IMF Patient and Family Seminar — Boca Raton, FL

2023 Boca Raton Patient and Family Seminar

March 17 & 18, 2023

Thank you to our Sponsors!

Taking The Reins of Your Multiple Myeloma Care

Beth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO

Cleveland Clinic Taussig Cancer Institute, IMF

Nurse Leadership Board Member

Beth Faiman PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO

Clinic, Cleveland, OH USA

Objectives

STABLE OF TREATME

FINDING YOUR GAIT

ENJOYING THE RIDE

STABLE OF TREATMENT

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

FINDING YOUR GAIT

• Know your care team, telehealth & meeting prep, & shared decision making

GOING THE DISTANCE

• Healthful living, infection prevention, renal and bone health

Stable of Treatment

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

Gallery of Goals

Myeloma Treatment

• Prevent disease- and treatment-related side effects

• Optimize symptom management

• Allow for good quality of life

Supportive Therapies

• Rapid and effective disease control

• Durable disease control

• Improved overall survival

• Minimize side effects

• Allow for good quality of life

Discuss goals and priorities with your healthcare team.

Myeloma Therapy Combinations

Myeloma Treatment Pallet Common Combinations

Velcade® (bortezomib) VRd, Vd

Revlimid® (lenalidomide) VRd, Rd

Kyprolis® (carfilzomib) KRd, Kd, DKd, Isa-Kd

Pomalyst® (pomalidomide) Pd, DPd, EPd, PCd, Isa-Pd

Darzalex® (daratumumab) DRd, DVd, DPd, DVMP, DKd

Ninlaro®(ixazomib) IRd

Empliciti® (elotuzumab) ERd, EPd

Tecvayli (teclistimab --

Xpovio® (Selinexor) Selinexor-Vd, Selinexor-dex

Sarclisa® (Isatuximab) Isa-Kd, Isa-Pd

Blenrep® (Belantamab mafodotin) Bela-d

ABECMA ® Idecabtagene Vicleucel, CARVYTKI ® ciltacabtagene autoleucel --

Venclexta® (venetoclax) Vd + ven

New agents or regimens in clinical trials are always an option

Don’t change horses midstream

It is important to stay on myeloma treatment to control myeloma cells and get the most from each treatment.

Responses deepen over time.

Talk to your team if side effects are bothersome. Your team may be able to help but only if they know.

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I = ixazomib; K = carfilzomib; M = melphalan; P = pomalidomide; R = lenalidomide; V = bortezomib; ven = venetoclax *Withdrawn from FDA but still available in certain situations . Prescribing information for each drug listed in the table. NCCN Guidelines. Multiple Myeloma. V3.2023. Accessed January 13, 2023.

Additional Options to Address Side Effects

Non-medication

Patient-Reported Symptoms

A meta-analysis identified the most common patient-reported symptoms and their impact on QOL. Symptoms were present at all stages of disease. Symptoms resulted from both disease and treatment, including transplant, and were in these categories:

Physical

• Fatigue

• Constipation

• Pain

• Neuropathy

• Impaired Physical Functioning

• Sexual Dysfunction

Ramsenthaler, et al. 2016. https://doi.org/10.1111/ejh.12790.

Psychological

• Depression

• Anxiety

• Sleep Disturbance

• Decreased Cognitive Function

• Decreased Role & Social Function

Financial

• Financial burden (80%)

• Financial toxicity (43%)

Steroids: The Good, The Bad, The Ugly

Steroid Synergy

• Steroids are a backbone and work in combination to enhance myeloma therapy

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

GI Symptoms: Prevention & Management

Diarrhea may be caused by medications and supplements

• Laxatives, antacids with magnesium

• Antibiotics, antidepressants, others

• Milk thistle, aloe, cayenne, saw palmetto, ginseng

• Sugar substitutes in sugar free gum

Avoid caffeinated, carbonated, or heavily sugared beverages

Take anti-diarrheal medication if recommended

• Imodium®, Lomotil®, or Colestid® or Welchol®

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

Constipation may be caused by medications and supplements

• Opioid pain relievers, antidepressants, heart or blood pressure medications

• 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®

Fluid intake can help with both diarrhea and constipation and helps kidney function. Discuss GI issues with health care providers to identify causes and make adjustments to medications and 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; anti viral to prevent shingles; sedation before procedures

– Interventions depends 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

Tell your health care provider about any new bone pain or chronic pain that is not adequately controlled.

Peripheral Neuropathy Management

Peripheral neuropathy:

Damage to nerves in extremities (hands, feet, or limbs)

• 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

• Supplements:

– B-complex vitamins (B1, B6, B12)

– Folic acid, and/or amino acids but do not take on day of Velcade® (bortezomib) infusion

• Safe environment: rugs, furnishings, shoes

If neuropathy worsens, your provider may:

• Change your treatment

• 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.

Why the Long Face?

98.8%

Fatigue is the most commonly reported symptom. Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression

>35% of patients

~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.

Rest and Relaxation Contribute to Good Health

• Adequate rest and sleep are essential to a healthful lifestyle

– Shortened and disturbed sleep increase risk of

– Heart related death

– Increase anxiety

–

Weakened immune system

–

Worsened pain

–

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

• Sleep aid may be needed

– Avoid before bedtime:

• Caffeine, nicotine , alcohol and sugar

• Large meals and especially spicy, greasy foods

• Computer screen time

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.

Financial Burden

• 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

–

Caregiver time off work

• Funding and assistance may be available

–

Federal programs

–

Pharmaceutical support

–

Non-profit organizations

– Websites:

• Medicare.gov

• SSA.gov

• LLS.org

• Rxassist.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

Know your care team, telehealth & meeting prep, & shared decision making

Don’t Ride Alone

YOU are central to the care team

Be empowered

• Ask questions, learn more

• Participate in decisions

Primary Care Provider (PCP)

Communicate with your team

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

• Participate in support network

Subspecialists

General Hem/Onc

Myeloma Specialist

You and Your Caregiver(s) Support Network

Prepare for Visits and Consider Telemedicine

Come prepared

 Bring a list of current medications, prescribed and over the counter

 Write down your questions and concerns. Prioritize them including financial issues

 Have there been any medical or life changes since your last visit?

 Current symptoms - how have they changed (improved, worsened, stable)? Keep a symptom diary. Bring it along

 Communicate effectively: your health care team can’t help if they don’t know

 Know the “next steps”, future appointments, medication changes, refills, etc

Check with your healthcare team –

Is telemedicine an option?

• Similar planning for “in-person” appointment PLUS:

 What is the process and what technology is needed?

 Plan your labs: are they needed in advance? Do you need an order?

 Plan your location: quiet, well-lit location with strong wi-fi is best

 Plan yourself: consider if you may need to show a body part and wear accessible clothing

 Collect recent vital signs (blood pressure, temp, heart rate) self-serve blood pressure cuff is available at many pharmacies and for purchase

Shared Decision-Making

Be empowered to be part of the treatment decision-making

• Ask for time to consider options (if needed/appropriate)

• Understand options; consider priorities

– Use reliable sources of information

– Use caution considering stories of personal experiences

– Consider your goals/values/preferences

• Express your goals/values/preferences; create a dialog

–

My top priority is [goal/value]; additional [preferences] are also important.

–

I think [treatment] may be a good choice given my priorities… What do you think?

• Arrive at a treatment decision together

Going the Distance

Healthful living, infection prevention, renal and bone health

Healthful Living Strategies: Prevention

Maintain renal health

• Myeloma management

• Hydration

• Avoid renally-toxic medications

– Dose adjust to renal function

• Diabetes management

Protect your bones

• Nutrition, Calcium + D supplement

• Weight-bearing activity and/or walking

• Bone strengthening agents

Manage stress

• Rest, relaxation, sleep hygiene

• Mental health / social engagement

• Complementary therapy

Preventative health care

• Health screenings, vaccinations

• Prevent falls, injury, infection

• Stop smoking

• Dental care

Maintain a healthy weight

• Nutrition

• Activity / exercise

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.

Infection Awareness & Prevention

Infection Prevention Tips

Good personal hygiene (skin, oral)

Environmental control (wash hands, avoid crowds and sick people, etc)

Growth factor (Neupogen [filgrastim])

Immunizations (NO live vaccines)

Medications (antibacterial, antiviral)

As recommended by your health care team

COVID: The Best Way to Prevent Illness Is to Avoid Being Exposed to the Virus

Spread mainly through respiratory droplets that are produced by cough, sneezing and talking. More droplets with louder talking, yelling, singing

• Get COVID Vaccine + Booster: Excellent protection against severe disease, but vaccine effectiveness may be lower in people with compromised immune systems

• Wear a High-quality Mask: Respiratory droplets can spread disease; a high-quality mask can prevent exposure to airborne viral particles

• Avoid Crowds & Sick People

• Physical Distance & Outdoors: Close contact and indoor locations increases risk of spread

• Wash Your Hands: Less common to get from a hard surface

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

• Compromised immune function comes from multiple myeloma and from treatment.

• Infection is serious for myeloma patients!

Healthful Living Strategies: Keep Active

Movement therapies can reduce stress, promote sleep

Yoga, Pilates, Tai Chi

• Shown to improve sleep and sleep quality

• Improved quality of life & mood

Do:

• Keep a log or journal of your activity

• Notify your healthcare provider about sudden onset of pain, progressive weakness, headaches, blurred vision, numbness, and tingling

• Dehydration can lead to low blood pressure, falls

• Consider weightlifting limits

Do Not:

• Overdo it

• Force exercise

• Try things without discussing with provider Boullosa

Myeloma bone disease may affect your ability to do certain movement activities. Review your activity interests with your health care provider!

Don’t Put the CAR T Before the Horse: CAR T cell therapy, Bi-specific Antibodies, and Clinical Trials in Multiple Myeloma

Stable of Goals

Myeloma Treatment

• Rapid and effective disease control

• Durable disease control

• Minimize side effects

• Allow for good quality of life

• Improved overall survival

Supportive Therapies

BI - SPECIFIC ANTIBODIES

CLINICAL TRIALS

• Prevent disease- and treatmentrelated side effects

• Optimize symptom management

• Allow for good quality of life

Discuss goals and priorities with your healthcare team.

CAR T: A New Treatment Approach

STABLE OF TREATME

CAR T CELL THERAPY

FINDING YOUR GAIT

BI - SPECIFIC ANTIBODIES

ENJOYING THE RIDE

CLINICAL TRIALS

CAR T: Tips

• Different CAR T-cell therapy products have differences in efficacy, safety, manufacturing process, and centers where they are available

• Ask for a referral to CAR T-cell therapy center as soon as it is possible as next treatment option (ie, before relapse)

– Insurance preauthorization required (weeks, maybe longer)

– Must have sufficient blood count and organ function to be eligible

• Your own T cells are engineered and grown, which takes ≈ 4 to 6 weeks

– Must be able to wait or have bridging therapy

– Manufacturing CAR T-cell therapy is limited: center-specific “wait list” processes

• Need to be “known” by the center. How frequently do you or your myeloma doctor need to check in with the CAR T center to let them know your status? How will this happen?

Opportunity for telehealth visits?

• How are slots allocated?

• Advocate for yourself—ask for help navigating the process

• In patient for ~1 week when CAR T administered

• Patients need a caregiver and must stay within proximity of CAR T-cell therapy center for ≈ 1 month after the infusion

• No driving for 8 weeks after CAR T

• One and done…BUT will need ongoing monitoring; some patients need transfusion support

Horse of Another Color:

BiSpecific Antibodies also Target BCMA

• Different bispecific antibodies have differences in efficacy, side effects

– About 7 in 10 patients responded

– CRS is common

– Some had skin/nail disorders

• Tecvayli™ (teclistamab) is the first but more expected

• Off-the-shelf treatment; no waiting for engineering cells

• Infusion (every 2 weeks by may vary)

• CRS, Neurotoxicity, infection are possible

BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; MM = multiple myeloma; scFV = single chain fragment variable.

CAR

THERAPY

CLINICAL TRIALS

BISPECIFIC ANTIBODIES

Cytotoxic cytokines

BCMA CD3

CAR T and Bi-specific Antibodies: Unique Side Effects

CRS is a common but usually mild side effect

CAR T and Bi-specific Antibodies: Unique Side Effects

Seizures

Neurotoxicity is a rare but serious side effect

Clinical Trials: Early Access to Promising Treatments

Pre-clinical

ANIMAL STUDIES FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS

Phase 1

• Determine metabolism and PK/PD actions, MTD, and DLT

• Identify AEs

• Gain early evidence of effectiveness, studied in many conditions; typically, 20 to 80 patients; everyone gets agent

Phase 2

EVALUATION OF EFFECTIVENESS IN A CERTAIN TUMOR TYPE

• Determine short-term AEs and risks; closely monitored

• Includes up to 100 patients, typically

Phase 3

GATHER ADDITIONAL EFFECTIVENESS AND SAFETY INFORMATION COMPARED TO STANDARD OF CARE

• Placebo may be involved if no standard of care exists; 100s to several thousand patients

• Often multiple institutions; single or double blind

Phase 4

APPROVED AGENTS IN NEW POPULATIONS OR NEW DOSE FORMS

AE = adverse event; DLT = dose-limiting toxicity; MTD = maximum tolerated dose; PD = pharmacodynamics; PK = pharmacokinetics.

Oncol. 2016;7:17-29.

FINDING

How to Find Clinical Trials

Clinicaltrials.gov

https://clinicaltrials.gov/

IMF Infoline

CLINICAL TRIALS

ENJOYING THE RIDE

US & Canada 800-452 CURE (2873)

Worldwide: 1-818-487-7455

infoline@myeloma.org

Clinical Trial Myths: Dispelling Inaccuracies

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

BI - SPECIFIC ANTIBODIES CLINICAL TRIALS

• 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: Patients (whatever demographic/ distance from clinic/etc) never participate in clinical trials so I won’t mention it

• Mention the option and give the patient the opportunity; implicit and explicit biases can limit participation

• Some groups may need more information about clinical trials to feel comfortable with participation

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 though 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 may not be reimbursed and are paid by patient

Importance of Diversity in Clinical Trials

People from racial and ethnic minority 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.

Regnante JM, et al. J Oncol Pract. 2019;15(4):e289-e299. FDA website. Clinical Trial Diversity. Accessed March 31, 2022. https://www.fda.gov/consumers/minority-health-and-health-equity/clinical-trial-diversity. International Myeloma Foundation website. Accessed March 31, 2022. https://www.myeloma.org/node/4797.

Nurse Leadership Board

In 2006, the IMF founded the Nurse Leadership Board® as a professional partnership to represent oncology nurses who are experts in the care of multiple myeloma patients at leading medical centers. The NLB is improving the nursing care and self- care of patients with multiple myeloma via publications, symposia, multimedia, and research.

Disparities in Myeloma Joseph Mikhael,

MD

International Myeloma Foundation

Health Disparities in Myeloma

Boca Raton Patient and Family Seminar

March 17, 2023

Dr. Joseph Mikhael Chief Medical Officer

International Myeloma Foundation

• A word of caution when we discuss issues of Diversity, Equity and Inclusion…

• Personal, Professional and Political

• Equity means to guarantee of fair treatment, access, opportunity, and advancement for all while striving to identify and eliminate barriers that have prevented the full participation of some groups.

• Valuing diversity means that we recognize and respect everyone’s unique qualities and attributes.

• Inclusion means that all individuals feel respected, accepted and valued.

• The history of the IMF compels us to continue to advocate for all

What are Health Disparities?

• Health disparities are preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations - Centers for Disease Control (CDC)

• Health equity generally refers to individuals achieving their highest level of health through the elimination of disparities in health and health care

1. Systemic racism

2. The Healthcare system

3. Social Determinants of Health

4. Biology of the disease and concomitant comorbidities

5. Delayed Diagnosis

6. Access to Care – Triplets, Transplants, Trials and Car T

7. Lack of diversity, cultural sensitivity and optimal communication in healthcare professionals

What are the DRIVERS of Disparities in MM?

What are the FACTS about Disparities in MM?

Multiple myeloma is one of the malignancies with the greatest disparity in incidence and prevalence between African Americans and White Americans. It is the most common blood cancer in African Americans (twice the incidence than White Americans). The average age of diagnosis is 4-5 years younger in African Americans and Hispanic Americans

Studies show that biologic differences in myeloma in African Americans may lead to lower-risk disease whereas there may be more high risk disease in Hispanic Americans. African Americans and Hispanic Americans are less likely to receive life-extending therapies. Mortality is TWICE as high in African Americans with myeloma than White Americans

African Americans achieve equal or better outcomes compared to White Americans when they receive therapy.

Ailawadhi et al. (2012); Baker et al. (2013); Greenberg et al. (2015); Hari et al. (2010); Rhotagi et al. (2007); Saraf et al. (2013); Waxman et al. (2010); Data derived by calculating the ratio of the average African American to white age - adjusted incidence rates from 2000 - 2013 for the 8 most common malignancies in African Americans, plus all cancer sites and multiple myeloma. Incidence rates were obtained from: National Cancer Institute. Fast stats. Surveillance, Epidemiology,

1. Myeloma is

in African Americans And the incidence is

the most common blood cancer

growing….

By 2034 it is estimated that African Americans will make up roughly 24% of the newly diagnosed MM population1

2. Myeloma is TWICE as common in African Americans

African Americans have >2x the incidence rate of MM compared to white Americans1

1. American Cancer Society. Cancer Facts and Figures for African Americans 2019-2021.

3. African Americans are younger at diagnosis by about 5 years

Hispanic African American Asian White

66 65

71 69 YEARS YEARS YEARS YEARS

The median age at diagnosis for all patients is 69 years

4. African Americans comprise about 20% of all patients with MM

Currently, African Americans comprise 14% of the total population of the USA

Mortality is TWICE as high in Black Americans with myeloma

6. There is a LONGER time from symptom onset to diagnosis in African Americans

The average myeloma patient sees their primary care doctor THREE times with symptoms and signs consistent with MM. The delay is even longer in African Americans, for many reasons:

Confounding diagnoses (like diabetes)

Access to diagnostics and care

Awareness in primary care providers

Timely referral to specialists…

8. African Americans are much less likely to participate in Clinical Trials (the 4th T)

Blacks/African Americans and Myeloma Clinical Trials

Blacks/African Americans are underrepresented in clinical trials, including Myeloma trials. Blacks/African Americans represent 15% of the general cancer population; however, only comprise 4-6% of trial participants.

Blacks/African American myeloma patient enrollment steadily increased in the early 1990s, then began to decline in the early 2000s.

Underrepresentation of Blacks/African Americans in clinical trials can limit the generalization and validity of the findings of the clinical trial.

9. There are biologic differences in African Americans with MM that may lead to lower risk disease

African ancestry associated with less aggressive disease

Higher prevalence of [a]:

t(11;14) t(14;16) t(14;20)

Lower prevalence[c]:

13q deletion

17p deletion

• Absence of 17p deletion associated with better survival among younger African Americans vs White counterparts[d]

10. When African Americans receive equal access to care, their survival outcomes are equal, and at times, better than Whites

Fillmore NR, et al. Blood. 2019;133:2615-2618

So what can we do about this?

• It is a complex problem and requires a complex solution

• Key themes of Success:

• Awareness, Education, Advocacy and Empowerment in the lay community

• Education, Cultural Competence, Access in the medical community

• Policy, Expectations, Commitment in the regulatory and corporate community

• This is impossible without genuine collaboration between ALL stakeholders

• We believe the IMF is uniquely poised to address this issue and bring many of these key stakeholders together…

M-Power = Myeloma Power

The core vision of this initiative is to improve the short- and long-term outcomes of African American patients with myeloma.

We want to empower patients and communities to change the course of myeloma…

Increase awareness and reduce stigma

Engage the community

Shorten the time to diagnosis by educating primary care providers

Enhance access to care

Educate providers about culturally sensitive care

The Rationale

• We are very aware of disparities in MANY groups!

• These include race, ethnicity, geography, insurance status, age, gender, and others…

• The disparity in the African American community is the highest in MM and likely the highest in ALL cancers – so we are directing our initial efforts in this community

• Analogy of the house on fire…

• We are already planning other efforts in the Hispanic/Latinx community

Faith Community Nurses

Meeting Communities Where They Are

Levine Cancer

Center & Atrium

A “Surround” Strategy Black Health Matters

Educational Materials

University of MD

M-Power Website & Toolkit

Videos & Podcasts Cancer Center Customize d Education

Print Materials Community Organizations

Emory / Grady

Council

The current or FUTURE patient, family member, or caregiver

Churche s

MSK

Moffit

Involved Support Group Leaders

Michigan State/ Karmanos

Thousands of print publications distributed

165+ US Support Groups Free Community Workshops

Meet the Team

Robin Tuohy

Yelak Biru

Michelle Faber Selma Plascencia

Rafi Stephan

Haleigh Wolfe

Nancy Bruno

Meghan O'Connor

Kelly Cox

Joseph Mikhael

Diane Moran

Peter Anton

M-Power Website and Video Reach

…with fresh content, resources added regularly & a page for each city

Meeting Patients and Communities Where They Are Through Engaging, Creative Formats

Healthy Churches 2030 Conference with Doug E Fresh

Customizable Education Options presented to community leaders (e.g. faith nurses, habitat for humanity, divine 9)

Myeloma as the 5th Cancer in community cancer education

Myeloma Added to Family Cancer Education Program

470 Physical Posters + e- version

Myeloma Made Simple in 5 minutes

Cancer Resource Bags delivered directly to neighborhoods

Post-ASH Facebook Live

Health Care Provider Education

Course for PCPs

Wraps up this week

Nurse Course

814 live attendees Linked In Live MM for the Primary Care Provider: A Practical Review to Promote Earlier Diagnosis Among Diverse Populations

<- Publications ->

Student Mentor program with NMA launches next week

Medical Student Scholars for Health Equity in Myeloma

Sponsored by the IMF, Cobb Institute and NMA

Disparities in MM Among African Americans

Education of Primary Care Physicians

Our goal is to reduce DELAYS in diagnosis among African Americans by educating the primary care community with a focus on:

• Recognizing the signs and symptoms of myeloma

• Discriminating myeloma from other diagnoses such as diabetes

• Capturing an accurate diagnosis through proper use of testing

• Providing referral guidelines for Hematology and Oncology

• Grand Rounds

• Postcards mailed to 6,000+ PCPs in target cities

• Free PCP CME course “Don’t Miss Myeloma”

• Cobb Institute talk

• Talk at NMA Annual Meeting

• Articles and pending publications

359 Live Attendee s

M-Power Community Workshops

Over 10,000 Enduring Replays

Launched March 20, 2021

129 individuals or households attended

50% Black or African American

98% rated it Excellent or Very Good +++ video replays

June 27,2022

56 individuals or households attended

67% Black or African American

100% rated it Excellent or Very Good

2,112 replays

• 87% reported being more aware of the risks and symptoms of multiple myeloma

• 93% plan to share something learned with a family member, friend, or healthcare provider

Launched Sept 25, 2021

48 individuals or households attended 44% African American

100% rated it Excellent or Very Good 49 requests for mailed materials +++ video replays

• 100% reported being more aware of the risks and symptoms of multiple myeloma

• 92% plan to share something learned with a family member, friend, or healthcare provider

Launched Nov 13, 2021

77 individuals or households attended 52 requests for mailed materials

75% African American

90% rated it Excellent or Very Good ++++ video replays

• 86% reported being more aware of the risks and symptoms of multiple myeloma

• 93% plan to share something learned with a family member, friend, or healthcare provider

Launched Oct 1, 2021

49 individuals or households attended 50 requests for mailed materials

60% African American

90% rated it Excellent or Very Good 1,535 replays in 3 weeks​

• 90% reported being more aware of the risks and symptoms of multiple myeloma

• 95% plan to share something learned with a family member, friend, or healthcare provider​

Medical Student Scholars for Health Equity in Myeloma

Sponsored by the IMF, Cobb Institute and NMA

Medical school students to participate in a health disparities project focused in myeloma alongside an expert in multiple myeloma

GOALS:

• To raise awareness of myeloma in the medical student community and its impact on African Americans

• To support innovative health disparities projects in myeloma and their presentation

• To provide mentorship to medical students with experts in myeloma

• To increase the pool of African American physicians committed to health equity in myeloma.

• To create a community of mentors and mentees from the NMA, the Cobb Institute and myeloma experts that can support each other

Medical Students for Health Equity in Myeloma

• OVER 50 Applications from minority medical students were submitted!

• Selection Committee Selected 12 students (4 from HBCUs)

• Students have been paired with a MM expert to conduct a project in health disparities in myeloma

• Students and mentors will attend the Annual Meeting of NMA in July 2023 where projects will be presented as posters at a special session

• Networking reception will bring together students, mentors, members of SNMA, Cobb Institute and the NMA

• A “community” will therefore be created to further enhance collaboration and career opportunity

Other Collaborative Projects

• Charlotte

• Measurement of burden of disease in African American MM patients prior to and after M-Power

• Capture the number of referrals and percentage of African American patients referred pre/post M-Power

• Old North State Medical Society Chapter of NMA

• Atlanta

• Create an order set in EPIC for suspected MM to include serum protein electrophoresis AND free light chain testing

• Planning a multi-stakeholder roundtable on community engagement

• Black Nurses Association – planning education program for early 2023

• Other scientific studies

• Systematic Review of Health Disparities in MM

• Potential project on measuring time from symptoms to diagnosis over the last several years to capture the potential impact of M-Power in certain cities

• SEER database review of health disparities in MM

"Multiple Myeloma for the Primary Care Provider: A Practical Review to Promote Earlier Diagnosis Among Diverse Populations"

Authors: Joseph Mikhael, Manisha Bhutani, Craig Cole

"Disparities in Multiple Myeloma Among African Americans"

Authors: Joseph Mikhael, Manisha Bhutani, Sagar Lonial

Publications in Progress

1. Culturally Responsive Care Delivery in Oncology: The Example of Multiple Myeloma

Authors – Brandon Blue, Amy Pierre, Joseph Mikhael - under review (submitted Nov 2022)

2. Racial and Ethnic Disparities Influencing Overall Survival in Patients with Multiple Myeloma in the US: A Systematic Literature Review

Authors: Joseph Mikhael, Allie Cichewicz, Elizabeth Mearns, Allicia Girvan, Vicki Pierre, Archibong Yellow-Duke, Frank Cornell, Michael Nixon - being submitted next week!

Publications in Progress contd.

3. Addressing the Disparities: The Approach to the African American Patient with Multiple Myeloma

Authors: Brandon Blue, Manisha Bhutani, Craig Cole, Ashraf Badros, Saad Z. Usmani, Ajay Nooka, Leon Bernal, Joseph Mikhael -

to be submitted shortly

And from the Nurse Leadership Board…

4. Disparities in Clinical Trials

Authors: IMF Nurse Leadership Board Members Rebecca Lu, Donna

Catamero, Kim Noonal, Michaela Hillengass, Joseph Tariman, and Beth

Faiman -

To be submitted shortly

M-Power Website stats

• All Web Visits: Over 250k Page views across main & city sites

Email Stats

• Total Sent: 34 emails

• Total Audience: 218,819

• Open Rate Avg: 28%

“A Day In The Life” Podcast Stats

• Total Listens: Over 4,300

Video Stats:

• Total Views: Over 61k

Health

Disparities is a rapidly moving field…

Facebook Live…

Conclusions

• Health disparities are sadly prevalent across all diseases, but particularly in multiple myeloma

• There are MANY other types of inequity in myeloma, including geography, age, gender, orientation…

• Being aware of these disparities is critical to overcoming them

• The IMF’s M-Power is designed to reduce the inequity with specific emphasis on delayed diagnosis, access to therapy and diversity sensitive clinical care

What Can I Do??

• Be more conscious of the topics of health equity

• Evaluate the opportunities in your experience to reduce disparities

• Support the M -Power movement!

mpower.myeloma.org

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

International Myeloma Foundation

Professor, Translational Genomics Research Institute (TGen)

City of Hope Cancer Center

Director of Myeloma Research and Consultant Hematologist, HonorHealth Research Institute

jmikhael@myeloma.org

M-Power Changing the Course of Myeloma

Multiple Myeloma

Did you know that myeloma is the most common blood cancer in people of African descent? But doctors do not typically check people for myeloma during a regular visit because currently there are no national screening recommendations for myeloma. That’s why it’s important to learn the early symptoms of myeloma and let your doctor know that you or a friend or family member are at added risk for the disease.

Because even though myeloma affects African Americans at greater rates, with early diagnosis and treatment, African Americans can have better overall survival in living with the disease.

How You Can Make a Positive Impact in our Myeloma Community

Ilana Kenville, International Myeloma Foundation

How YOU Can Make A Positive Impact In Our Myeloma Community

Pillars of the IMF

Education Support Advocacy Research

Education

You Are Here

Support

Advocacy

Research

Improving Lives, Finding the Cure: The Fight Against Multiple Myeloma Starts Here

Innovating

Groundbreaking Cure

Today, more than 50 projects are occurring to achieve the basic and translational research that is needed to move closer and closer to a cure .

How YOU Can Make An Impact.

• One-Time

• Monthly

• Major Gifts

• Planned Giving

• Peer to Peer

• Corporate Giving

• Stock/IRA Donation

• Tributes and Memorials

• Partners in Progress

• Vehicle Donation

Peer to Peer Fundraising

Virtual Cooking Class

$5,000 100 % 28

IMF Events

Making An Impact

Brian G.M. Durie, MD

Studio City, CA

Myeloma 101

International Myeloma Foundation

Myeloma 101: What Patients Need to Know

March 18, 2022

Brian G.M. Durie, MD

➢ Long Remissions Common

➢ CURE on the Horizon

Importance of Early Diagnosis

➢ Screening can be a new tool

➢ Start discussions with HR SMM

Potential New Myeloma or Smoldering Myeloma

Any Myeloma Defining Events?

• CRAB,

• >60% PC,

• FLC >100,

• MRI >1 focal

No Myeloma Defining Events (SMM)

High Risk SMM (Median TTP ~2 years)

Intermediate or Low Risk SMM

Treat as Myeloma

Early Therapy with Len or Rd x 2 years

Clinical Trials

Observation

Myeloma Tests Needed

➢ Blood counts: anemia?

➢ Chemistry panel: Creatinine and Calcium

➢ SPEP + IFE and UPEP + UFE

➢ Freelite ratio: involved/uninvolved

➢ S B2M; Albumin; LDH

➢ Bone marrow biopsy: FiSH chromosome testing

➢ Bone imaging: CT [WBLDCT]; MRI; PET

Evolution of Treatment Options 15 Years Ago

First Therapy Relapse

VAD (Chemo)

and Revlimid

Treatment Options in 2023

Median PFS: 47.3 vs 35 mo

Median PFS: 67.5 vs 46.2 mo

Benefit: maintenance until PD!

Active Drugs in MM

What Are The Options?

 Keep Track of Follow-up Tests

Key Points for Ongoing Care

- CBC; SPEP/UPEP; Freelite; SCANS; BM if needed

- FiSH for t[11;14] or high-risk [17P-; 1q+…]

 Alert Doctor to Changes (myeloma/side effects)

 Be Aware of Potential Future Options

 Be Proactive in Seeking Expert Advice

Set Expectations with Your Primary Doctor

IMF Publications

Download Our Publications

The IMF produces and maintains an extensive library of up-to-date educational publications and periodicals for patients and caregivers, as well as for healthcare professionals. All IMF publications are always free of charge and are available to download by clicking the links below.

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

iStopMM: Is Screening the Way to Go?

Sigurður Kristinsson, MD, PhD

Professor of Hematology

University of Iceland

iStopMM

Iceland Screens Treats or Prevents Multiple Myeloma

Professor of Hematology

University of Iceland

Email: sigyngvi@hi.is

Twitter: @sykristinsson

@iStopMM

Sigurður Yngvi Kristinsson, MD, PhD

Screening for monoclonal gammopathy of undetermined significance:

A population-based randomized clinical

PARAPROTEIN = M PROTEIN

• Monoclonal protein in blood or urine – All are identical

• Free light chains (FLC) in blood

– Kappa or lambda

Protein electrophoresis

Monoclonal gammopathy of undetermined significance (MGUS)

• Myeloma precursor

• No underlying lymphoproliferative or plasma cell disease

• Prevalence 4% in 50 years and older

– Prevalence increases with age

• 1-1.5% progress to myeloma or realated disaease annually

• Myeloma is always preceded by MGUS

FLC ratio >100

>1 bone lesion on MRI

>60% plasma cells in bone marrow

Risk of progression to MM

Randomized trials

Given what we know – how should we manage SMM?

*Increasing M-protein or FLC ratio in at least two subsequent evaluations,

**Clinical control, monoclonal protein studies, complete blood count, creatinine, and calcium every 1-3 months,

**Clinical control, monoclonal protein studies, complete blood count, creatinine, and calcium every 4-6 months.

Multiple myeloma

• Malignant disease cause by increase in monoclonal plasma cells in the bone marrow that ususally secrete monoclonal protein (Mprotein)

• Symptoms due to

– Marrow failure

–

Bone disease

–

M-protein

–

Immunodeficiency

–

Kidney disease

–

Plasmacytoma

Survival is really improving

Thorsteinsdottir S et al. Haematologica 2018

Why is survival in myeloma improving?

• High-dose therapy with stem cell support

• Novel drugs

• Improved supportive care

• Prognostic factors

• Earlier treatment?

Does follow-up for MGUS matter?

The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma

Follow-up

of MGUS is important

How do we find asymptomatic people to treat?

By chance?

By screening?

The iStopMM study

Benefits of screening

• Early detection

• Early treatment

• Prevent rather that treat

• Improved survival?

Potential harm of screening

• Cost

• Psychological harm

• Low risk of progression

• Unnecessary evaluations – Bone marrow, X-ray, MRI etc

• Only non-aggressive disease is captured

Overall aims of iStopMM

• Evaluate the impact of screening for MGUS

• Obtain evidence for optimal work-up and follow-up

• Integration biological, imaging, and germline genetic markers in risk models for progression

• Evaluate the impact of screening on quality of life

• Biobanking

• Evaluate the effect of early detection and early treatment

• All Icelanders born 1975 and earlier

How did this work?

• A purple envelope sent to their home address

All 35 laboratories in Iceland participate

Smoldering myeloma

No further work-up

arm

• Followed for progression to multiple myeloma or another malignancy (Cancer Registry)

• Followed for all diagnoses in inpatient and outpatient clinics throughout Iceland (Patient Registry)

• Followed for vital status every 2 months (Population Registry)

• All prescriptions throughout Iceland (Prescription registry)

• Regular quality of life assessments

• November 2016 to October 2018

Recruitment

• 148 708 Icelanders were eligible to participate

• 80 759 (54.3%) agreed to participate

• 75 422 (93.4%) of these participants have since been sampled

Registries

• Patient Registry

–

8,796,659 primary care visits

–

1,239,285 outpatient clinic visits since 2000

– 182,200 hospital admissions since 1990

• Cancer Registry –

11,139 cancers for our participants

• Laboratory Registry – Every laboratory test performed on participants ever

• Prescription Registry

–

17,734,946 prescriptions in the dataset

An important part of the iStopMM study is to evaluate the psychological aspects of screening:

Regular quality of life, anxiety, and well being assessments in all participants

Participation rate

• Email surveys in general have about a 30% response rate

– When more than 12 questions or longer than 5 minutes may fall to 20%

• We sent 13 questionnaires, taking 20-30 minutes to complete

• Audience was motivated to participate initially

– But signed up for a study where they expected to do nothing more

• Based on this we estimated:

– 20-30% initial response

– Increasing to a little more than 30% with two reminders

Tenacious participants

Preliminary results on quality of life assessments

Some results….

• Prevalence of MGUS in Iceland:

–

4.3%

• 3.6% of females

• 5.0% of males

– Increases with age

• 1.4% in age group 40-49 years

• 2.6% in age group 50-59 years

• 4.8% in age group 60-69 years

• 7.9% in age group 70-79 years

• 10.9% in age group 80-89 years

• 14.0% in age group 90-109 years

Prevalence of Smoldering Multiple Myeloma: Results from the iStopMM study

Sigrún Thorsteinsdóttir Íris Pétursdóttir1, Jón K Sigurðsson1, Guðrún Á Sigurðardóttir1, Ásdís R Þórðardóttir1, Brynjar Viðarsson4, Páll T Önundarson4, Bjarni A Agnarsson4, Margrét Sigurðardóttir4, Ingunn Þorsteinsdóttir4, Ísleifur Ólafsson4, Elías Eyþórsson4, Ásbjörn Jónsson4, Petros Kampanis5, Malin Hulcrantz6, Brian GM Durie7, Thorvardur J Löve1, Stephen Harding5, Ola Landgren8, Sigurður Y Kristinsson1,4

1. Faculty of Medicine, University of Iceland, Reykjavík, Iceland

2. Department of Hematology, Rigshospitalet, Copenhagen, Denmark

3. Public Health Sciences, University of Iceland, Reykjavík, Iceland

4. Landspítali University Hospital, Reykjavík Iceland

5. The Binding Site, Birmingham, West Midlands, UK.

6. Memorial Sloan Kettering Cancer Center, New York, NY, USA.

7. Cedar-Sinai Samual Oschin Cancer Center, Los Angeles, CA, USA

8. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA

Monoclonal gammopathy of undetermined significance and COVID-19

A population-based study

Sæmundur Rögnvaldsson1,2#, Elías Eyþórsson2#, Sigrún Þorsteinsdóttir1,3, Brynjar Viðarsson2, Páll Torfi Önundarson1,2, Bjarni A

Agnarsson1,2, Margrét Sigurðardóttir2, Ingunn Þorsteinsdóttir2, Ísleifur Ólafsson1,2, Hrafnhildur L Runólfsdóttir2, Dadi Helgason2, Arna

R Emilsdóttir2, Arnar S Agustsson1,2, Aron H Bjornsson1,2, Guðrún Kristjansdottir2, Ásdís Rósa Þórðardóttir1, Ólafur Skúli Indriðason1,2, Ásbjörn Jónsson4, Gauti Kjartan Gíslason1, Andri Ólafsson1, Hlíf Steingrímsdóttir2, Petros Kampanis5, Malin Hultcrantz6, Brian GM

Durie7, Stephen Harding5, Ola Landgren8, Runólfur Pálsson1,2, Thorvarður Jon Love1,2 , Sigurður Yngvi Kristinsson1,2

1: Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 2: Landspítali–The National University Hospital of Iceland, Reykjavik, Iceland; 3: Rigshospitalet, Copenhagen, Denmark; 4:

Akureyri Hospital, Akureyri, Iceland; 5: The Binding Site ltd., Birmingham, United Kingdom; 6: Memorial Sloan-Kettering Cancer Center, New York City, NY, USA; 7: Cedar-Sinai Samual

Oschin Cancer Center, Los Angeles, CA, USA; 8: Sylvester Cancer Center, University of Miami, Miami, FL, USA

#: Equal contribution (co-first author)

Conclusion

MGUS is not associated with contracting SARS-CoV-2 or increased severity of COVID-19 once infected

Covid-19 vaccinations and the effect on MGUS development

How the M-protein varies by time since vaccination

Contrasts of predictive margins with 95% CIs

The m-protein is constant over time since last vaccinated (keeping age, sex and year constant)

N=28

*FLC ratio >100 or M-protein >30 g/L

MGUS

• Arm 1

– Traditional health care

• Arms 2 and 3

–

Medical history and clinicial examination

– Blood work-up in all individuals

• Arm 3

–

Extensive blood work, bone-marrow, low-dose CT in all patients

– Annual follow-up

– More intense bone marrow evaluations

Conclusions

• In this large prospective population-based screening study, the iStopMM study, including >75,000 screened persons, we have identified 3,725 individuals with monoclonal gammopathy

• In the RCT, after 3 years of follow-up, we show that active screening identifies significantly higher number of individuals with full-blown malignancy and smoldering disease

• Our findings illustrate the fact that early detection and intervention is achievable

Population-based nationwide clinical trial with early intervention

Early intervention

• Early intervention offered to individuals with SMM –

KRd in high risk SMM –

Rd in intermediate risk SMM

• Balance of treating only those that need treatment

• So far no SMM patient has progressed to MM

• Following changes in incidence of MM

So, should we screen for MGUS?

• Although our findings are encouraging, until final results of the iStopMM study become available, including data on survival and quality of life, we advise against systematic MGUS screening in healthy individuals

The iStopMM team

Frontline Therapy Peter Voorhees, MD Levine Cancer Institute

Multiple Myeloma: Frontline Therapy

Peter Voorhees, M.D. Clinical Professor of Medicine

Chief, Plasma Cell Disorders Division

Department of Hematologic Oncology and Blood Disorders

Levine Cancer Institute, Atrium Health / Wake Forest School of Medicine

Outline

• The drugs we use to treat newly diagnosed myeloma

• How we choose best therapy for our patients with myeloma

• The evolving role of transplant in frontline therapy

• Treatment of patients who cannot or do not want an upfront transplant

• Treatment of patients who can and want an upfront transplant

• Maintenance therapy

• Conclusions

The Myeloma Treatment Paradigm

Transplant candidate

Induction therapy

Consolidation therapy

Maintenance therapy

Non-transplant candidate

Induction therapy

Maintenance therapy

The Drugs

The Core Pillars of Myeloma Therapy

• The Immunomodulatory Drugs (IMiDs)

• Thalidomide, Lenalidomide (Revlimid), Pomalidomide (Pomalyst)

• The Proteasome inhibitors

• Bortezomib (Velcade), Carfilzomib (Kyprolis), Ixazomib (Ninlaro)

• The CD38 antibodies

• Daratumumab (Darzalex), Isatuximab (Sarclissa)

• Alkylating Agents

• Cyclophosphamide (Cytoxan), Melphalan (Transplant)

• Steroids

• Dexamethasone, prednisone

How to Choose

Factors to Consider in Treatment Choice

• Patient preference

• Shared decision-making model

• Transplant or No Transplant

• Other medical conditions

• Neuropathy, heart disease, kidney disease

• Standard or high-risk myeloma

• Logistical factors

• Distance from the infusion center

Treatment Attrition in Multiple Myeloma

• Real-world assessment of lines of therapy and outcomes based on 3 US insurance claims databases

Put your best foot forward

The Evolving Role of Transplant in Myeloma

Autologous Stem Cell Transplant / Rescue

Transplant Outcomes by Age

• Retrospective CIBMTR analysis

• 15,999 patients

• 2092 ≥70 years old

OS for Pts Treated with MEL200

Transplant Outcomes by Kidney Function

• Retrospective CIBMTR analysis

• 1492 patients

• Normal kidney function: 1240 pts

• Moderately impaired kidney function: 185 pts

• Severely impaired kidney function: 67 pts

• Transplant-related mortality 0% in pts with moderate to severe renal impairment

• Kidney function not associated with inferior progression-free or overall survival

DETERMINATION: Phase III Study of Upfront vs Deferred

Transplant in Newly-Diagnosed Multiple Myeloma

• 3 cycles of RVd induction  ASCT  2 cycles of RVd consolidation  len maintenance vs 8 cycles of RVd induction  len maintenance

Progression-Free Survival

Median PFS: 46.2 vs 67.5 months (HR 1.53, 95% CI

1.23 – 1.91, P < 0.001)

Overall Survival

5-Year OS: 79.2% vs 80.7% (HR 1.1, 95% CI 0.73 – 1.65, P >0.99)

RVd = Revlimid, velcade and dexamethasone

DETERMINATION: Quality of Life

(Baseline N >300 patients per arm)

DETERMINATION: Outcomes by High-Risk Cytogenetics

Shaded areas indicate 95% CIs

Treatment: Transplant Ineligible or Deferred

Lenalidomide (Revlimid) and Dexamethasone: The Backbone for

Newly-Diagnosed, Patients with Transplant-Ineligible Multiple Myeloma

Rd = Revlimid and dexamethasone; MPT = melphalan, thalidomide and dexamethasone

SWOG S0777: Adding Bortezomib (Velcade) to Revlimid and Dexamethasone

Randomized, phase III trial comparing bortezomib, lenalidomide and dexamethasone to lenalidomide and dexamethasone for patients with newly diagnosed myeloma not eligible for or declining upfront transplant

Median OS: 69 months vs Not Reached (>84 months, HR 0.709, 95% CI 0.543 – 0.926)

Median PFS: 29 vs 41 months (HR 0.742, 95% CI 0.594 – 0.928)

• 43% ≥65 years old, 57% <65 years old

• ≥Grade 3 Neurologic AEs: 33%

Rd = Revlimid and dexamethasone; VRd = Velcade, Revlimid and dexamethasone

Durie, B, et al. Lancet 2017;389:519-27.

Durie, B, et al. Blood Cancer J 2020;10:53.

RVD-Lite

Induction: Nine 5-Week Cycles •

Consolidation: Six 4-week cycles

•

15; Bort D1, 15

• Median Age 73 (65 –93) • ≥Grade 3 PN: 2%

35.1 mos

MAIA: Adding Daratumumab (Darzalex) to Revlimid and Dexamethasone

Multicenter, randomized (1:1), open-label, phase 3 study

DRd (n = 368)

Key Eligibility Criteria

• NDMM

• Transplant ineligible

• CrCl ≥30 mL / min

Stratification factors

• ISS stage

• Age < 75 vs ≥75

• Geographic location

28-day cycle

Daratumumab 16 mg/kg IV

• Days 1, 8, 15 and 22 in Cycles 1-2, days 1 and 15 Cycles 3-6, day 1 Cycle 7+ until PD

R 25 mg PO

• Days 1-21 of each cycle until PD

D 40 mg PO weekly until PD

Rd (n = 369)

28-day cycle

R 25 mg PO

• Days 1-21 of each cycle until PD

D 40 mg PO weekly until PD

Primary endpoint

• PFS

Secondary endpoints

• TTP

• ORR

• sCR/CR

• MRD

• OS

• PFS2

• Safety

MAIA: Demographic and Baseline Disease Characteristics

D-Rd, daratumumab/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; ISS, International Staging System; MM, multiple myeloma. a2 patients had an ECOG PS score >2 (1 patient each with an ECOG PS score of 3 and 4). bIncludes IgD, IgE, IgM, and biclonal.

•

MAIA: Updated Efficacy Results

Phase III Study of Lenalidomide and

Facon, T, et al. Lancet Oncol 2021;22:1582-96.

Facon, T, et al. NEJM 2019;380:2104-15.

Progression-Free Survival

Treatment: Transplant Eligible

Dexamethasone for Transplant-Eligible Patients with Newly Diagnosed Myeloma

Randomized, phase III trial comparing bortezomib, thalidomide and dexamethasone to thalidomide and dexamethasone as induction therapy before and consolidation therapy after tandem autologous stem cell transplantation

CASSIOPEIA: Adding Darzalex to Velcade, Thalidomide and Dexamethasone for Patients Undergoing Upfront Transplant

Induction Four 28-day Cycles

Consolidation Two 28-day Cycles

Darzalex + Velcade, Thalidomide and Dexamethasone

Velcade, Thalidomide and Dexamethasone

Darzalex + Velcade, Thalidomide and Dexamethasone

Velcade, Thalidomide and Dexamethasone

every 8 weeks for up to 2 yrs

CASSIOPEIA: Progression-Free and Overall Survival

0.58 (95% CI 0.47–0.72)

Median follow-up: 44.5 months

PFS: not reached

HR 0.54 (95% CI 0.37–0.79) D-VTd: 41 deaths VTd: 73 deaths

Velcade and Dexamethasone for Patients with Newly Diagnosed Myeloma

Undergoing Upfront Transplant

Induction Four 21-day Cycles

Consolidation Two 21-day Cycles

Maintenance

Darzalex + Velcade, Revlimid and Dexamethasone

Darzalex + Velcade, Revlimid and Dexamethasone

Velcade, Revlimid and Dexamethasone

Velcade, Revlimid and Dexamethasone

GRIFFIN: Baseline Disease Characteristics

ITT, intent-to-treat; ISS, International Staging System; MM, multiple myeloma. aECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.

bThe ISS disease stage is based on the combination of serum β2-microglobulin and albumin levels. Higher stages indicate more advanced disease. cCytogenetic risk was assessed by fluorescence in situ hybridization (locally tested) among patients with available cytogenetic risk data; high risk was defined as the presence of del(17p), t(4;14), or t(14;16). Laubach, J

GRIFFIN: Longitudinal Outcomes

Patient Reported Outcomes: Quality of Life in GRIFFIN

Quality of life improvements seen in multiple domains for both groups but numerically favoring Dara-RVd, including global health score, physical functioning, EQ-5D-5L visual analog scale, EQ-

5D-5L utility score, disease symptoms, and future perspective

Maintenance Therapy

Thank you to our Sponsors!

Approaches to Relapse Panel Discussion

led by Brian G.M. Durie, MD

International Myeloma Foundation

The Approach to Relapse Panel Discussion

Saturday, March 18, 2023—Boca Raton, FL

Beth Faiman, PhD, MSN, APN-BC, AOCN®, BMCTN®, FAAN, FAPO

IMF Nurse Leadership Board

Cleveland Clinic

Taussig Cancer Institute

Cleveland, OH

Nikhil Munshi, MD

Harvard Medical School

Dana-Farber Cancer Institute

Boston, MA

Peter Voorhees, MD

Atrium Health

Levine Cancer Institute

Charlotte, NC

Therapy Options for RRMM Patients

First Relapse

Risk Stratification of Active MM

Myeloma Treatment Paradigm

Active Drugs in MM

What Are The Options?

MM: Second or Higher Relapse

Therapeutic advances have led to prolonged survival in MM, but it remains a chronic disease

Newer drugs increase the options available

Treatment of myeloma requires a long-term strategy

Key is delivering the best “package” of treatment at a given stage

Optimal combinations and sequencing are key

Risk-stratified approach in clinic

Future will be developing more individualized approaches

Immune Therapies Nikhil Munshi, MD

Dana-Farber Cancer Institute

Immunotherapy of multiple myeloma

Nikhil C. Munshi, MD

Professor of Medicine

Harvard Medical School

Kraft Family Chair

Director, Basic and Correlative Science

Jerome Lipper Multiple Myeloma Center

Dana-Farber Cancer Institute

Boston VA Healthcare System

Disclosures

Advisory Board/Consultant: Adaptive, AbbVie, Amgen, BMS, Celgene, DCT, Janssen, Karyopharm, Legend, Novartis, Oncopep, Takeda

Scientific Founder: Oncopep, DCT

Immune-therapies under investigation in Hematological Malignancies

Immunotherapy1,2

Active (Designed to act on the immune system itself)

I-O therapies

Therapeutic cancer vaccines

• Immune effector cell modulators

• Checkpoint Inhibitors

• Co-stimulatory agonists

Unspecific

• Cell-based

• DC-based cancer vaccines

• Single antigen/ peptide-based

• Cytokines

• Interleukins

• Interferons

• IMiDs

Passive (Designed to act on the tumor)

Antitumor mAbs Adoptive

• Tumordirected mAbs

• Ab-drug Conjugates (ADC)

• Cell therapies

• Adoptive T-cell therapy

DC, dendritic cell; IMiD, immunomodulatory agent; I-O, immuno-oncology; mAb, monoclonal antibody. 1. Finn OJ. Ann Oncol. 2012;23(suppl 8 ):viii6-viii9.

Mellman I et al. Nature. 2011;480:480-489.

What Immune-based Therapies Are Available

• Immunomodulatory agents – Thalidomide, Lenalidomide and Pomalidomide – iberdomide, CC92480

• Antibodies – Daratumumab, Elotuzumab, Isatuximab

• Checkpoint inhibitors

• Antibody drug conjugates - Belantemab

• CAR-T cell therapies – Ide-cel, Cilta-cel. Anti-GPRC5D

• BiTES – anti-BCMA, Anti-GPRC5D, anti-FCRL-5 •

Chimeric Antigen Receptor

T cells (CAR T Cells)

• Exploit native antibody or T cell recognition and signaling pathways

• Introduction of unique genes through viral vectors to allow recognition of tumor cells

• Targeting – A unique tumor specific antigen

• Effective tumor cell killing

• Dramatic expansion after infusion

Image courtesy of Stephan Grupp, UPenn

Tumor-specific BCMA CAR construct

T cell

Native TCR

Tumor cell

BCMA

CAR-T cell

Dead tumor cell

CAR T Production

Promising MM antigens for current targeted immunotherapies

BCMA SLAMF7 1 3 6

CD38

Phase 2 KarMMa Study: Ide-cel in Relapsed Refractory Multiple Myeloma

Ide-cel efficacy: longer follow-up (median 24.8 months)

Patients treated at 450 × 106 cells target dose had an ORR of 81% and a CR/sCR of 39%

• Median time to first response of 1.0 month (range 0.5−8.8); median time to CR

(range 1.0−15.8)

• Median follow-up of 24.8 months (range 1.7−33.6) across target dose levels

• Of those patients with a complete response or better, 79% were MRD negative

KarMMa: Robust PFS and OS Outcomes With Ide-Cel

PFS: Overall and According to Target Dose1

OS by Number of Prior Lines of Therapy and in All Ide-Cel–Treated Patients2

• PFS increased by depth of response; median PFS was 20 months in patients with CR/sCR

• ASH 2022: patients achieving early and sustained undetectable MRD after ide-cel had prolonged PFS3 (Oral abstract Monday, December 12, 2022, 3:30 PM)

Ciltacabtagene Autoleucel in RRMM (CARTITUDE)1

Binding Domains

Cilta-cel structure: two

BCMA-targeting domains

designed to confer avidity plus a 4-1BB costimulatory domain

CARTITUDE-1: tested cilta-cel in patients with PS ≤1 and receiving ≥3 prior therapies, including a PI, an IMiD, and an anti-CD38 therapy, or doublerefractory to PIs and IMiDs

JNJ-4528

LCAR-B38M

JNJ-68284528

Ciltacabtagene autoleucel

VHH VHH

 Median time to first response: 1 month (0.9–8.5)

 Responses ongoing in 70 (72.2%) patients

 Of evaluable patients, 93.0% achieved MRD 10-5 negativity

Median time to MRD 10-5 negativity: 1 month (0.8–7.7)

 Among patients with 6 months individual follow-up, most had cilta-cel CAR+ T cells below the level of quantification (2 cells/µL) in peripheral blood

CAR, chimeric antigen receptor; CR, complete response; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. PR or better, Independent Review Committee assessed. No patient had CR or stable disease as best response. cMRD was assessed in evaluable samples at 10-5 threshold by next-generation sequencing (clonoSEQ, Adaptive Biotechnologies) in all treated patients at Day 28, and at 6, 12, 18, and 24 months regardless of the status of disease measured in blood or urine; patients were not evaluable primarily due to lack of an identifiable clone in the baseline bone marrow sample. dAll treated patients.

Cilta-cel Achieves Long Duration of Response in RRMM

Cilta-cel is associated with sustained MRD negativity and better long-term outcomes for a broad range of patients with specific characteristics

27-month PFS 54.9% (95% CI, 44.0-64.6)

Median PFS Not reached (95% CI, 24.5–NE)

27-Month OS 70.4% (95% CI, 60.1–78.6)

Median OS Not reached (95% CI, 27.2 months–NE)

27-mo PFS – MRD- >12 months 78.8% (95% CI, 51.5 – 91.8)

27-Mo OS – MRD- >12 months 90.8% (95% CI, 67.7-97.6)

ASCO 2022 UPDATE

ASCO 2022 UPDATE

KarMMa subgroup analysis: Ide-cel yielded high response rates in most subgroups, including high-risk patients

• ORR was ≥65% and CR rate was ≥20% across all high-risk subgroups except R-ISS disease stage III

• Presence of extramedullary disease and baseline tumor burden did not substantially affect ORR

Data cutoff date: 14 Jan 2020.

CR, complete response; ORR, overall response rate; PR, partial response; R-ISS, revised International Staging System; sCR, stringent complete response; VGPR, very good partial response. aSum of CR/sCR, VGPR, and PR rates may differ from the ORR rate due to rounding. Raje N, et al. Presented at 62nd ASH Meeting 2020. Abstract 3234.

• Median time to first response was 1.0 month in both elderly groups and in the overall treated populationb

• Median duration of response was consistent across age groups, ranging from 10.7 to 11.0 months b

• Ide-cel yielded high response rates in most subgroups, including high-risk patients2

• ORR was ≥65% and CR rate was ≥20% across all high-risk subgroups except R-ISS disease stage III2

Ide-cel is currently approved by the FDA. The safety and efficacy of ide-cel is still under investigation by other regulatory authorities. Data cut-off date: 14 January 2020. aValues may not add up to total due to rounding; bTime to first response and duration of response were assessed in responders: n = 38 for ≥ 65 years group, n = 18 for ≥ 70 years group, and n = 94 for overall ide-cel treated population. cCRS graded according to Lee criteria (Lee DW, et al., Blood 2014;124:188-195); dInvestigator-identified NT events were graded according to the NCI CTCAE v4.03. 1. Berdeja J, et al. Presented at ASH 2020; abstract 1367. 2. Raje N, et al. Presented at ASH 2020; abstract 3234.

The overall response and safety profile for the elderly groups were comparable with those observed in the overall population1

Efficacy and Safety of Cilta-cel in Lenalidomide-Refractory Patients with Progressive Multiple Myeloma after 1–3 Prior Lines of Therapy: CARTITUDE-2

CARTITUDE-2: Cilta-Cel Appears Active in High-Risk RRMM

Cohort B of the phase 2 CARTITUDE-2 study assessed cilta-cel in patients with MM who had early relapse (≤12 months after ASCT or ≤12 months after start of initial treatment with antiMM therapy)1

ORR: 100% (19/19)

• High response rate in this challenging population

• 90% remained progression-free at 1 year post cilta-cel infusion

• Results at 18 months of follow-up show durability and deepening of response, maintenance of PFS

≥CR value does not sum appropriately due to rounding.

Toxicity Profile

• Cytokine Release Syndrome – CRS

• Neurotoxicity

• Cytopenia

• Infections and Hypogammaglobulinemia

• Other Toxicities

Cytokine Release Syndrome (CRS)

CAR-T related neurotoxicity, aka ICANS: Immune effector

cell-associated neurotoxicity syndrome

• (Headache)

• Lethargy

• Agitation

• Tremor • Aphasia

• Delirium

• Encephalopathy

• Seizures

• Cerebral edema

• Usually after CRS

Difficulty concentrating

 CAR T cells  Fever  Hospitalization  Dexamethasone  Fludarabine

CRS and ICANs With BCMA CAR-T Constructs1

What Are the Emerging other CAR T Studies in MM?

Construct Current Status

Comments

CT-053

Phase 2

Humanized CAR T cells

P-BCMA-01

Phase 2

Autologous T stem cell

memory (Tscm) CAR-T cells; also an Allo program

CRB-402

Phase 2

BB21217 – Memory CAR T cells

ALLO-715

Phase ½

Allogeneic CAR T cell

CT-103A

Phase 1

Fully humanized CAR T cells

Overview of the CAR T cell administration process1,2

Ex vivo CAR T cell manufacturing Collection Infusion

Grow and expand number of T cells

Identify patients eligible for CAR T cell therapy

Evaluation and selection of the patient in the CAR T cell therapy center

Apheresis and transport of cells to CAR T cell manufacturing site

Isolate and activate T cells

Engineer T cells with CAR gene

Bridging therapy (post-apheresis, and typically stopped 2 weeks prior to infusion)2

Lymphodepletion therapy

(3 consecutive injections 3–5 days before CAR T cell infusiona)3,4

Infusion and monitoring (infusion to Day 28)3

Monitoring medium-term (Day 28–100)3 and long-term (> Day 100)3 complications

Image extracted from: Dana-Farber Cancer Institute, How CAR T cell therapy works. Available from: https://www.dana-farber.org/cellular-therapies-program/car-t-cell-therapy/how-car-t-cell-therapy-works/. Accessed February 2020. Flowchart extracted from: Moran D. The potential of CAR T-cell therapy and the myeloma patient journey. Myeloma Today. Available from: https://indd.adobe.com/view/07583bc3-3af4-4a8d-a142-47cb2c8a6402. Accessed February 2021. aTypically fludarabine/cyclophosphamide.

CAR, chimeric antigen receptor.

1. Moran D. The potential of CAR T-cell therapy and the myeloma patient journey. Myeloma Today. Available from: https://indd.adobe.com/view/07583bc3-3af4-4a8d-a142-47cb2c8a6402. Accessed February 2021.

2. Protocol for: Raje N. N Engl J Med 2019;380:1726-37. 3. Yakoub-Agha I, et al. Haematologica 2020;105:297–316. 4. Turtle CJ, et al. Sci Transl Med. 2016;8:355ra116.

Which patient to Consider?

Identifying patients eligible for CAR T cell therapy

Patient eligibility should be determined prior to leukapheresis

Which patient to Consider? Identifying patients eligible for CAR T cell therapy

Treatment characteristics: Disease characteristics: Patient characteristics:

Patients who have received at least four prior MM treatment regimens:a,1,2

• Including a PI, an IMiD® agent and an anti-CD38 mAb

Patients who have progressive disease:1,2

• Do not need to be refractory to the last treatment regimen; stable disease or minimal response are acceptable

• Do not need traditional measurable disease; imaging is adequate

No age limit for eligibility to receive CAR T cell therapy:1,3

• If patients are over 75 then they will be judged on an individual basis

Patients must be willing and able to adhere to the clinic visit schedule and other requirements:1,4

• Patients must agree to continued follow-up for gene therapy trials (as mandated by the regulatory guidelines)

aReflecting inclusion criteria in pivotal clinical trials – approved indication may vary. CAR, chimeric antigen receptor; IMiD® agent, immunomodulatory drug; mAb, monoclonal antibodies; MM, multiple myeloma; PI, proteasome inhibitor. 1. Personal opinion of speaker based on expert panel manuscript pending publication. 2. Shah N, et al. J Immunother Cancer. 2020;8:e000734. 3. Berdeja J, et al. Presented at ASH 2020; abstract 1367. 4. Protocol for: Raje N. N Engl J Med 2019;380:1726-37.

Comorbidities and relevant considerations

Cardiorespiratory

Well managed and compensated cardiorespiratory comorbidities are acceptable.1,2 No fixed EF requirement which are liberal than those required for high-dose therapy and transplant.

Renal function

Patients with adequate renal function defined as CrCl ≥ 30 mL/min using Cockcroft-Gault equation, will be included1–3

Decreased renal function would require dose reduction for fludarabine and cyclophosphamide during lymphodepletion1–3

Viral

CAR T cell therapy should be deferred for patients with active ongoing viral infection, e.g. HCV, HBV or HIV.1,2

Immune status

Patients considered for CAR T cell therapy irrespective of recurrent, non-severe infections1,2

CAR, chimeric antigen receptor; CrCl, creatine clearance.

Factors impacting CAR T cell therapy outcomes and the risk of toxicities

Patient on chronic immunosuppressantsa should be considered with a possibility to hold it during CAR T cell therapy.1,2

Ongoing treatment with intermittent topical, inhaled or intranasal corticosteroids is allowed

Patients on anticoagulation should have no active bleeding and should be safe to be taken off anticoagulation1,2

Adequate bone marrow function is not a prerequisite for consideration for CAR T cell therapy1,3

• There are minimal blood count requirements for a patient to be considered for therapy1,2

• A low count (ANC < 1000 cells/mm3 and/or platelet count < 50,000 mm3) may impact production of adequate CAR T cells, and may also increase risk of more prolonged cytopenia following lymphodepletion1,2

Cilta-cel is not approved by any regulatory agency. Ide-cel is currently approved by the FDA only. AE, adverse event; ANC, absolute neutrophil count; CAR, chimeric antigen receptor. 1. Personal opinion of speaker based on expert panel manuscript pending publication. 2. Protocol for: Raje N. N Engl J Med 2019;380:1726-37. 3. Shah N, et al. J Immunother Cancer. 2020;8:e000734. 4. Munshi NC, et al. Presented at ASCO 2020; abstract 8503. 5. Madduri D, et al. Presented at ASH 2020; abstract 177.

CAR T cell therapy differs from ASCT

• It is important to consider patient eligibility and treatment characteristics when deciding between CAR T cell therapy and ASCT:1

CAR T cell treatment ASCT

Patient characteristics

Patients ≥ 70 years2,3

Cardiorespiratory or renal comorbidities2–4

At risk of infection4,5

Treatment characteristics

Need for induction2,3

Need for T/PBS cell collection2,5

Short recovery time4–6

ASCT, allogeneic hematopoietic stem cell transplantation; CAR, chimeric antigen receptor. 1. Personal opinion/experience of the speaker. 2. Protocol for: Raje N. N Engl J Med 2019;380:1726-37. 3. Al Hamed R, et al. Blood Cancer J. 2019;9:44. 4. Shah N, et al. J Immunother Cancer. 2020;8:e000734. 5. Multiple Myeloma Research Foundation. The difference between cellular therapy and autologous stem cell transplant. Available from: https://themmrf.org/2020/02/24/the-difference-between-cellular-therapy-and-autologous-stem-celltransplant/#:~:text=The%20interaction%20between%20the%20engineered,a%20lot%20of%20interest%20recently.&text=In%20ASCT%2C%20the%20cells%20are,not%20modified%20in%20any%20way. Accessed February 2020. 6. Martin T, et al. Presented at ASH 2020; abstract 2291.

What is Bispecific Antibody?

Cell Death

T cell activation

Cytokine secretion

Cytotoxicity

Bispecific Antibody Constructs Facilitate Cell-to-Cell Interactions via Dual Antigen Specificity

Redirects CD3+ T cells to BCMA + MM cells

Induces T cell-mediated killing of MM patient cells

BCMA Teclistamab CD3

Teclistamab: An Off-the-Shelf, T-Cell–Redirecting Bispecific Antibody1

• Binds to CD3 on T cells and BCMA on plasma cells

• Mediates T-cell activation and subsequent lysis of BCMA-expressing MM cells

• Teclistamab was tested in the MajesTEC-1 study

– RP2D for teclistamab monotherapy: 1.5 mg/kg SC QW with step-up doses of 0.06 and 0.3 mg/kg

MajesTEC-1: Teclistamab Is Highly Active in Triple-Class–Refractory MM1,2

Screening Treatment

Cohort A

Triple-class exposed

Key eligibility criteria

• Documented, measurable RRMM

• ≥3 prior lines, including prior PI, IMiD, and anti-CD38 therapy

• No prior BCMA-targeted therapy

• Primary endpoint: ORR

Week 1

• Step-up doses of teclistamab SC (0.06 and 0.3 mg/kg)

Cycles ≥1

• Weekly teclistamab SC 1.5 mg/kg

• Continue until PD

• ORR of 63% in patients with triple-class–exposed disease

• Median DOR of 18.4 months

• MRD negativity rate: 24.7% (10-5)

– 26.7% in the all-treated (N = 165) patient population

–

81.5% of MRD-evaluable patients (44 of 54) were MRD negative

– Almost half (46.2%) of patients with ≥ CR were MRD negative

MajesTEC-1: Robust PFS and OS Outcomes in RRMM1

Median: 11.3 mo (95% CI, 8.8-17.1)

Median: 18.3 (95% CI, 15.1-NE)

ASH 2022: Baseline correlatives for pivotal RP2D patients support clinical combinations of teclistamab with agents such as daratumumab or checkpoint inhibitors. Updated oral abstract Saturday, December 10, 9:30 AM2

Practical Points: The Safety Experience With Teclistamab1

Maximum CRS Grade

• All CRS events were grade 1/2, except for 1 transient grade 3 CRS event that occurred in the context of concurrent pneumonia (resolved in 2 days)

• All CRS events fully resolved without treatment discontinuation or dose reduction

• 5 patients (3.0%) had a total of 9 ICANS events (7 events were concurrent with CRS)

• All ICANS events were grade 1/2 and fully resolved

• No treatment discontinuations or dose reductions due to neurotoxic events, including ICANS

MagnetisMM-1: Elranatamab Is Active in RRMM1

• Elranatamab: a humanized BsAb targeting BCMA and CD3

• Preclinical studies have demonstrated antitumor activity and delayed tumor progression

• Elranatamab was given SC at doses from 80 to 1,000 mcg/kg either weekly or every 2 weeks

• Confirmed OR was 64% among 55 patients receiving elranatamab at a dose >215 mcg/kg and 35% (19 of 55) of patients achieved ≥ CR

1. Jakubowiak AJ et al. ASCO 2022. Abstract 8014.

New Directions: Targeting GPRC5D and CD3Talquetamab Is Active in RRMM

Both RP2Ds of talquetamab have comparable safety, efficacy, and pharmacokinetic profiles

New Directions: Targeting FcRH5 and CD3 Cevostimab is Active in RRMM

Cevostamab is a humanized IgG1-based T-cell–engaging BsAb that targets FcRH5 on myeloma cells and CD3 on T cells

• Dual binding induces T-cell activation and potent T-cell–directed killing of myeloma cells

Phase 1 dose-escalation and dose-expansion study evaluating the safety and efficacy of Q3W IV cevostamab in patients with RRMM1

• Cevostamab was given as a fixed-duration treatment for up to 17 cycles (≈1 year)

• Cycle 1 step-up dosing was evaluated to mitigate CRS

ASH 2022: enduring responses after 1-year, FD cevostamab therapy in patients with RRMM; early experience from a phase 1 study2 (Oral abstract Saturday, December 10, 5:30 PM)

Plans to Improve the Outcome of CAR-T Cell Therapy

Improve the CAR T cell product

• Improve response and overcome resistance:

– Dual antigen binding1

– RNA CARs2

– Peptide stimulated T cells with vaccine3

– Find novel targets ( e.g. GPRC5D4)

• Improve expansion and reduce risk of toxicities:

– Suicide genes/safety switches as a means to deactivate CAR T cells2

– Gene editing (e.g. PD-1 knockdown2)

– Select CD4:CD8 ratios2

– PI3K inhibitors5

• Reduce turnaround time:

– Gene editing of allogeneic CAR T cells2,6

Increase target expression

• Gamma-secretase inhibitors for BCMA7

Improve the CAR T cell treatment protocol

• Optimize infusion schedule:

– Retreatment at progression8

• Improve patient selection:

– Treat at an earlier line of therapy9

– Treat patients with a low disease burden9

– Treat patients regardless of high-risk disease9

• Use rational combinations OR maintenance therapy:

– Checkpoint inhibitors1, IMiDs10

1. Wang Z, et al. J Hematol Oncol. 2017;10;53. 2. Rafiq S, et al. Nat Rev Clin Oncol. 2020;17;147–67. 3. Ma L, et al. Immunotherapy. 2019;365;162–168. 4. Smith EL, et al. Science Translational Medicine. 2019; 11:eaau7746. 5. Petersen CT, et al. Blood Adv. 2018;2;210 –23. 6. Graham C, et al. Cells. 2018;7;155. 7. Roex G, et al. Pharmaceutics. 2020;12;194. 8. Maude SL, et al. Blood. 2017;130;2238–40. 9. Raje N, et al. Presented at 62nd ASH Meeting 2020; abstract 3234. 10. Wudhikarn K, et al. Hematology (Am Soc Hematol Educ Program). 2020; 1:272–9.

Conclusions

• Immune and biologic therapies are achieving an unprecedented level of responses in late stages of myeloma

• Tumor intrinsic and microenvironmental factors both at diagnosis and at relapse, have significant role in outcome

• Task to develop therapies that sustains the deep response – to lead to cure !

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