSN, ARNP, AGNP-BC, H. Lee Moffitt Cancer Center, IMF Nurse Leadership Board Member

10:45 – 10:55 Q&A with Panel

10:55 – 11:05 Coffee Break

11:05 – 11:50 Frontline Therapy, Dr. Joseph Mikhael, IMF Chief Medical Officer

11:50 - 12:00 Q&A with Panel

12:00 – 12:10 Engage & Partner with the IMF, Sylvia Dsouza, IMF VP, Development

12:10 – 1:05 Lunch

IMF Regional Community Workshop

November 16th, 2024 – Agenda after the Break

1:05 – 1:25 Local Patient & Care Partner Panel, Gary Elliott (Patient) & Judy Elliott (Care Partner)

1:25 – 1:45 Maintenance Therapy, Dr. Joseph Mikhael, IMF Chief Medical Officer

1:45 – 1:55

1:55 – 2:40

2:40 – 2:50

Therapies & Clinical Trials, Dr. Saurabh Chhabra, Mayo Clinic – Arizona

Educational Publications

A core mission of the IMF is to provide thorough and cutting-edge education to the

Contact the InfoLine

Coordinators are available by:

• Email: Infoline@myeloma.org

• Phone – Live and returned calls (please leave a message if someone is not available to answer the call directly.)

• Scheduled visit: Use the link at Myeloma.org

Local Support Groups: You

Are Not Alone!

 Phoenix Multiple Myeloma Support Group

 Meets in-person on the 1st Thursday of each month at 10am MST

Find your local support group by scanning the QR code

 Tucson Multiple Myeloma Support Group

 Meets virtually on the 3rd Thursday of each month at 4pm MST

IMF – Special Interest Virtual Groups

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

 Las Voces de Mielomafounded in 2022

 For Spanish speaking patients

 Living Solo & Strongfounded in 2022

 For patients without a care partner

 Care Partners Onlyfounded in 2024

 Address the concerns of care partners

 MM Familiesfounded in 2021

 For patients & care partners with young children

 Veterans with Myelomacoming in 2025

 For those who serve our Country

 Smolder Bolderfounded in 2023

 For people living with Smoldering Multiple Myeloma

 High Risk Multiple Myelomafounded in 2023

 Addresses the needs of high-risk MM patients

EVALUATION

Please be sure to complete your program evaluation today.

Questions 1 – 5 can be completed before the program begins.

Questions 7 & 8 can be worked on after each presentation.

Our team will collect all responses at the end of the day!

We greatly appreciate your time and feedback!

IMFs Strategic Direction

Yelak Biru

IMF President, CEO & 28-year Myeloma Patient

Yelak Biru

28 Year Myeloma Patient

President and CEO

International Myeloma Foundation

Regional Community Workshop

Phoenix, AZ

A

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

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

Raise the Bar

Examine the why of all our actions to ensure they are purpose-driven, meaningful, and effective.

Guiding Principles

Broaden our Reach

Address unmet patient needs by expanding our reach to diverse & underserved populations in everything we do.

Innovate Every Step of The Way

Provide those who need it most with what they need the most, throughout their myeloma journeys.

Our Four Pillars

Sample of IMF Programs

Brian N. Jr/Sr Research Grant

International Myeloma Working Group

Nurse Leadership Board

Asian Myeloma Network

Latin America Myeloma Network

Global Myeloma Action Network

InfoLine 800-452 CURE (2873)

>150 Support Groups

Wellness Programs

SG Toolkit

RESEARCH

PATIENT

SUPPORT

Black Swan Research Initiative

I2 Team for Endpoint Approval of Myeloma MRD

Beyond Medicine Barriers

M-Power Peer Reviewed Publications Guidelines

Chart Studies

Clinical Trials

Patient & Family Seminars

Education

Regional Community Workshop Myeloma University

CME + NON-CME

Conference Series

Master Classes

Myeloma Made Simple

Podcasts | Blogs

Whitepapers

Videos | Publications

Coalition to Improve Access to Cancer Care Myeloma Action Team Veterans Against Myeloma All Access Congress

Events

Myeloma Action Month | Blood Cancer Awareness Month

IMF Programs That Accelerate Closing the Care Gap

Clinical Trials Matching

Engine:

Seamlessly matching patients to the latest clinical trials.

Existing IMF Programs That Accelerate this Initiative

Myelo:

The first generative AI Assistant designed specifically

The core vision of this initiative is to improve the short- and longterm outcomes of African American patients with myeloma. We want to empower patients and communities to change the course of myeloma…

Engage the community to increase awareness and provide support Shorten the time to diagnosis by educating primary care providers to recognize the disease and order the right tests

A Comprehensive, Global Patient Experience: Why It Matters

THE PROBLEM

PERSON A

Living with multiple myeloma in a wellresourced community:

• Diagnosed early by a trained provider

• Accesses state of the art therapies and enrolls in clinical trials at a major medical center

• Is connected to patient and family resources in their preferred language and support groups in their community that foster well being and promote efficacy of treatment

PERSON B

THE SOLUTION

A Comprehensive, Global Patient Experience.

Create a supportive, accessible, and personalized experience for all myeloma patients worldwide.

Living with multiple myeloma in an isolated or under-resourced community:

• Becomes very sick without diagnosis

• If diagnosed, might not learn about or have access to treatments or trials

• Does not have information about optimizing health while living with disease

• Does not have a community of support for navigating the disease

Leveraging IMF’s extensive resources, partnerships, and innovative technology, the program will empower patients by providing essential information, helping them navigate treatment options, and connecting them with comprehensive support.

Strategic Priorities

Collecting & Harnessing RealWorld Data

Addressing the World’s Most Critical Research Questions Providing a Comprehensive, Global Patient Experience

Myeloma 101 Saurabh Chhabra, MD, MS

Mayo Clinic, Arizona

Professor of Medicine, Mayo Clinic College of Medicine and Science

Division of Hematology/Oncology, Department of Medicine

Mayo Clinic, Phoenix, AZ 85054

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

• Appreciate the importance of health disparities in myeloma

How common is Myeloma?

Rate of New Cases per 100,000 Persons by Race/Ethnicity & Sex How common is Myeloma?

Percent of New Cases by Age

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

Multiple Myeloma Diagnosis Can Be Challenging

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

What

Causes Myeloma? How/Why Did I Get This?

Biochemical or Symptomatic Progression/Relapse

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

In most cases, the honest truth

WE DON’T KNOW

Bone Marrow Cells – Good & Bad

Hematopoietic stem cell

White Blood cell

Graphic Credit: Teresa Miceli

Platelets

Red Blood Cells

Plasma cell

Photo Credit

Clonal Plasma cells

(Mono)clonal Plasma Cells

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

Heavy Chain = M-Spike

cells

Spectrum of Monoclonal Protein Disorders

Condition MGUS1-4 (Monoclonal Gammopathy of Undetermined Significance)

1-5,8

Myeloma)

• AL-Amyloid

• POEMS

• Light or Heavy Chain Deposition Disease

• MGRS = Renal

• MGNS = Neuro

Presence of Myeloma Defining Events

Likelihood of progression

1. Kyle RA, et al. N Engl J Med. 2007;356:2582-90.

2. IMWG. Br J Haematol. 2003;121:749-57.

3. Jagannath S, et al. Clin Lymphoma Myeloma Leuk. 2010;10(1):28-43.

* In clinical trial

5. Mateos M-V, et al. Blood. 2009;114:Abstract 614.

6. Durie BG, Salmon SE. Cancer. 1975;36:842-854.

7. Durie BG, et al. Leukemia. 2006;20(9):1467-1473.

4. Kyle RA, et al. Curr Hematol Malig Rep. 2010;5(2):62-69.

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

Myeloma and Myeloma Defining Events

Testing For Myeloma: Blood & Urine

Test Name

CBC + differential

Complete metabolic panel

Beta-2 Microglobulin (B2M)

Lactate Dehydrogenase (LDH)

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)

What it means

Hemoglobin, WBC, Platelets

Creatinine, Calcium, Albumin, Liver function

Part of staging and risk stratification

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

This Photo by Unknown Author is licensed

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)

Healthy bone versus myeloma bone disease

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

Testing For Myeloma: Bone Marrow

Bone marrow genetics

• Cytogenetics

• Fluorescence in situ hybridization (FISH)

• Next generation sequencing (NGS)

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

Staging and Risk Stratification

Staging System (ISS) (only β2M and albumin)

Myeloma Treatment Schema

Transplan t Eligible Patients

Transplan t Ineligible Patients Consolidation / Maintenance Continued therapy Everyone

Supportive

Philippe Moreau. ASH 2015.

Drug Class Overview

(thalidomide)

(lenalidomide)

Drug Class Overview

Peptide Drug Conjugate*

BCMA Targeted Antibody Drug

Conjugate (ADC)*

Bispecific Antibodies

(Melphalan Flufenamide)

Blenrep (belantamab mafodotinblmf) Bela, Belamaf, or B

Abecma (idecabtagene vicleucel)

Carvykti (ciltacabtagene vicleucel)

Tecvayli (teclistimab)

Talvey (Talquetamab)

Elrexfio (Elranatamab)

Cevostamab, Iberdomide, Mezigdomide, Venetoclax

Linvoseltamab, LCAR-B38M, ABBV-383 ……………………………

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

Measuring Disease Response: IMWG Response Criteria

Negative by next generation flow (NGF) (minimum sensitivity 1 in 10-5 nucleated cells or higher)*

mCR AND normal Free Light Chain ratio, Bone Marrow negative by flow,

CR AND negative PCR

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

Very Good Partial Response: 90% reduction in myeloma protein

Partial Response: at least 50% reduction in myeloma protein

Minimal Response

Progressive Disease: At least 25% increase in identified myeloma protein from lowest level Stable Disease: Not meeting above criteria

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?

Biochemical or Symptomatic Progression/Relapse

• Not every relapse requires immediate therapy

• Each case is different

Symptomatic or extramedullary disease

Asymptomatic biochemical relapse on 2 consecutive assessments

Consider Treatment

Patient-/Disease-Specific Monitor Carefully

Asymptomatic high-risk disease or rapid doubling time or extensive marrow involvement Consider Observation Monitor Carefully

Initiate Treatment

Targets on the Myeloma Cell Surface and Therapeutic Antibodies

Bi-Specific Antibodies

Talquetamab

Antibody Drug

Elotuzumab

Bi-Specific Antibodies

Antibody Drug

Daratumumab and Darzalex Faspro Isatuximab

Immune Therapies

Ide-cel CAR-T

Cilta-cel CAR-T

Teclistamab

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

The Process of CAR T Cell Therapy

Relapsed MM with 4 prior LOT CAR T therapy recommended. Insurance approved and ready to move forward.

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

“Off the Shelf” Advantage

• No manufacturing process, unlike CAR T-cell 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). 2021;14(1):40.

The Evolution of Myeloma Therapy

Rev/Dex

CyBorD

D-VMP

DRD

D-VRD

Isa-VRD

D-KRD

Isa-VRD

Speaker’s own opinions. VD

Tandem ASCT (?)

Nothing

Thalidomide?

Bortezomib

Ixazomib

Lenalidomide

Combinations

“More” induction?

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; PDL1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib.

Bortezomib

Lenalidomide

Carfilzomib

Pomalidomide

Selinexor

Panobinostat

Daratumumab

Ixazomib

Elotuzumab Isatuximab

Belantamab mafodotin*

Melphalan flufenamide*

Idecabtagene autoleucel

Ciltacabtagene autoleucel

Teclistamab, Talquetamab

Elranatamab

CAR T Cell Therapy

Bispecific/Tri-specific Antibodies

Cell Modifying Agents

Venetoclax

PD/PDL-1 Inhibition?

Small Molecules

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

What about Disease Control and Cure in Myeloma?

Biochemical or Symptomatic Progression/Relapse

 Control is the immediate priority with active disease  Cure remains the overall goal

Defining “Cure” has many considerations:

Minimal Residual Disease Negative (MRD-)

Time Off Therapy

Functional Cure

Requiring Treatment Stable or Unmeasurable Disease, Receiving Treatment

Unmeasurable Disease, Receiving No Treatment Active Disease

https://seer.cancer.gov/statfacts/html/mulmy.html;

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

A Call to Action – Facts About African Americans and Myeloma

1.There is a longer time from symptoms to diagnosis among African Americans

2.African Americans are younger by about 5 years on average at diagnosis

3.MM and MGUS are more than 2x as common in African Americans

4.African Americans are less likely to receive the four T’s: Transplant, Triplets, Trials and CAR T

5.African Americans have biologic differences with more t(11;14) and less high-risk cytogenetics with deletion 17p

6.Survival outcomes in African Americans are HALF of what is seen in White Americans

7.African Americans can achieve equal or better outcomes when they receive therapy

provide

Q&A

Taking The Reins of Your Multiple Myeloma Care

Beth Finley Oliver, MSN, ARNP, AGNP-BC

H. Lee Moffitt Cancer Center and Research Institute & IMF Nurse Leadership Board member

STABLE OF TREATMENT

Myeloma and treatment options, side effects, symptom management, & supportive care

FINDING YOUR GAIT Know your care team & be an empowered patient GOING THE DISTANCE Healthful and meaningful living

Stable of Treatment

Treatment options, side effects, symptom management, and supportive care

Treatment Goals

Myeloma Therapies

• Rapid and effective disease control

• Durable disease control

• Improved overall survival

• Minimize side effects

• Promote good quality of life

Supportive Treatment

• Prevent disease- and treatmentrelated side effects

• Optimize symptom management

• Promote quality of life

Discuss your goals and priorities with your healthcare team.

Stable of Treatment Options

FRONTLINE

MAINTENANCE

Velcade® (bortezomib)

Ninlaro® (ixazomib)

Kyprolis® (carfilzomib)

RELAPSE

PENDING FDA

APPROVAL

Ninlaro® (ixazomib)

Darzalex® (daratumumab)

Sarclisa® (Isatuximab)

Darzalex® (daratumumab) in clinical trial

Darzalex® (daratumumab)

Empliciti® (elotuzumab)

Sarclisa® (Isatuximab)

Revlimid® (lenalidomide)

Thalomid® (thalidomide)

Revlimid® (lenalidomide)

Thalomid® (thalidomide)

Revlimid® (lenalidomide) Pomalyst® (pomalidomide)

Dexamethasone

Prednisone

Prednisolone

SoluMedrol

Immunotherapies

Dexamethasone

Prednisone

Prednisolone

SoluMedrol

Elrexfio™ (elranatamab)

Tecvayli® (teclistamab) Talvey™ (talquetamab)

Xpovio® (Selinexor)

Doxil (liposomal doxorubicin)

Iberdomide

Venclexta® (venetoclax):BCL2 inhibitor for t(11;14) Blenrep™ (belantamab mafodotin)*: antibody drug conjugate

Myelosuppression, GI

NOTED SIDE

Xpovio®: low sodium Blenrep™: eye-related

The Old Horse: Stem Cell Transplant

ELIGIBILITY

Measuring treatment response

Determining Transplant Eligibility

Insurance authorization

Collecting stem cells

TRANSPLANT

High Dose Chemotherapy, stem cell infusion

Supportive Care Engraftment

P H A S E 1 P H A S E 2 P H A S E 3

Duration: Approximately 2 weeks

Location: Transplant Center

Duration: Approximately 3-4 weeks

Location: Transplant Center

POSTTRANSPLANT

Restrengthening

Appetite recovery “Day 100” assessment

Begin maintenance therapy

Duration: Approximately 10-12 weeks

Location: HOME

CAR T: Another Treatment Approach

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

No driving for 8 weeks

“One & Done” with continued monitoring

T-Cell Collection

Manufacturing takes ≈ 4 to 6

Bridgingweekstherapy may be needed

• 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

Horse of Another Breed: 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)

BISPECIFIC ANTIBODIES

• GPRC5D target: potential for skin and nail side effects, GI issues of taste change, anorexia and weight loss

– Talvey™ (talquetamab)

CAR T and Bispecific Antibodies: Unique Side Effects

CRS is a common but often a mild & manageable side effect

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.

CAR T and Bi-specific Antibodies:

Side Effects

Neurotoxicity

is a rare but serious side effect

Steroids: The Good, The Bad, The Ugly

Steroids enhance the effectiveness of other myeloma therapies

Do not stop or alter your dose of steroids without discussing it with your provider

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

Steroid Side Effects

• Irritability, mood swings, depression

• Difficulty sleeping (insomnia), fatigue

• Blurred vision, cataracts

• Flushing/sweating

• Increased risk of infections, heart disease

• Muscle weakness, cramping

• Increased blood pressure, water retention

• Stomach bloating, hiccups, heartburn, ulcers, or gas

• Weight gain, hair thinning/loss, skin rashes

• Increased blood sugar levels, diabetes

Infection Can Be Serious for People With Myeloma

[P]reventing 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).

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)

Environmental control

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

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

As recommended by your healthcare team:

Immunizations:

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

Preventative and/or supportive medications (next slide)

Medications Can Reduce Infection Risk

Type of Infection Risk

Herpes virus reactivation (HSV/VZV); CMV reactivation Acyclovir prophylaxis

Bacteremia, pneumonia, and urinary tract infection

PJP (P jirovecii pneumonia)

Fungal infections (aspergillus)

Consider prophylaxis with levofloxacin

Consider prophylaxis with trimethoprim-sulfamethoxazole

Consider prophylaxis with fluconazole

Some people receiving BCMA-targeting therapies have experienced infections that are less common like CMV, PJP and fungal infections

Skin and Nail Side Effects

Possible side effects to some treatments and supportive care medications

Body Rash:

• Prevent dry skin; apply lotion

– Ammonium lactate 12% lotion

• Steroids:

– Topical for grades 1-2,

– Systemic and topical for Grade 3 and dose hold

• Antihistamines, as needed

Nail Changes:

FINDING YOUR GAIT

GOING THE DISTANCE

• Keep your nails short and clean. 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

Photos: Mount Sinai Hospital, NY, NY

Management of Oral Toxicities

STABLE OF

FINDING YOUR GAIT GOING THE DISTANCE

Taste Changes

Dry Mouth

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

OTC dry mouth rinse, gel, spray are recommended. Advise patients to avoid hot beverages. Preventative dental care and cleaning

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

Glossitis and Thrush

EARLY initiation of nystatin or Mycelex is key to manage symptoms.

• Weight loss and anorexia are associated with taste changes. Nutritionist involvement and dietary modifications are recommended to support patients. Appetite stimulant with Marinol, if indicated, can also be utilized.

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

Dysphagia

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.

GI Symptoms: Prevention &

Management

Diarrhea may be caused by medications and supplements

– Laxatives, antacids with magnesium

– Antibiotics, antidepressants, other (check with provider, pharmacist)

– Supplements: milk thistle, aloe, cayenne, saw palmetto, ginseng Management:

 Avoid caffeinated, carbonated, or heavily sugared beverages

 Take anti-diarrheal medication if recommended

 Bile Acid Sequestrants can reduce bile acid diarrhea

(Ex: cholestyramine, Colestid® (colestipol), Welchol® (colesevelam)

Constipation may be caused by medications and supplements

– 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

• Fruits, vegetables, high fiber whole grain foods

• Fiber binding agents – Metamucil®, Citrucel®, Benefiber®

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

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

Weight Management

Anorexia (difficulty eating)  Weight loss; Steroids  Weight gain

– Monitor weight for significant loss or gain

– Adjust diet (reduce calories or add supplements )

Pain Prevention and 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

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

• May include medications, activity, surgical intervention, radiation therapy, etc

• Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture, etc)

• Scrambler therapy for neuropathy

2017;21(5)suppl:19-36.

Sufficient Sleep: Important for Good Health

Adequate rest and sleep are essential to a healthful lifestyle

• Shortened and disturbed sleep cause

– Increased heart-related death

– Increased anxiety

– Weakened immune system

– Worsened pain

– Increased falls and personal injury

• Things that can interfere with sleep

– Medications: steroids, stimulants, herbal supplements

– Psychologic: fear, anxiety, stress

– Physiologic: sleep apnea, heart issues, pain

Sleep hygiene is necessary for quality nighttime sleep and daytime alertness

– Engage in exercise but not too near bedtime

– Increase daytime natural light exposure

– Avoid daytime napping

– Establish a bedtime routine - warm bath, cup of warm milk or tea

– Associate your bed ONLY with sleep

– Avoid before bedtime:

• Caffeine, nicotine, alcohol and sugar

• Large meals and especially spicy, greasy foods

• Computer screen time

– Sleep aid may be needed

Rod NH et al 2014. PloS one. 9(4):e91965; Coleman et al. 2011. Cancer Nurs. 34(3):219-227.National Sleep Foundation. At: http://sleepfoundation.org/ask-the-expert/sleep-hygiene Mustian et al. Journal of clinical Oncology. Sep 10 2013;31(26):3233-3241; Stan DL, et al. Clin J Oncol Nurs. Apr 2012;16(2):131-141; Zeng Y et al., Complementary therapies in medicine. Feb 2014;22(1):173-186.

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 sensation

• Muscle weakness

Prevention / management:

• Bortezomib once-weekly or subcutaneous administration

• Massage area with cocoa butter regularly

• Neuroprotective Supplements:

– B-complex vitamins (B1, B6, B12)

– Green tea

• Safe environment: rugs, furnishings, shoes

If neuropathy worsens, your provider may:

• Adjust your treatment plan

• Prescribe oral or topical pain medication

• Suggest physical therapy

Report symptoms of peripheral neuropathy early to your health care provider; nerve damage from neuropathy can be permanent if unaddressed

Understanding Changes to Kidney Function

• Risk Factors

– Active multiple myeloma (light chains, high calcium)

– Other medical issues (ex: Diabetes, dehydration, infection)

– Medications (MM treatment, antibiotics, contrast dye)

• Prevention

– Stay hydrated – drink water

– Avoid certain medications when possible (i.e., NSAIDs), dose adjust as needed

• Treatment

– Treatment for myeloma

– Hydration

– Dialysis

Many myeloma patients will experience kidney issues at some point; protecting your kidney function early and over time is important

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.

98.8% >35% of patients

Fatigue

Fatigue is the most commonly reported symptom.

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

≈25% of patients

Often, people do not share these symptoms with their provider. Talk to your provider about symptoms that are not well controlled or if you have thoughts of self harm. Help is available.

Additional Supportive Care

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.

Financial burden comes from • Medical costs – Premiums – Co-payments – Travel expenses – Medical supplies

• Prescription costs

• Loss of income

– Time off work or loss of employment

– Websites:

• Medicare.gov

• SSA.gov

• LLS.org

• Rxassist.org

– Caregiver time off work • Funding and assistance may be available – Federal programs, IRA & Medicare “Extra Help” – Pharmaceutical support – Non-profit organizations (TriageCancer.org)

• NeedyMeds.com

• HealthWellFoundation.org

• Company-specific website Contact the Social Services department at your hospital or clinic to talk to a social worker for assistance.

Finding Your Gait

Be an empowered patient; engage in your care

Don’t Ride Alone

YOU are central to the care team

Be empowered

• Ask questions, learn more

• Express your goals/values/preferences

• Ask for time to consider options Communicate with your team

• Understand the roles of each team member and who to contact for your needs

• Arrive at a treatment decision together Create a support network

Don’t Get Left in the Dust: Communicate How You Feel With Your Team

Unmanaged

Myeloma

can cause:

• Calcium elevation

• Renal dysfunction

• Low blood counts

• Infection Risk

• Blood clots

• Bone pain

• Neuropathy

• Fatigue

STABLE OF TREATMENT

FINDING YOUR GAIT GOING THE DISTANCE

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

How You Feel

Side Effects of Treatment can

cause:

• GI symptoms

• Renal dysfunction

• Low blood counts

• Infection Risk

• Blood clots

• Neuropathy

• Fatigue

IMF Videos

Going the Distance

Healthful and meaningful living

Care Partners Are Essential to Going the Distance

If you want to go fast, go alone, if you want to go far, go together

• Care partners may help in many ways including 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,

• 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

African Proverb

Form A Posse: Build Strong Social Ties & Cultivate a Sense

of Belonging

• Multiple studies demonstrate that strong social ties are associated with

– Increased longevity including people with cancer

– Improved adherence to medical treatment leading to improved health outcomes

– Lower risk of developing cardiovascular diseases

– Increased sense of purpose and life satisfaction

– Reduced stress and anxiety

– Improved mood and happiness

– Enhanced resilience

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.

• Strategies for enhancing social connection

– Deepen existing relationships with family, friends, and loved ones

– Build new relationships by participating in a support group, joining clubs or organizations, or volunteering

Tip: Start with small steps outside your comfort zone. Call a loved one you haven’t spoken to in a while.

Invite a person you’d like to know better for lunch, coffee, or a walk.

Hetherington C. Healthnews. https://healthnews.com/longevity/healthspan/social-connection-andlongevity/#:~:text=Research%20consistently%20demonstrates %20that%20people,of%20fulfillment%20in%20your%20life. Accessed Feb 1 2024.

Maintain Good Health

Have a Primary Care Doctor

Have Recommended Health Screenings

• Blood pressure

• Cholesterol

• Cardiovascular disease

• Dermatology (Skin)

• Diabetes

• Colonoscopy

• Vision

• Hearing

• Dental checkups & cleaning

• Women specific: mammography, pap smear

• Men specific: prostate

Maintain a healthy weight

• Good nutrition

• Activity or exercise

• Sufficient sleep

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.

Q&A

COFFEE BREAK

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation. We greatly appreciate your time and feedback!

Thank you to our sponsors!

Engage & Partner with the IMF

Sylvia Dsouza IMF VP, Development

Engaging & Partnering with the IMF

Sylvia Dsouza, Vice President, Development

 Vice President of Development for the IMF

WHO AM I? WHAT DO I DO?

 Securing philanthropic support and resources for the IMF through diverse mechanisms

 Oversee a team of passionate and determined fundraising professionals who are committed to advancing the mission of the IMF

 Have the incredible honor of working with dedicated volunteers from the US and across the globe.

3 Ways to Engage

Philanthropy

• Make a philanthropic gift to support research, education, advocacy or patient support programs.

• Organize or participate in fundraising events such as walks, runs, golf tournaments, community block parties, or galas.

• Create a fundraising campaign online to raise awareness and funds.

Volunteer

• Join your local support group/become a Support Group Leader

• Join our grassroots patient Advocacy program

• Volunteer your time at local races organized by the IMF to engage the community

• Engage on social media to connect with others affected by myeloma and spread awareness and empower patients with knowledge and resources.

Intellectual capacity

• Offer your expertise as a speaker or panelist at events.

• Be a beta tester for various new tools and products and provide reviews and feedback

Philanthropy Fuels Our Mission

Peer-to-Peer Fundraising

• Peer-to-Peer Fundraisers are created from YOUR ideas. Starting a Fundraiser is easy and fun. They also make a world of difference in the myeloma community.

• Engage your family, friends, co-workers, your network who honor your journey with myeloma and want to support you. Let them show you that you are not alone.

Join the HOPE Society (Recurring Monthly & Annual Giving Program)

• Help us cultivate the future by joining the International Myeloma Foundation's Hope Society.

• Monthly and annual gifts support IMF core programs, including educational events, publications, the toll-free InfoLine, and more.

• Start with a monthly contribution and when ready turn it into a yearly commitment. You will be a part of likeminded individuals united in the quest to find a cure for myeloma and a better quality of life for all myeloma patients.

Transformative Gifts (Major Giving and Principal Giving)

• Gifts can be designated toward a specific program, project or initiative .

• Is there something specific that resonates deeply with you and you want to see change happening?

• Gifts can also be unrestricted, expendable and/or an endowment

P2P

• Laughs 4 Life -- 8 years, $483,850!

Peer-to-Peer (P2P) and Monthly & Annual Giving

• Miracles for Myeloma -- 12 years, $804,422!

• Iceland Cycling Expedition-- Inaugural Event and opportunity to be a part of a group of patients, doctors, nurses to train together, bike across Iceland and raise money to support iStopMM cure trials.

• Hole In One – Inaugural golf tournament that has raised $73K

• Monthly & Annual Giving – HOPE Society

• Join our flagship monthly and annual giving program, the HOPE Society.

• Get invited to Regional Salon Dinners in your area with IMF leadership and KOLs.

• Receive exclusive updates on research and trials fresh off the press.

• Play a pivotal role in supporting our four pillars.

• Support long-term initiatives that make a lasting difference.

Major Giving - Black Swan Research Initiative

The Black Swan Research Initiative was funded by a Board member/donor who was a visionary and saw the need for the IMF to launch this initiative

The IMF's Black Swan Research Initiative serves as a conductor of sorts to this orchestra of collaborating experts in the field of myeloma.

The BSRI sponsors more than 50 projects around the world aimed at curing multiple myeloma. Among them:

SPAIN: The CESAR trial uses the combination of Kyprolis, Revlimid, and dexamethasone plus autologous stem-cell transplant to treat high-risk smoldering multiple myeloma. It applies: precise mininal residual disease (MRD) testing using next-generation flow cytometry (NGF) and Blood testing for routine monitoring

USA: The ASCENT trial tests early intervention in high-risk smoldering multiple myeloma.

ICELAND: Launched in 2016, the iStopMM project identifies and treats multiple myeloma at the earliest signs of disease.

GERMANY: Studies are exploring long-term survival and hereditary risk factors in multiple myeloma.

AUSTRALIA: Identifying mechanisms of the progression of multiple myeloma and t esting DNA mutations in the blood.

SINGAPORE: Hub for the clinical trials network in Asia led for the IMF’s Asian Myeloma Network (AMN) program by Prof Wee Joo Chng. A collaboration of eight countries (or regions), the AMN is unique in providing access to novel agents in a clinical trial setting throughout Asia. In addition, research projects appropriate for the region are conducted in an effort to improve outcomes and achieve a cure.

What will your legacy be?

Planned Giving

• Join the Brian D. Novis Legacy Society and make a planned gift!

• Gain immediate tax benefits

• Potentially increase your income during your lifetime.

• Continue to fund our core programs and four pillars.

• Make a bequest (a gift from your estate)

• Include a provision in your will or living trust.

• Designated us as a beneficiary of a life insurance policy, or retirement plan (IRA, 401(k), or 403(b).

• Leave us in your will is one of the most profound ways to support the people and causes important to you.

Corporate and Foundation Gifts

• Your organization can contribute a corporate gift or foundation grant

• Provide seed funding that is necessary to accelerate the path to a cure.

We reached our goal of $250,000! ( we are over $273K)

• You all helped us do this - THANK YOU!

Support Group Leaders Summit 25th Anniversary

"The Support Group Leaders Summit has empowered me to network with leaders nationwide, learn from their experiences, and appreciate the dedication of the International Myeloma Foundation (IMF) to patients, caregivers, and families affected by myeloma."

Start the Conversation

We welcome you to continue to learn more about our programs, projects, and initiatives at the IMF and find alignment with your own myeloma journey as well as ways to deepen and strengthen your engagement with us. Reach out to the IMF Development Team to start a conversation on how you can make a difference in the lives of the people impacted by myeloma.

Sylvia Dsouza Vice President, Development sdsouza@myeloma.org (310) 947.4126

Kimberly Francis Assistant Director, Peer-to-Peer Fundraising kfitzpatrick@myeloma.org (818) 487-7455 x304

Matthew Broughton Assistant Director, Operations mbroughton@myeloma.org (818) 487-7455 x299

QUESTIONS?

Frontline Therapy Joseph Mikhael,

MD, MEd, FACP, FRCPC

IMF Chief Medical Officer

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

Treatment

>1 Billion

>1 Trillion D i s e a s e B u r d e n ( # o f m y e l o m a c e l l s )

>10 Million

1 myeloma cell in 100K to 1 million normal cells

Symptomatic Myeloma

At diagnosis

Partial response

50% reduction in M protein

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

DEPTH

Biran N, et al. Curr Hematol Malig Rep 2014;9:368–78

MRD is Prognostic – Both for PFS and OS

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

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, Personal Preference ASCT Eligible ASCT Ineligible ASCT = Auto Stem Cell Transplant

General Principles of Initial Therapy

1. Most patients will be given a combination of drugs to control the disease quickly

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 transplant

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 FDA approved THIS year!!

• Transplant Eligible

• Darzalex-Velcade-Revlimid-Dexamethasone (PERSEUS)

• Transplant Ineligible

• Sarclisa-Velcade-Revlimid-Dexamethasone (IMROZ)

• Sarclisa-Velcade-Revlimid-Dexamethasone (BENEFIT)

• Darzalex-Velcade-Revlimid-Dexamethasone (CEPHEUS)

PERSEUS: Study Design

Induction

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

Consolidatio

VRd administered as in the VRd group

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.

PERSEUS: Progression-free Survival

PERSEUS: Overall CR Rates

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

143/205 (69.8) 105/149 (70.5)

186/267 (69.7) 62/87 (71.3)

226/323 (70.0) 22/31 (71.0)

129/178 (72.5)

84/125 (67.2) 34/50 (68.0)

122/185 (65.9) 73/96 (76.0)

182/266 (68.4) 59/78 (75.6) 7/10 (70.0)

160/230 (69.6) 88/124 (71.0)

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

(90.0)

(81.9)

(87.6)

(92.0)

(89.8)

(88.6)

(80.0) 178/204 (87.3) 72/78 (92.3)

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

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

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

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

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

1Department of Haematology, University of Lille, and French Academy of Medicine, Paris, France; 2Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Greece; 3Service 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.

ID #OA-49

Study design: Isa-VRd vs VRd in transplant-ineligible NDMM

Initiation phase (4

Treatment until PD, unacceptable toxicities, patient withdrawal

Primary endpoint: PFS

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

(bone marrow aspirate)

In case of CR or VGPR

*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.

Baseline characteristics

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

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

60-mo PFS rate: 63.2% mPFS: NR

60-mo PFS

45.2% mPFS: 54.34 months (95% CI, 45.207 to NR)

*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.

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

†Cycle 1 only. CR,

PRESENTED BY: Xavier Leleu, MD, PhD

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.

Dr. Joe Commentary

• 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 – don’t need 25mg in most patients

• Velcade – should be given weekly – still unclear as to length of time

• Dexamethasone – DOWN with DEX!

HISTORICAL TREND TOWARD OPTIMAL DEXAMETHASONE DOSING

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

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

End Points of Study and Follow-up

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

• 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

Primary Endpoint: Progression-Free survival (PFS)

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

1.53 (1.23–1.91), p<0.0001

Key secondary endpoint: Overall survival (OS)

Median follow-up 76 months Data cut off:12/12/21

*p-value adjusted using Bonferroni’s correction to control overall family-wise error rate for secondary outcomes

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:

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 – Discussant DETERMINATION

Will MRD guide us to stop therapy?

MASTER Trial - Treatment

Dara-KRd

• Daratumumab 16 mg/m2 days 1,8,15,22 (days 1,15 C 3-6; day 1 C >6)

• Carfilzomib (20) 56 mg/m2 Days 1,8,15

• Lenalidomide 25 mg Days 1-21

• Dexamethasone 40mg PO Days 1,8,15,22

MRD assessment by NGS

Progression-Free and Overall Survival

How do we decide who is eligible for transplant?

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

Recommendation

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

Evidence Rating

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.

MAIA Study Design – DRD vs RD

Patients were enrolled in MAIA from March 2015 through January 2017

D: 16 mg/kg IV

QW Cycles 1-2, Q2W Cycles 3-6, then Q4W thereafter until PD

Primary endpoint

Key eligibility criteria

• TIE NDMM

• ECOG PS

score 0-2

• CrCl

≥30 mL/min

R: 25 mg PO Days 1-21 until PD

da: 40 mgb PO or IV Days 1, 8, 15, 22 until PD

End-oftreatment visit (30 days after last dose) Longterm follow-up

• PFS Key secondary endpoints

• OS

• PFS2

• ORR

• MRD (NGS; 10–5) 1

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

Cycles: 28 days Rd

• CR/sCR rate

Updated PFS

• D-Rd continued to demonstrate a significant PFS

• These data provide a new PFS benchmark in patients with

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

Conclusions

• We still do not generally treat smoldering myeloma

• 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

MSMART: Newly Diagnosed Transplant Eligible

Standard Risk

Dara-VRd or Isa-VRd x 3-4 cycles

Early ASCT

Cryopreserve stem cells and continue induction x 58 cycles

High Risk

Dara-VRd or Isa-VRd x 3-4 cycles

Early ASCT

Lenalidomide maintenance

Bortezomib plus Lenalidomide maintenance

MSMART: Newly Diagnosed Transplant Ineligible

Standard Risk

High Risk

Not Frail

Not Frail Frail

VRd x 8-12 cycles and lenalidomide maintenance, or DRd

Dara-VRd or IsaVRd 8-12 cycles and lenalidomide maintenance

VRd x 8-12 cycles and lenalidomide plus bortezomib maintenance

Dara-VRd or IsaVRd 8-12 cycles and lenalidomide plus bortezomib maintenance

The Evolution of Myeloma Therapy

Bortezomib

Lenalidomide

Carfilzomib

Pomalidomide

Lenalidomide

Bortezomib

Ixazomib

Lenalidomide + PI

SCT +/- More induction

D-KRD

Isa-KRD

Isa-VRD

New

D-KRD CAR T or Bispecifics?

Carfilzomib

Combinations

Selinexor

Panobinostat

Daratumumab

Ixazomib

Elotuzumab

Isatuximab

Idecabtagene autoleucel

Ciltacabtagene autoleucel

Teclistamab

Talquetamab

Elranatamab

ASCT,

Daratumumab?

Novel CAR T Cell Therapies

Bispecific/Trispecific Antibodies

CelMod Agents

Venetoclax?

Belantamab soon?

Multiple small molecules ++++++++

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.

Q&A

LUNCH BREAK

November 16th, 2024 – Agenda after the Break

1:05 – 1:25

Patient & Care Partner Panel, Gary Elliott (Patient) & Judy Elliott (Care-Partner) 1:25 – 1:45

EVALUATION

Please take a moment to reflect and respond to the program evaluation.

Questions 7 & 8 can be worked on after each presentation.

We greatly appreciate your time and feedback!

Thank you to our sponsors!

Local Patient & Care Partner

Gary & Judy Elliott

Maintenance Therapy

Joseph Mikhael, MD, MEd, FACP,

FRCPC

IMF Chief Medical Officer

Objectives

• Discuss the principle of consolidation therapy and its application in myeloma

• Outline the major options for maintenance therapy

• Introduce the newer trend for the use of dual maintenance

• Provide an algorithm for maintenance based on risk status

Understanding the Terms

• Induction: Intense and short-term therapy with goal to achieve rapid remission

• Consolidation: Intense and shorter-term therapy with goal of deep remission

What does the Ideal Maintenance therapy look like?

• Deepen remission

• Prolong remission

• Easy to administer

• Minimal toxicity

• Maintenance: Less intense longer-term therapy with goal of better PFS and OS

Maintenance Therapy with Revlimid (lenalidomide) is the standard of care

It is usually given 10-15mg per day for 21/28 days

• This is based on several studies

• French trial of no maintenance vs Revlimid for 2 years (IFM2005-02)

• American trial of no maintenance vs Revlimid until progression (CALBG 100104)

• British trial of no maintenance vs Revlimid until progression came later

Meta-Analysis of Lenalidomide Maintenance after ASCT

CALGB 100104

(accrual 8/2005 – 11/2009)

INDUCTION

ASCT

1:1 RANDOMIZATION

“NO EVIDENCE OF PD”

Primary Endpoint: PFS

IFM 2005-02

(accrual 6/2006 – 8/2008)

INDUCTION

ASCT

1:1 RANDOMIZATION

“NO EVIDENCE OF PD”

Primary Endpoint: PFS

LEN: 2 COURSES

GIMEMA (RV-MM-PI-209) (accrual 11/2007 – 7/2009)

2 × 2 DESIGN

LEN + DEX × 4 INDUCTION

Primary Endpoint: PFS

MPR: 6 COURSES

LEN MNTCa (n = 231) PLACEBO (n = 229)

PLACEBO (n = 307)

LEN MNTCa (n = 307)

INTERIM AN Dec 2009 Jan 2010

INTERIM ANALYSIS AND UNBLINDING

CROSSOVER BEFORE PD ALLOWED CONTINUED TREATMENT

TREATMENT NO CROSSOVER BEFORE PD ALLOWED

ALL TREATMENT DISCONTINUED Jan 2011 CONTINUED

LEN MNTCb (n = 67) NO TREATMENT (n = 68) LEN MNTCb NO TREATMENT ASCT CONTINUED TREATMENT CONTINUED TREATMENT PRIMARY ANALYSIS

Target population of patients with NDMM who received LEN maintenance or placebo/no maintenance after ASCT

a Starting dose of 10 mg/day on days 1-28/28 was increased to 15 mg/day if tolerated and continued until PD.

b Patients received 10 mg/day on days 1-21/28 until PD.

ASCT, autologous stem cell transplant; LEN, lenalidomide; NDMM, newly diagnosed multiple myeloma; MNTC, maintenance; MPR, melphalan, prednisone, and Len; PD, progressive disease.

Key Results of Initial Meta-Analysis

randomized trials: 1,209 patients:

• Median follow up 6.6 years

• PFS 52.8 months for lenalidomide vs 23.5 in placebo

• PFS2 also prolonged 73.3 months vs 56.7 (i.e. not creating more aggressive clone)

• Median overall survival: 86 months v. not reached: P = 0.001

• Benefit for ≤ PR as well as VGPR/CR patients

• 29% discontinuation rate with lenalidomide

• Second primary malignancy rate higher at 6.1% vs 2.8% in placebo after PD

Myeloma XI

Induction

Maintenance

Lenalidomide

10 mg/day, days 1‒21/28

N=1551 (TE=828; TNE=723)

Median follow-up: 27 months (IQR 13‒43)

Exclusion criteria

• Failure to respond to lenalidomide as induction IMiD, or development of PD

• Previous or concurrent active malignancies

Treated on Myeloma XI induction protocols IQR, interquartile range; NDMM, newly diagnosed multiple myeloma; PD, progressive disease

Observation

Overall PFS

Significant improvement in PFS from 18 to 36 months, HR=0.45

Lenalidomide (n=857) 36 [31, 39]

Observation (n=694) 18 [16, 20]

But can we do better than lenalidomi de alone?

FORTE Trial design