2025 Seattle RCW Slides

SEATTLE, WA

AUGUST 9, 2025

Thank you to our sponsors!

Welcome & Introductions

Robin Tuohy

Vice President, Patient Support

International Myeloma Foundation

Understanding Myeloma Basics

Anupama Kumar, MD

University of California San Francisco, CA

IMF REGIONAL COMMUNITY WORKSHOP

SEATTLE MORNING AGENDA

(Video) Closing the Gap: Health Disparities in Myeloma

Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, Chief Medical Officer, International Myeloma Foundation

Advancing Treatment Options Through Clinical Trials

Andrew Cowan, MD

Fred Hutchinson Cancer Center, Seattle, WA

Q&A with Panel

Coffee Break

Breakout: Frontline or Relapsed Treatment Approaches

-NDMM: Getting Started with Myeloma Management

Anupama Kumar, MD

-RRMM: Continuing the Myeloma Treatment Journey

Andrew Cowan, MD

Housekeeping Items

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

Program Evaluations: evaluations at the end of today.

Restrooms: Bathrooms are located upstairs on the Mezzanine level, and a code is required.

Men: 4550

Check in with IMF staff at welcome desk for the code as needed.

Parking: If you have parked at the hotel today, please check in with an IMF team member at the registration desk, our team will provide a voucher to provide to the valet team.

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

We greatly appreciate your time and feedback!

Scientific Advisory Board

S. Vincent Rajkumar, MD IMF Board Chair

Thomas Martin, MD

UCSF, Helen Diller Family Comprehensive Cancer Center

Wee Joo Chng, MD

National University of Singapore

María-Victoria Mateos, MD, PhD   University of Salamanca

Vania Hungria, MD, PhD Santa Casa de São Paulo

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

Sigurður Yngvi Kristinsson, MD, PhD University of Iceland

Philippe Moreau, MD University Hospital of Nantes

Shaji Kumar, MD Mayo Clinic

NIkhil Munshi, MD Dana-Farber Cancer Institute

Jesús San Miguel, MD, PhD   University of Navarra

Sagar Lonial, MD, FACP

Winship Cancer Institute, Emory University

Saad Zafar Usmani, MD, MBA, FACP, FASCO

Memorial Sloan Kettering Cancer Center

The IMF Support Group Team is Here

For You!

Shared Experiences Help to Better Understand the Myeloma Journey

• Support Groups empower patients & care partners with information, insight & hope

• The IMF provides educational support to a network of over 150 myeloma specific groups

150+ US Support Groups

Over 200 Support Group Visits/year

 Northwest MM Fighters!

 Meets mostly virtually on the 4th Saturday of each month at 10:00AM Pacific Time

 Northwest MM Fighters Care Partners Support Group

 Meets virtually on the 1st Saturday of each month at 10:00AM Mountain Time

Special Interest Groups

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

 MM Families

 Founded in 2021

 For patients & care partners with young children

 Las Voces de Mieloma

 Founded in 2022

 For Spanish speaking patients & care partners

 Living Solo & Strong

 Founded in 2022

 For patients without a care partner

Click here for more inf

 Smolder Bolder

 Founded in 2023

 For smoldering myeloma patients & care partners

 Veterans SIG

 Founded in 2025

 For those who served our country

 High Risk Multiple Myeloma

 Founded in 2023

 For high-risk myeloma patients & care partners

 Care Partners Only

 Founded in 2024

 For myeloma care partners only

CLINICAL TRIALS MATCHING ENGINE

Seamlessly matching patients to the latest clinical trials.

• Discover clinical trials tailored to your myeloma journey with the IMF.

• Filter by diagnosis, treatment, and location to find the best fit for you.

Clinical Trials Matching Engine Usage

WRITTEN EDUCATION

Live Patient Education

2025 Live Patient Education

Patient & Family Seminars

• Boca Raton, FL – March 14 – 15

• Philadelphia, PA – May 2 – 3

• Los Angeles, CA – August 15 – 16

• Chicago, IL – October 3 – 4

Myeloma Community Workshops

• Virtual - March 4

• San Mateo, CA - March 29

• Atlanta, GA - April 5

• Edina, MN - April 26

• Denver, CO - June 21

• Virtual – July 29

• Seattle, WA - August 9

• Waltham, MA - September 27

• Raleigh-Durham, NC - November 15

• Virtual – November 18

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

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

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

The IMF Grassroots Advocacy Program is multi-faceted and growing

• Advocacy Training & Leadership Development

• Policy and Legislative Education

• Grassroots Campaign Planning

• Health Policy Forums & Roundtables

• Advocacy Resource Development

• Storytelling and Personal Narratives

Scan for Upcoming Programs and Events!

Understanding Myeloma Basics

Anupama Kumar, MD

University of California San Francisco, CA

Understanding Myeloma Basics

Anupama Kumar, MD

August 9, 2025

What is multiple myeloma?

How did I develop myeloma?

• You didn’t do anything wrong!

• Error in DNA of plasma cell leads to abnormal plasma cell

• Abnormal plasma cells can multiply until they reach a “critical threshold” and cause symptoms

• Generally NOT carried in families

Risk factors

• Age – median age is late 60s

• Usually there is no identifiable exposure

• Obesity

• Race/ethnicity

• 1 in 5 patients with myeloma are African American

• Higher incidence in Hispanic patients

Disparities

Myeloma begins as MGUS

MGUS has a 1% risk of progression per year

Smoldering myeloma has a 10% risk of progression per year

Initial symptoms of myeloma

• Fatigue

• Weight loss

• Bone pain, fractures

• Cord compression – numbness, weakness

• Kidney failure – decreased urination, bubbly/frothy urine

• “Incidental” diagnosis – workup by hematologist, primary care, nephrologist, endocrinologist, neurologist

Myeloma workup

• Blood tests

• Complete blood count

• Comprehensive metabolic panel

• SPEP

• Immunofixation

• Free light chains (kappa, lambda)

• Immunoglobulins (IgG, IgA, IgM)

• Beta 2 microglobulin, LDH, albumin

Myeloma workup

• Blood tests

• Complete blood count

• Comprehensive metabolic panel

• SPEP

• Immunofixation

• Free light chains (kappa, lambda)

• Immunoglobulins (IgG, IgA, IgM)

• Beta 2 microglobulin, LDH, albumin

Myeloma workup

• Blood tests

• Complete blood count

• Comprehensive metabolic panel

• SPEP

• Immunofixation

• Free light chains (kappa, lambda)

• Immunoglobulins (IgG, IgA, IgM)

• Beta 2 microglobulin, LDH, albumin

Myeloma workup

• Blood tests

• Complete blood count

• Comprehensive metabolic panel

• SPEP

• Immunofixation

• Free light chains (kappa, lambda)

• Immunoglobulins (IgG, IgA, IgM)

• Beta 2 microglobulin, LDH, albumin

Myeloma workup

• Blood tests

• Complete blood count

• Comprehensive metabolic panel

• SPEP

• Immunofixation

• Free light chains (kappa, lambda)

• Immunoglobulins (IgG, IgA, IgM)

• Beta 2 microglobulin, LDH, albumin

Myeloma workup

• Blood tests

• Complete blood count

• Comprehensive metabolic panel

• SPEP

• Immunofixation

• Free light chains (kappa, lambda)

• Immunoglobulins (IgG, IgA, IgM)

• Beta 2 microglobulin, LDH, albumin

IFE False Positives

• SPEP/M-spike = 0.2

• IFE = IgG kappa

• This patient has IgD lambda MM

• How did this happen?

IFE False Positives

• SPEP/M-spike = 0.2

• IFE = IgG kappa

• This patient has IgD lambda MM

• The patient is on daratumumab

IFE False Positives

• Monoclonal antibodies (daratumumab/isatuximab) can cause a small M-spike, corresponding to IgG kappa

• Special tests, using mass spectrometry, can differentiate

Myeloma workup

• Urine tests – “random” or 24 hour

• Total protein

• UPEP

• UIFE

• Bone marrow biopsy

• Imaging

• X-rays

• CT skeletal survey

• PET/CT scan

• MRI

Myeloma workup

• Urine tests – “random” or 24 hour

• Total protein

• UPEP

• UIFE

• Bone marrow biopsy

• Imaging

• X-rays

• CT skeletal survey

• PET/CT scan

• MRI

Myeloma workup

• Urine tests

• Spot or 24 hr protein, UPEP, UIFE

• Bone marrow biopsy

• Imaging

• X-rays

• CT skeletal survey

• PET/CT scan

• MRI

Bone marrow biopsy

Morphology

Karyotype FISH

Van De Donk et al. (2023), https://doi.org/10.1038/sj.leu.2402768

Bone marrow biopsy: MRD testing

• MRD = minimal residual disease.

• MRD negative = no residual myeloma

• 2 methods:

• NGS (ClonoSEQ) – precise to 10-6, need original “ID” specimen

• Flow cytometry – precise to 10-5

Myeloma workup

• Urine tests

• Spot or 24 hr protein, UPEP, UIFE

• Bone marrow biopsy

• Imaging

• X-rays

• CT skeletal survey

• PET/CT scan

• MRI

Imaging

PET/CT scan with diffuse (“salt and pepper”) involvement throughout bone marrow (A, B) and focal lesions at L humerus (C, D) and L sacrum (E, F)

BEFORE treatment AFTER treatment

Rubini et al. (2014), https://doi.org/10.1016/j.critrevonc.2016.03.006

The myeloma spectrum

MGUS Smoldering myeloma Early Active Myeloma Multiple Myeloma

<10% myeloma cells on bone marrow

No SLiM-CRAB features 10-60% myeloma cells on bone marrow No SLiM-CRAB features

Presence of any “SLiM” features:

• ≥60% myeloma cells in bone marrow

• Involved/uninvoled light chain >100

• MRI with >1 lesion ≥5 mm

Presence of any “CRAB” features:

• Ca >11

• Cr>2 or CrCl<40

• Hgb <10

• ≥1 lytic lesion by skeletal survey, CT, or PET

ISS + RISS staging

International Staging System (ISS)

Revised International Staging System (RISS)

Only del 17p, t(4;14) or t(14;16) included in this definition

2025 IMWG Risk Criteria

Intermediate Risk

• Translocation t(4;14), t(4;16), or t(14;20)

• Gain/amp of 1q

• Deletion of 1p32

High-Risk

• deletion 17p (>20%)

• TP53 mutation

• Biallelic deletion of 1p32,

• Beta-2 microglobulin >5.5 plus creatinine <1.2

Other Risk Stratification

• Plasma cell leukemia

• >5% plasma cells in blood

• High disease burden

• Functional high-risk

Myeloma response

• Depth of response

• Partial response: 50% improvement in M-spike

• Very good partial response: 90% improvement in Mspike

• Complete response: M-spike and IFE negative, bone marrow with <5% myeloma cells

• Stringent complete response: CR + light chains normal

• MRD- stringent complete response

Myeloma response

• Response generally deepens over the course of treatment

• The deeper the response, the longer the remission

A primer for looking at clinical trials

• PFS = progression free survival

• How long a patient stays in remission before having to switch to a different treatment

• OS = overall survival

A Kaplan-Meier curve

Why do we treat?

1. To prolong survival

2. To prevent permanent organ damage

3. To reduce symptoms (pain, nerve damage, etc.)

4. To cure patients

Survival is improving

Puertas (2023), http://doi:10.3390/cancers15051558

Emerging treatments

Shah et al. (2021), http://doi:10.3390/cancers15051558

Treatment “phases”

Induction – initial chemotherapy +/- transplant

Consolidation – similar to induction, given after transplant

Maintenance – less intensive phase of treatment

The myeloma toolbox – Chemo + mAbs

Proteosome Inhibitors IMiDs Monoclonal Antibodies Alkylators

Bortezomib (Velcade)

Ixazomib (Ninlaro)

Carfilzomib (Kyprolis)

Lenalidomide (Revlimid)

Pomalidomide (Pomalyst)

Daratumumab (Darzalex)

Isatuximab (Sarclisa)

Elotuzumab (Empliciti)

• Proteosome inhibitors. Proteosomes recycle protein. When proteosomes are inhibited > extra protein builds up > toxic to cell > cell dies

• IMiDs directly kill cancer cells and alter your immune system to better fight cancer

• Monoclonal antibodies target a specific marker, such as CD38 on plasma cells

• Alkylators alter the DNA by adding an alkyl group, inhibiting DNA/RNA replication and leading to cell death.

The myeloma toolbox –transplant

• Melphalan chemotherapy

• Reinfusion of your own stem cells (autologous)

• Typically done after initial “induction” chemotherapy

The myeloma toolbox - immunotherapy

Target BCMA GPRC5D FcRH5

Bispecifics Teclistimab Elaranatamb Talquetamab In trials CAR-T Idecel Ciltacel In trials In trials

Coping with myeloma

• Mental health is important and often overlooked!

• Support

• Friends/family

• Support groups

• Find a mentor

• Understand your medical team

• Doctors - Oncologist, radiation oncology, surgeon, nephrologist

• Nurse, transplant coordinator, MA

• Social work

• Nutrition

• Palliative care

Thank you!

• Patients, caregivers

• UCSF myeloma team – MDs, RNs, BMT coordinators, social work, nutrition, psychology

Closing the Gap: Health Disparities in Myeloma (Video)

Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO Chief Medical Officer, International Myeloma Foundation

Advancing Treatment Options Through Clinical Trials

Clinical Trials

Andrew Cowan, MD

Associate Professor of Medicine

Research Director, Multiple Myeloma

Fred Hutch Cancer Center / UW Medicine

Clinical Trials - Overview

Some Of The Important Principles Of Clinical Trials:

 The drive of research has brought us to where we are

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

 Research is under very tight supervision and standards

 Open, clear communication between the physician and the patient is fundamental Driving research forward!

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

Clinical Trials: Myths

• Phase 1 and 2, everyone gets active treatment

• Phase 3 standard of care vs new regimen: often standard regimen with/without additional agent in MM trials

• Patients can withdraw their consent for clinical trial participation at any time

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

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

MYTH: Clinical trials are expensive and not covered by insurance

• Research costs are typically covered by the sponsoring company

• Standard patient care costs are typically covered by insurance

• Check with clinical trial team/insurers; costs such as transportation, hotel, etc may not be reimbursed and are paid by patient

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

.

Overview of New Drug Development

Identify a target for therapy in the laboratory

Confirm the anticancer activity in laboratory and animal studies

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

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

Preclinical

Clinical Trial Phases

ANIMAL STUDIES: Examine safety and potential for efficacy

PHASE 1

PHASE 2

FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS

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

• Identify AEs

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

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

PHASE 4

INFORMATION COMPARED TO STANDARD OF CARE

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

• Often multiple institutions; single or double blind; sometimes open label

APPROVED AGENTS IN NEW POPULATIONS OR NEW DOSE

Clinical Trials – Why Me??

 Every patient is unique and must be viewed that way

 Benefits of trials are numerous and include:

 Early access to “new” therapy

 Delay use of standard therapy

 Contribution to myeloma world – present and future

 Financial access to certain agents

 Must be balanced with potential risks

 “Toxicity” of side effects

 Possibility of lack of efficacy

Why Do So Few Cancer Patients Participate in Trials?

Patients may:

• Be unaware of clinical trials

• Lack access to trials

• Fear, distrust, or be suspicious of research

• Have practical or personal obstacles

• Face insurance or cost problems

• Be unwilling to go against their physicians’ wishes

• Not have physicians who offer them trials

• Have a disconnect with their healthcare team

Importance of Clinical Trial Participation by Diverse Populations

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

– FDA

Leadership and commitment

Community engagement practices

Investigator hiring, training, and mentoring practices

Patient engagement practices

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

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

Is A Clinical Trial Right For Me?

Discuss with your physician if you are eligible for a clinical trial

Work with your physician to determine the best trial for you

Meet with the clinical research nurse or trials coordinator to discuss the trial

Carefully review the provided “Informed Consent” Describes the study and any potential safety  concerns related to the experimental medication

Commonly Asked Questions

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

Will I need to undergo additional tests?

What is currently known about the new drug or combination?

What benefits can I expect?

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

Can I take my vitamins or other medications?

Can I get the treatment with my local doctor?

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

Clinicaltrials.gov https://clinicaltrials.gov/

ncreasing-diversity-in-cancer-clinical-research

Q&A WITH PANEL

Housekeeping Items

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

Program Evaluations: evaluations at the end of today.

Restrooms: Restrooms are located upstairs across from the elevators.

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

We greatly appreciate your time and feedback!

BREAK

WHEN YOU RETURN FROM BREAK

PLEASE HEAD TO YOUR SELECTED BREAKOUT SESSION:

BREAKOUT A: NDMM - GETTING STARTED WITH MYELOMA

MANAGEMENT

Dr. Anupama Kumar, MD

Please move to Quimby Room

BREAKOUT B: RRMM - CONTINUING THE MYELOMA TREATMENT JOURNEY

Dr. Andrew Cowan, MD

Please remain in this room

Thank you to our speakers & our sponsors!

Newly Diagnosed Myeloma

Anupama Kumar, MD

August 9, 2025

The myeloma toolbox

Proteosome Inhibitors IMiDs Monoclonal Antibodies Alkyalors

Bortezomib (Velcade)

Ixazomib (Ninlaro)

Carfilzomib (Kyprolis)

Lenalidomide (Revlimid)

Pomalidomide (Pomalyst)

Daratumumab (Darzalex)

Isatuximab (Sarclisa)

Elotuzumab (Empliciti)

• Proteosome inhibitors. Proteosomes recycle protein. When proteosomes are inhibited > extra protein builds up > toxic to cell > cell dies

• IMiDs directly kill cancer cells and alter your immune system to better fight cancer

• Monoclonal antibodies target a specific marker, such as CD38 on plasma cells

• Alkylators alter the DNA by adding an alkyl group, inhibiting DNA/RNA replication and leading to cell death.

First step: Induction Transplant Eligible Patients

Many options!

An evolving landscape

• Landscape evolving with more use of quad therapy in MM

Doublets

Triplets

Quads

PERSEUS Trial: DRVd vs RVd

• Compared 4 drug combination to 3 drug combination

• Daratumumab + Revlimid + velcade + dexamethasone (DRVd)

• Revlimid + velcade + dexamethasone (RVd)

• Same drug regimen as the GRIFFIN trial, but in more patients (n=709) and international

• Primary endpoint: progression free survival

• Patient population

• Age 18-70 years

• Transplant eligible

• ECOG 0-2

PERSEUS: Design

Cycle Length = 28 days

D: 1800 mg SC weekly C1-2. Q2 weeks C3-6

V: 1.3 mg/m2 D1, 4, 8, 11

R: 25 mg PO D1 – 21

d: 40 mg PO/IV D1-4, 9-12

CONSOLIDATION

MAINTENANCE

DRVd x 4 cycles

DRVd x 2 cycles

DR > R alone if MRD-

RVd x 4 cycles

RVd x 2 cycles

R until PD or AE

What is different from GRIFFIN?

• Cycle length 28 days (vs. 21 days)

• MRD-guided approach for DR duration (vs. fixed 2 years of dara)

• Dexamethasone pulses

Depth of response

• Those who had DRVd had deeper remission

• MRD rate got better over time

PERSEUS: Efficacy

• After a median of 48 months, those who received DRVd had improved PFS

• It is too early to make any conclusion about survival

ENDURANCE Trial: KRd vs RVd

• Compared two different 3 drug regimens

• Kyprolis + revlimid + dexamethasone (KRd)

• Revlimid + velcade + dexamethasone (RVd)

• High-risk patients not included

• Carfilzomib associated with less neuropathy, but more shortness of breath, high blood pressure, rare heart failure

ENDURANCE Trial: KRd vs RVd

IsKIA: IsaKRd vs KRd

• Compared 4 drug regimen to 3 drug regimen

• Isatuximab + kyprolis + revlimid + dexamethasone (Isa+KRd)

• Kyprolis + revlimid + dexamethasone (KRd)

• Primary endpoint: MRD negativity rate

• Patient Population

• Age 18-70 years

• Transplant eligible

N= 151 N=151

IsKIA: Design

INDUCTION

IsaKRd x 4 cycles

KRd x 4 cycles

Standard Induction/Consolidation, Cycle: 28 days

Isa: 10 mg/kg IV days 1, 8, 15, 22 in C1,  10 mg/kg IV days 1,15 in C2-4

K: 20/56 IV mg/m2 days 1, 8, 15

R: 25 mg PO days 1-21

d: 40 mg PO days 1, 8, 15, 22

CONSOLIDATION

IsaKRd x 4 cycles

Isa-KRd x 12 cycles

IsaKRd x 4 cycles

KRd x 12 cycles

Light consolidation, Cycle: 28 days

Isa: 10 mg/kg IV day 1

K: 56 IV mg/m2 days 1, 15

R: 10 mg PO days 1-21

d: 20 mg PO days 1, 8, 15, 22

IsaKIA: Results

MRD Negativity Post-Consolidation

• Median follow-up: 20 months (short!)

• MRD negativity at 10-6 improved over time

• 27% vs 14% after induction

• 52% vs 27% after transplant

• 67% vs 48% after consolidation

• PFS data not yet available

MASTER trial

• High-risk myeloma accounted for 35% of patients

• DKRd  transplant  DKRd (4-8 cycles)  lenalidomide

• Uses MRD guided approach (BMBx after each phase)

• If MRD- at 2 timepoints  stopped further therapy

• 80% reached MRD- at 10-5

• 71% had 2 MRD and came off treatment

• PFS 87% at 2 years

Choosing an induction regimen

• Should be a personalized decision

• Factors to consider

• Age

• Genetic features of your myeloma

• Overall fitness – Are you transplant candidate?

• Other medical problems

• Side effects

• If pre-existing neuropathy, be careful about velcade

• If pre-existing heart failure, be careful about kyprolis

• Convenience – route of administration (pill vs IV vs shot), # of infusion center visits required

To transplant or not to transplant?

The transplant process

• You don’t need to decide on day 1 of induction!

• We do a full assessment of your organ function to make sure you are healthy enough to get a transplant

• Transplant involves a ~2+ week stay in the hospital

• Transplant side effects – low energy, nausea, vomiting, diarrhea, mucositis, infection, low blood counts

• Need time off work and caregiver support

• 3 month recovery

What’s the data behind transplant?

• Transplant is considered standard of care in patients who are eligible after induction

• The DETERMINATION trial showed a significant PFS benefit

• In high-risk, PFS: 4.5 years in transplant vs 1.5 years in no-transplant

5.5 vs 3.8 yrs remission

Is transplant right for me?

• This should be a personalized decision

• Factors to consider

• Age

• Overall fitness

• Genetic features of your myeloma

• Other medical problems

• Organ function

• Tolerance to induction

• Response to induction

• If unsure, strongly consider banking your stem cells for later use

Can we avoid transplant if MRD-?

• IsaKRd induction x 6 cycles

• If MRD- at -105, randomized 1-to-1:

• Transplant + IsaKRd x 2 cycles

• IsaKRd x 6 cycles

• If MRD+ at -105, randomized 1-to-1:

• Transplant + IsaKRd x 2 cycles

• Tandem transplant)

• In those who were MRD negative after induction, subsequent MRD negative rates after transplant vs additional IsaKRd consolidation were about the same

• We may be able to avoid transplant in MRD negative patients

Maintenance: Which drugs,

and for how long?

Maintenance revlimid

• Maintenance revlimid prolongs survival, many years down the line

Revlimid vs placebo, IFM trial

PFS 3.5 years vs 2 years, HR=0.51

Revlimid vs placebo, CALGB 100104

Patients who got revlimid lived 3 years longer

Doublet maintenance

• May be a preferred strategy in patients who are high-risk and/or MRD+

• Fixed-duration

• GRIFFIN gave revlimid indefinitely, + daratumumab for 2 years

• MRD-adapted

• Currently under investigation (PERSEUS, DRAMMATIC)

“Transplant Ineligible”

Determining transplant eligibility

• Age – avoid if >70-75 yrs?

• Co-morbidities/organ function

• EF ≥40%, DLCOcorrected ≥40%, AST/ALT/ALK ≤3x ULN, TB≤2.0

• Tolerance of induction

• Performance status

How do we optimize care for those who are transplantineligible (TI?)

SWOG 0777

• RVd vs Rd without intent for immediate transplant

Both PFS and OS improved with VRd vs Rd, when adjusting for age

RVd, in pts age ≥ 65 yrs and/or transplant-ineligible

VRd (35d cycles) X 9 Rd (28d cycle) x 6

MAIA: DRd vs Rd

• Intended for older adults (65+) or those with other medical problems

• PFS 5 years (61.9 months) in DRd group

• PFS 3 years (34.4 months) in Rd group

• 32% MRD- in DRd group

• 11% MRD- in Rd group Weisel et al. (2023),

Great outcome!

MAIA

Ph3, DRd vs Rd, in transplant-ineligible (age ≥ 65 yrs and/or co-morbidities)

Botzeomib-sparing regimen with lower rates of neuropathy!

DRd: 28% G1-2 neuropathy, 2% G3 neuropathy

Rd: 18% G1-2-neuropathy, <1% G3 neuropathy

Facon et al, 2020, Lancet Oncology ,

IMROZ

Ph3, IsaVRd vs VRd in transplant-ineligible

Induction

IsaRVd (6wk cycles) X 4 cycles vs

RVd (6wk cycles) x 4 cycles

• Primary endpoint:

• PFS

• Secondary endpoints:

• OS, PFS2, ORR, CR, safety, QOL, MRD

Ongoing Treatment

IsaRd (4wk cycles ) until PD vs Rd (4wk cycles) until PD, then crossover to IsaRd

IMROZ

Ph3, IsaVRd vs VRd in transplant-ineligible

IMROZ

Ph3, IsaVRd vs VRd in transplant-ineligible

Estimated OS @ 60 months: 77.3% with IsaVRd vs 66.3% with VRd

BENEFIT

Ph3, IsaVRd vs IsaRd in transplant-ineligible

IsaVRd (28d cycles) X 12 vs.

IsaRd (28d cycles) x 12

IsaVR (28d cycles) X 6 vs. IsaR (28d cycles) x 6

Primary endpoint: - MRD (at 10-5) @ 18 months

Secondary endpoints: - CR rate, MRD- CR rate, VGPR+ rate, PFS, OS, safety

until PD

BENEFIT

Ph3, IsaVRd vs IsaRd in transplant-ineligible

At median of 23.5 months f/u, PFS and OS data still immature

Managing Side Effects

Common Side Effects

• Daratumumab/isatuximab – infusion reaction, decreased ability to make antibodies (infection)

• Lenalidomide – rash, diarrhea, cramping, low blood counts, blood clots, teratogenic, secondary cancer

• Bortezomib – neuropathy, GI toxicities, styes

• Carfilzomib – fever, shortness of breath, nausea, high blood pressure, heart failure

Less dex?

• Long-term dex associated with side effects, especially in elderly

• French trial compared revlimid + dexamethasone (Rd) to daratumumab + revlimid (DR)

• DR group had better response (ORR 89% vs 77%), quicker response (5 months vs 11 months to get to VGPR), and more MRD negativity (33% vs 18%)

Manier et al. (2022),

Adjunct Therapies

Adjunct Therapies

• Bone strengtheners

• Zoledronic acid

• Denosumab

• Calcium/vitamin D

• Infection prevention

• Acyclovir/valacyclovir – prevent VZV infections

• Trimethoprim sulfamethoxazole, atovaquone, dapsone – prevent certain types of pneumonia (PJP)

• IVIG – if IgG <400 + frequent infections

• Blood clot prevention

• Aspirin

• Apixaban, rivaroxaban, etc

Future directions?

Thank you!

• Patients, caregivers

• UCSF myeloma team – MDs, RNs, BMT coordinators, social work, nutrition, psychology

Breakout B

RRMM: Continuing the Myeloma Treatment Journey

Relapsed Therapy

Andrew Cowan, MD

Associate Professor of Medicine

Research Director, Multiple Myeloma

Fred Hutch Cancer Center / UW Medicine

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

OBJECTIVES

 Review the important trend of using an aggressive approach in early treatment of myeloma

 Outline the key results from recent trials in early relapse

 Discuss the approach to late relapse and the use of novel therapies such as CAR T and bispecific antibodies

An Approach to Relapsed MM

• It is not a simple algorithm of treatment #1 then 2 then 3…

• Leverage the benefit of multiple mechanisms of action in combination therapy

Categories:

• 1-3 prior lines

• Later Relapse

• Refractory to PI, IMiD and MoAb = Triple Class Refractory

Definitions:

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

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

• Refractory: progression despite ongoing therapy

• Progression: change in M protein/light chain values

• Line of therapy: change in treatment due to either progression of disease or unmanageable side effects

• Note: initial (or induction) therapy + stem cell transplant + consolidation/ maintenance therapy = 1 line of

Therapy Selection Considerations

Disease-Related

• Nature of the relapse

– Biochemical vs symptomatic

• Risk stratification

– High-risk chromosomal abnormalities: del(17p), t(4;14), t(14;16)

• Disease burden

Therapy-Related

• Previous therapies

• Prior treatmentrelated adverse event

• Regimen-related toxicity

• Depth and duration of previous response

• Cost to patient

Patient-Related

• Renal insufficiency

• Hepatic impairment

• Comorbidities

• Preferences

• Social factors

– Support system

– Accessibility to treatment center

– Insurance coverage

Multiple Myeloma is Not One Disease!

RVD+ASCT+Lenalidomide Maintenance

Relapse 2

Relapse 1

Time: Years! D i s e a s e A c t i v i t y

Relapse 1

Relapse 2

Relapse 3

Relapse 1

1. Therapies change over time— clinical trials make this possible 2. Outcomes (e.g. survival) changes over time, as new therapies emerge

GENERAL PRINCIPLES

3. If one therapy did not work well, it doesn’t mean another won’t

4. Terms like “overall survival” and “progression free survival” typically refer to statistical probabilities for GROUPS of people and do not seal the fate of an INDIVIDUAL

5. At a given point in time, there may not be a known “right answer;” hence many opinions

Pillars of Myeloma therapy

Emerging immunotherapies in multiple myeloma

Modified from: Shah A, Mailankody S. BMJ 2020; 370

Naked antibodies

Examples:

Cancer cell

Antibody drug conjugate

linker

Examples:

1. Belantamab mafodotin (Blenrep) — recognizes BCMA

IS BLENREP (BELANTAMAB) COMING

BACK?

DREAMM 7: Velcade-Dex with

Belantamab or daratumumab

Progression free Survival Overall Survival

Hungria V. NEJM; 391(5): 393-407.

DREAMM 8: POM-DEX WITH BELANTAMAB

OR VELCADE

Progression free Survival

Dimopoulos MA. NEJM 2024; 391(5): 408-421.

Overall Survival

BISPECIFIC ANTIBODY

Bispecific MM target Brand name

Teclistamab BCMA Tecvayli

Talquetamab GPRC5D Talvey

Elranatamab BCMA Elrexfio

Cevostamab FcRH5

Livoseltamab BCMA

Bispecific antibody

Plasma cell aka myeloma cell T-cell • Cytokine release • T cell activation • Perforin/Granzymes

Fc domain

CAR-T CELLS

Early Relapse

General Principles

Use mechanisms of action not previously used

Do not continue to use lenalidomide if progressing on len maintenance

Triplets are preferred over doublets

In real practice - most patients receiving VRD (Bortezomib-LenalidomideDex) like regimens, 1st relapse is typically

Daratumumab + Pomalidomide + Dex (APOLLO)

Isatuximab + Pomalidomide + Dex (ICARIA)

Daratumumab + Carfilzomib + Dex (CANDOR)

Isatuximab + Carfilzomib + Dex. (IKEMA)

Selinexor + Bortezomib + Dex (BOSTON)

Important Update – CAR T cell therapies can be used as early as first relapse!

First or Second Relapse (Options after Considering Clinical (Modified from mSMART But Added New CAR-T Approvals)

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

Refractory to Lenalidomide

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

Not Refractory to Anti-CD38 Refractory to Anti-CD38 and Len DPd or IsaPd Or DVd

Favor CAR-T Cilta-cel (1+ prior LOT) Or Ide-cel (2+ prior LOT)

Others to the left if not candidate for CAR-T

Standard Risk and >23 years remission <2 years of remission and/or HRCA > 2-3 year remission and standard risk < 2 year remission or HRCA Cilta-cel CAR T or Anti-CD38 + Kd

Dingli D, et al. Mayo Clin Proc. 2017;92(4):578-59. Updated 2024.

Abecma (CAR T) vs Standard of Care: 2-4 prior lines of therapy

Carvykti (CAR T) vs Standard of Care: 1-3 prior lines of therapy

OVERALL RESPONSE RATE AND PFS OF RECENTLY APPROVED THERAPIES IN RRMM

Richardson Blood 2014; 123:1826-32

Siegel Blood 2012; 120:2817-25

Lonial Lancet 2016; 387:1551-60

Rasche EHA 2024, P915

Van de Donk ASCO 2023; abs 8011

Lesohkin Nat Med 2023; 29:2259-67

Munshi NEJM 2021; 384:705-16

Munshi EHA 2023; S202

Huang ASCO 2024; 7511

CAR T-Cell Therapy Patient Journey

Immune cells from the patient are collected

Standard of care therapy is permitted until CAR T cells are ready for infusion

Fludarabine and Cytoxan are used to create “immunologic space” to CAR T cells to expand

CAR T: Expected Toxicities

Cytokine release syndrome Neurotoxicity (ICANS)

Cytopenias Infections

CRS ICANS

Onset 1 9 days after CAR Tcell infusion 2 9 days after CAR Tcell infusion

Duration 511 days 317 days

Symptom

s

Managem

ent

• Fever

• Difficulty breathing

• Dizziness

• Nausea

• Headache

• Rapid heartbeat

• Low blood pressure

• Actemra (tocilizumab)

• Corticosteroids

• Supportive care

• Headache

• Confusion

• Language disturbance

• Seizures

• Delirium

• Cerebral edema

• Antiseizure medications

• Corticosteroids

*Based on the ASTCT consensus; †Based on vasopressor; ‡For adults and children >12 years; §For children ≤12 years; ‖Only when concurrent with CRS

Bispecific and Trispecific Antibodies

There are currently 3 approved bispecific antibodies:

Teclistamab (Tecvayli)

Talquetamab (Talvey)

Elranatamab (Elrexfio)

Bispecific Antibodies

Bispecific antibodies are also referred to as dual specific antibodies, bifunctional antibodies, or T-cell engaging antibodies

Bispecific antibodies can target two cell surface molecules at the same time (one on the myeloma cell and one on a T cell)

Many different bispecific antibodies are in clinical development; none are approved for use in myeloma

Availability is off-the-shelf, allowing for immediate treatment

Cohen A et al. Clin Cancer Res. 2020;26:1541.

BCMA, GPRC5D, or FcRH5

Examples:

• Elranatamab

• Teclistamab

• TNB-303B (ABBV-383)

• REGN5458

• Cevostamab

• Talquetamab

Bispecific

Antibodies: Expected Toxicities

• Cytokine release syndrome (CRS)

• Neurotoxicity (ICANS)

• Usually occurs within first 1–2 weeks

• Frequency (all grade and grade 3–5) higher with CAR T

• Cytopenias

• Target unique

• For example, rash, taste disturbance seen with GPRC5D, but not with BCMA

• Infections

• Incidence for bispecifics at RP2D not yet known

• Viruses: CMV, EBV

• PCP/PJP

• Ongoing discussions regarding prophylactic measures

 IVIG

 Anti-infectives

Similarities and Differences Between CAR T-Cell

Therapy and Bispecific Antibodies

Approved product Abecma, Carvykti Tecvayli

Key Points – CAR T and Bispecifics

CAR T and bispecific antibodies are very active even in heavily pretreated patients.

Side effects of CAR T cells and bispecific antibodies include cytokine release syndrome, confusion, and low blood counts, all of which are treatable.

Abecma and Carvykti are only the first-generation CAR T cells and target the same protein. Different CAR Ts and different targets are on the way.

Bispecific antibodies represent an “off-the-shelf” immunotherapy; Tecvayli was approved in October 2022, and now Talvey and Elrexfio in August 2023

Several additional bispecific antibodies are under clinical evaluation.

Emerging Therapies for

Relapsed/Refractory Multiple Myeloma

Bispecific antibodies

• Cevostamab, Alnuctamab, ABBV383, and others

• Target BCMA, GPRC5D, or FcRH5 on myeloma cells and CD3 on T cells

• Redirects T cells to myeloma cells

Cereblon E3 ligase modulators (CELMoDs)

• Iberdomide

• Targets cereblon

• Enhances tumoricidal and immune-stimulatory effects compared with immunomodulatory agents

Small molecule inhibitors

• Venetoclax

• Targets Bcl-2

• Induces multiple myeloma cell apoptosis

The Evolution of Myeloma Therapy

VD

Rev/Dex

CyBorD

VTD

VRD

KRD

D-VMP

DRD

ASCT

Tandem ASCT (?)

Nothing

Thalidomide?

Bortezomib

Ixazomib

Lenalidomide

Combinations

Bortezomib

Lenalidomide

Carfilzomib

Pomalidomide

Selinexor

Panobinostat

Daratumumab

Ixazomib

Elotuzumab

Isatuximab

Belantamab mafodotin*

Melphalan flufenamide*

Idecabtagene autoleucel

Ciltacabtagene autoleucel

Teclistamab, Talquetamab

Elranatamab

D-VRD

Isa-VRD

D-KRD

Isa-VRD “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; PD-L1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib.

Speaker’s own opinions.

CAR T Cell Therapy

Bispecific/Tri-specific

Antibodies

Venetoclax

PD/PDL-1?

Small Molecules

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

Anito-cel

Cevostomab

Linvoseltamab

Iberdomide, Mezigdomide

Sonrotoclax

LUNCH

Please remain in this room

Walk Through the IMF Website

Robin Tuohy

Vice President, Support Groups, International Myeloma

Foundation

IMF REGIONAL COMMUNITY WORKSHOP

SEATTLE

AFTERNOON AGENDA

Seasons of Myeloma: Managing Side Effects and Living Well

Daniel Verina, DNP, RN, ACNP-BC

Mount Sinai Hospital, New York City, NY

Living the Myeloma Life: Local Patient & Care Partner

Flora Ostrow (Patient) and Betsy Gilbert (Care Partner)

Beyond Myeloma Therapy: Palliative Care for the Life

You Are Still Living

Richa Thakur, MD

Fred Hutchinson Cancer Center, Seattle, WA

Q&A with Panel

Closing Remarks

Robin Tuohy

Vice President, Support Groups, International Myeloma

Foundation

Coffee/Network

Walk Through the IMF Website

Robin Tuohy, Vice President, Support Groups

International Myeloma Foundation

Seasons of Myeloma: Managing Side Effects and Living Well

Daniel Verina, DNP, RN, ACNP-BC

Mount Sinai Hospital, New York City, NY

Seasons of Multiple Myeloma

Daniel Verina, DNP, MSN, RN, ACNP-BC

Mount Sinai Hospital - New York, New York & IMF Nurse Leadership Board member

Wintery Mix of Treatment Options Spring into Managing Side Effects

Summer of Success

Wintery Mix of Treatment Options

Diverse and Complex Treatment Combinations

Myeloma Treatment Common Combinations

Velcade® (bortezomib)

Lenalidomide

DVRd, VRd, Vd

DVRd, VRd, Rd

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

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

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

Ninlaro®(ixazomib) IRd

Empliciti® (elotuzumab) ERd, EPd

Xpovio® (Selinexor) XVd, XPd, XKd

Sarclisa® (Isatuximab) Isa-Kd, Isa-Pd

Blenrep® (Belantamab mafodotin) Bela-d

Abecma® (Idecabtagene Vicleucel) --

Carvykti® (ciltacabtagene autoleucel)

Elrexfio® (elranatamab)

Lynozyfic™ (linvoseltamab)

Tecvayli® (teclistamab) --

Talvey® (talquetamab) --

Venclexta® (venetoclax) Vd + ven

New agents or regimens in clinical trials are possible options

ASCT = autologous stem cell transplant; Bela = belantamab; C = cyclophosphamide; D = daratumumab; d = dexamethasone; E = elotuzumab; Isa = isatuximab; I = ixazomib; K = carfilzomib; M = melphalan; P = pomalidomide; R = lenalidomide; V = bortezomib; ven = venetoclax.

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

Duration: Approximately 2 weeks

Location: Transplant Center

Duration: Approximately 3-4 weeks

Location: Transplant Center

POST-TRANSPLANT

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

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)

Manufacturing takes

≈ 4 to 6 weeks

Bridging therapy may be needed

T-Cell Collection

No driving for 8 weeks

“One

& Done” with continued monitoring

• 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

Bispecific Antibodies

• Different bispecific antibodies have differences in efficacy, side effects

– Available after 4 prior lines of therapy (or clinical trial)

– About 7 in 10 patients respond

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

– CRS and neurotoxicity

– Risk of infection

• BCMA target: greater potential for infection

– Tecvayli® (teclistamab)

– Elrexfio ® (elranatamab)

– Lynozyfic™ (linvoseltamab)

BISPECIFIC ANTIBODIES

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

– Talvey ® (talquetamab)

Spring Into  Managing  Side Effects

The Early Bird Gets the Worm: Communicate

Proactively with Your Healthcare

Team

General Disease and Treatment Side Effects

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

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

Unmanaged Myeloma can cause:

• Calcium elevation

• Renal dysfunction

• Low blood counts

• Infection Risk

• Blood clots

• Bone pain

• Neuropathy

• Fatigue

Side Effects of Treatment can

cause:

• GI symptoms

• Renal dysfunction

• Low blood counts

• Infection Risk

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

How You Feel

• Blood clots

• Neuropathy

• Fatigue

Tip: Keep a Symptom Diary and bring it to appointments

Are Steroids Messing With Your Sunny Disposition?

Steroids enhance the effectiveness of other myeloma therapies

Your provider may adjust your dose. Do not stop or alter your dose of steroids without discussing it with your provider

Steroid Side Effects

• Irritability, mood swings, depression

Managing Steroid Side Effects

• Consistent schedule (AM vs. PM)

• Take with food

• Stomach discomfort: Over-the-counter or prescription medications

• Medications to prevent shingles, thrush, or other infections

• 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

Preventing infections is paramount.

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

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)

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

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

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

Viral: Herpes Simplex (HSV/VZV); CMV

Medication Recommendation(s) for Healthcare Team Consideration

Acyclovir prophylaxis

Bacterial: blood, pneumonia, and urinary tract infection Consider prophylaxis with levofloxacin

PJP (P. jirovecii pneumonia)

Fungal infections

COVID-19 and Influenza

IgG < 400 mg/dL (general infection risk)

ANC < 1000 cells/μL (general infection risk)

Consider prophylaxis with trimethoprim-sulfamethoxazole

Consider prophylaxis with fluconazole

Antiviral therapy if exposed or positive for covid per institution recommendations

IVIg recommended

Consider GCSF 2 or 3 times/wk (or as frequently as needed) to maintain

ANC > 1000 cells/μL and maintain treatment dose intensity

GI Symptoms: Prevention & Management

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

Constipation is more common in the induction phase

• Opioid pain relievers, antidepressants, heart or blood pressure medications (check with provider, pharmacist)

• Supplements: Calcium, Iron, vitamin D (rarely), vitamin B-12 deficiency Increase fiber

• Stay well hydrated

• Fruits, vegetables, high fiber whole grain foods

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

Anorexia, the inability to eat, is common during transplant and resolves with time.

• Hydration is most important

• Small, frequent meals with a focus on protein intake

• You will work closely with a dietician to help monitor your calorie intake

Diarrhea is common during transplant and long-term maintenance therapy. Other medications and supplements

• Hydration is very important

• Electrolyte replacement is common

• Good skin care will help prevent irritation

• Stool exam may be needed to rule-out infection

• If no infection, anti-diarrheal medication may be prescribed

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

Feel Like a Spring Chicken: Prevent and Manage Pain

Pain can significantly compromise quality of life

Sources of pain include bone disease, neuropathy and medical procedures

• Management

– Prevent pain when possible

• Bone strengtheners to decrease fracture risk

• Antiviral to prevent shingles

• Sedation before procedures

– Interventions depend on source of pain

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

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

• Scrambler therapy for neuropathy

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

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 and/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 healthcare 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)

– Poor Nutrition

• Prevention

– Stay hydrated – drink water

– Avoid certain medications when possible (eg, 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

The Early Bird Gets the Worm: Communicate Proactively

with Your Healthcare Team

CAR-T and Bispecific Antibodies: Unique Side Effects

CAR T and Bispecific Antibodies: Unique Side Effects

CRS is a common but often 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 Bispecific Antibodies: Unique Side Effects

Management of Oral Side Effects

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

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

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

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

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

Skin and Nail Side Effects

Possible side effect to some treatments and supportive care medications

Skin Rash:

• Prevent dry skin; apply lotion

• Report changes to your care team

• Medication interruption or alternative, as needed

• Steroids:

– Topical for grades 1-2,

– Systemic and topical for Grade 3

• Antihistamines, as needed

Nail Changes:

• Keep your nails short and clean. 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

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.

Summer of Success

Let the Sun Shine In

Fatigue is the most reported symptom. Sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression 98.8%

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

>35% of patients

≈25% of patients

Bee an Empowered Patient

Ask

questions

– What are my treatment options?

– What are the pros and cons of the different options?

– How will we know if treatment is working?

– What do the different labs mean?

– Who will be monitoring my labs?

– How can I access my test results (eg, patient portal)?

– What will we do if my treatment doesn’t work or quits working?

Participate in decisions

– Share your priorities and preferences

– Include care partner(s) in your discussion

Speak up if something seems different or unusual

– Normally 4 vials of blood but only drawing 3?

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

Live in the sunshine, swim the sea, drink the wild air.

– When is my next appointment?

Communicate with your healthcare team

– Understand the roles of each team member

– Who to contact for your needs (eg, side effects, insurance issues, other)

Develop a support network

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

Care Partners Are Vital for Success

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

• Care partners may help with medical appointments, managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions

• Care partners can be a spouse, close relative, a network of people (family, friends, neighbors, church members, etc)

African Proverb

• 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

Cultivate A Care Network

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

• Multiple studies demonstrate that strong social ties are associated with longevity, improved adherence to medical treatment and overall improved health outcomes

• Care partners can be a spouse, close relative, a network of people (family, friends, neighbors, church members, etc)

• Care partners may help with medical appointments, managing medication, daily living, physical assistance, emotional support, myeloma knowledge, healthy lifestyle, patient advocacy, financial decisions

• Caring for the Care Partner

– Recognize that caregiving is difficult/stressful

– Encourage care partners to maintain their health, interests, and friendships

– The IMF has information and resources to help care partners

Enjoy Life’s Bounty

Harvest Good Health

Have a Primary Care Provider & Have Recommended Health Screenings

• Blood pressure

• Cholesterol

• Cardiovascular disease

• Diabetes

• Colonoscopy

• Women specific: mammography, pap smear

• Men specific: prostate

• Vision

• Hearing

• Dermatologic evaluation

• Dental checkups & cleaning

Develop & maintain healthy behaviors

• Good nutrition

• Regular activity

• Quit tobacco use

• Sufficient Sleep (next slide)

An ounce of prevention is worth a pound of cure. Benjamin

Franklin

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.

Living the Myeloma Life: Local Patient & Care Partner

Beyond Myeloma Therapy: Palliative Care for the Life You

Are Still Living

Richa Thakur,

MD

Fred Hutchinson Cancer Center, Seattle, WA

Beyond Multiple Myeloma:

Palliative Care for the Life You Are Still Living

Richa Thakur, MD

Assistant

Professor in Hematology and Oncology

University of Washington/Fred Hutchinson Cancer Center

Top Five Tips for Patients and Their Loved Ones

1. Palliative care is for any stage in myeloma - don’t wait to ask!

2. You can still get your cancer treatment

3. You stay in control - Palliative care helps you make informed decisions

4. Your symptoms are treatable

5. It supports you AND your whole family

Outline

History and Evolution of Palliative Care

What is Palliative Care?

The Interdisciplinary Team

Why it Matters for Patients with Myeloma

Take the First Step: Advance Care Planning

Outline

History and Evolution of Palliative Care

What is Palliative Care?

The Interdisciplinary Palliative Care Team

Why it Matters for Patients with Myeloma

Take the First Step: Advance Care Planning

History of Palliative Care

Evolution of Palliative Care

Outline

History and Evolution of Palliative Care

What is Palliative Care?

The Interdisciplinary Palliative Care Team

Why it Matters for Patients with Myeloma

Take the First Step: Advance Care Planning

WHO Definition of Palliative Care

Palliative care is a crucial part of integrated, people-centred health services. Relieving serious health-related suffering, be it physical, psychological, social, or spiritual, is a global ethical responsibility. Thus, [regardless of] the cause of suffering … palliative care may be needed and has to be available at all levels of care.

Outline

History and Evolution of Palliative Care

What is Palliative Care?

The Interdisciplinary Team

Why it Matters for Patients with Myeloma

Take the First Step: Advance Care Planning

Interdisciplinary Palliative Care Team

Outline

History and Evolution of Palliative Care

What is Palliative Care?

The Interdisciplinary Palliative Care Team

Why it Matters for Patients with Myeloma

Take the First Step: Advance Care Planning

Challenges You May Face During Treatment

● Multi-drug regimens can possibly increase side effect in some patients

● Limitations of hospice in patients with dialysis and transfusions

● Pain from both disease and treatment

What can palliative care do for you?

Diagnosi

s

Advance Care

Planning

Goals of Care

Psychosocial distress

Goals of Care Family Meetings

Can I still get Palliative Care if….

I want to

- Continue chemotherapy?

- Do not have insurance?

- Want a clinical trial?

- I previously was on hospice and changed my mind?

- I do not live near a palliative care doctor?

Outline

History and Evolution of Palliative Care

What is Palliative Care?

The Interdisciplinary Palliative Care Team

Why it Matters for Patients with Myeloma

Take The First Step: Advance Care Planning

Take the First Step: Advance Care Planning

These are formal ways to outline your wishes and helps guide doctors when you cannot speak for yourself

Benefits of Advance Care Planning:

- Peace of mind for you and your family

- Reduces confusion or conflict during emergencies

- Ensures your care aligns with what Your wishes are

Who is My Decision Maker?

1. Guardian

2. Durable Medical Power of Attorney (not POA for finances)

3. Next of Kin (State Dependent)

a. Spouse or Domestic Partner

b. Adult Children (majority agreement)

c. Parents

d. Adult Siblings

e. Next closest relative…

But, what if I do not trust my decision maker?

Getting Started with Advance Care Planning

Key Documents:

- Health Care Proxy

- Living Will

- Do Not Resuscitate/Do not Intubate Orders (Optional)

How to Get Started:

- Visit TheConversationProject.org

- Look at your state’s website for Advance Directives

- Talk to your doctor

Top 5 Tips for Patients and Their Loved Ones

1. Palliative care is for any stage in myeloma - don’t wait to ask!

2. You can still get your cancer treatment

3. You stay in control - Palliative care helps you make informed decisions

4. Your symptoms are treatable

5. It supports you AND your whole family

Bonus Tip: Advanced Care Planning is about protecting your wishes - not giving up.

Q&A WITH PANEL

Closing Remarks

Robin Tuohy, Vice President, Patient Support International Myeloma

Foundation

Housekeeping Items

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

Program Evaluations: evaluations at the end of today.

Parking: If you have parked at the hotel today, please check in with an IMF team member at the registration desk, our team will provide a voucher to provide to the valet team.

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

We greatly appreciate your time and feedback!

Thank you to our speakers & our sponsors!

OUR VISION:

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

OUR MISSION:

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

IMF Core Values:

These are the core values we bring to accomplishing our mission each day.

Patient Centric

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

Respect All

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

Excellence and Innovation

We value accountability, personal responsibility, and a steadfast commitment to excellence. We respect the legacy and reputation of our organization while seeking new solutions and advancements to improve outcomes, quality of life, and access to the best available resources for everyone impacted by myeloma.

Honor differences

We recognize each team member's skills and talents through collaboration and cooperation. Our programs aim to celebrate and support the diversity of our patients and their communities.