2024 Boca Raton Patient and Family Seminar

March 15 & 16, 2024

THANK YOU TO OUR SPONSORS!

Friday Agenda

• 1:00 – 1:10 PM

Welcome and Agenda Review

• 1:10 – 1:25 PM Hot Topics in Myeloma

• 1:25 – 1:45 PM

Shared Decision Making

• 1:45 – 2:00 PM Myeloma.org: Resource Review

• 2:00 – 2:15 PM Q&A w/ Panel

• 2:15 – 2:45 PM BREAK

• 2:45 – 3:00 PM

• 3:00 – 3:40 PM

• 3:40 – 4:10 PM

• 4:10 – 4:50 PM

• 4:50 – 5:00 PM

• 5:00 – 7:00 PM

Advanced Care Planning

Myeloma 101 & Understanding Your Labs

Financial Considerations in Myeloma

Clinical Trials & Patient/Care Partner Testimonial w/ Q&A

Day 1 Recap, Day 2 Announcements & Evaluations

Welcome Reception & Networking

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

Support.myeloma.org

We are happy to help connect you with an existing support group or help form a new one! We assist with virtual, in-person, and hybrid options for meetings.

Reach out to us at

SGTeam@myeloma.org

Local

Support Groups: You Are Not Alone!

 Miami Multiple Myeloma Support Group

 Meets virtually on the 4th Wednesday of each month at 6:30PM

 Melbourne Multiple Myeloma Support Group

 Meets in-person on the 4th Monday of each month at 10:30AM

Palm Beach County Multiple Myeloma Support Group

 Meets in a hybrid format on the 1st nonholiday Monday of each month at 6:30PM

 Maitland Multiple Myeloma Support Group

 Meets in-person on the 2nd Monday of each month at 6:30pm

 Fort Myers Multiple Myeloma Support Group

 Meets in-person on the 3rd Tuesday of each month at 6pm

 Hollywood Multiple Myeloma Support Group

 Meets virtually on the 1st Tuesday of each month at 6PM

 Jacksonville Multiple Myeloma Support Group

 Meets in a hybrid format on the 2nd Wednesday of each month at 6PM

Local Support Groups: You Are Not Alone!

 Brooksville / Nature Coast Multiple Myeloma Support Group

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

 Tampa CentralMultiple Reasons Support Group

 Meets virtually on the 2nd Thursday of each month at 11AM

 North Tampa Multiple Myeloma Support Group

 Meets in-person on the 3rd Saturday of each month at 10:30AM

 Naples Multiple Myeloma Support Group

 Meets in-person on the 3rd Thursday of each month at 6pm

 Tampa Bay/St Petersburg Multiple Myeloma Educational Group

 Meets virtually on the 1st Saturday of each month at 10:30AM

Local Support Groups: You Are Not Alone!

 Palm Coast Multiple Myeloma Support Group

 Meets in-person on the 2nd Thursday of each month at 3:30PM

Ocala Multiple Myeloma Support Group

 Meets in-person on the 2nd Saturday of each month at 11AM

 Sarasota Multiple Myeloma Network & Education Group

 Meets in-person on the 4th Friday of each month at 11AM

 The Villages Multiple Myeloma Support Group

 Meets in-person on the 1st Tuesday of each month at 1PM

 Panama City Multiple Myeloma Support Group

 Meets in-person on the 2nd Saturday of each month at 10AM

 Tallahassee Multiple Myeloma Support Group

 Meets in-person on the 4th Monday of each month at 5:30PM

IMF – Special Interest Virtual Groups

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

 Las Voces de Mieloma

 Designed for Spanish speaking patients only

 Living Solo & Strong with Myeloma

 Designed for patients without a care partner

Coming Soon!

Care Partners Only

 Designed to address the needs of care partners only

 Smolder Bolder

 Created for people living with Smoldering Multiple Myeloma

 MM Families

 High Risk Multiple Myeloma

 Designed to address the needs of the high-risk MM population

 MGUS 4 Us

 Created for people living with MGUS

 For patients/care partners with young children

EVALUATION

Please be sure to complete your program evaluation today.

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

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

If you are attending Friday program only, we ask that you turn the survey in at the end of the day.

If you are coming back for the Saturday sessions, please hold onto your survey, bring it back tomorrow and turn it in at the end of the program. We greatly appreciate your time and feedback!

Hot Topics in Myeloma

Joseph Mikhael, MD, MEd, FRCPC, FACP

Chief Medical Officer, International Myeloma Foundation

Professor, Translational Genomics Research Institute

City of Hope Cancer Center

Shared Decision

Making:

Be An Active Member Of Your Health Care Team

Teresa Miceli, RN BSN OCN

International Myeloma Foundation - InfoLine Advisor, NLB Member, Support Group Leader (MMSS, Smolder Bolder)

Mayo Clinic – Myeloma Nurse Navigator

National Cancer Institute - Myeloma Patient Advocate

Goals

Review Share Decision Making (SDM)

Identify influencing factors to Treatment Decision Making

Discuss strategies to enhance patient empowerment & promote Shared Decision Making

Individual Beliefs & Preference s

Transplant

Eligible Patients

Individual Care Partner

Family

Initial Therap y

Transplant

Ineligible Patients

A Person With `

Treating Myeloma

Transplant (ASCT) Maintenance

Everyone

Social Network & Obligations

Treatment of Relapsed disease

Consolidation / Maintenance

Continued therapy

Myeloma Symptom s & Treatment Options

Supportive Care

Employme nt & Finances

and tolerability, and quality of life. Blood Cancer J. 2021 Feb 18;11(2):40

` ` `

Quality of Life (QOL) Satisfaction and Adherence

“The aim of shared decision making is to ensure that:

- Patients understand their options and the pros and cons of those options.

- Patient's goals and treatment preferences are used to guide

#6i1 SDM: Patient-Centered

https://www.ahrq.gov/cahps/quality-improvement/improvement-guide/6-strategies-for-improving/communication/strategy6i-shared-decisionmaking.html

Care

Steps in Shared Decision-Making

Recognizing and acknowledging that a decision is needed:

The HCP informs the patient that a decision is to be made and that the patient's opinion is important (Choice talk).

Knowing and understanding the best available evidence-based options:

The HCP explains the options and their pros and cons. The patient expresses their preferences, and the HCP supports the patient in deliberation (Option talk).

The HCP and patient discuss the patient's wish to take part in the decision making and incorporate the patient's values and preferences into the decision (Decision talk).

The

https://www.ahrq.gov/health-literacy/professional-training/shared-decision/index.htm

Stiggelbout

HCP and patient follow-up: Review and evaluate the decision, adjust as needed

AM, Pieterse AH, De Haes JC. Shared decision making: Concepts,

and

Patient Educ Couns.

Oct;98(10):1172-9. doi: 10.1016/j.pec.2015.06.022. Epub 2015 Jul 15.

evidence,

practice.

2015

l HCP=Health Care Provider Choon-Quinones, Mimi, Hose D, Kaló Z, Zelei T, Harousseau JL, Durie B, Keown P, Barnett M, Jakab I. Patient and Caregiver Experience Decision Factors in Treatment Decision Making: Results of a Systematic Literature Review of Multiple Myeloma Decision Aids. Value Health. 2023 Jan;26(1):39-49. doi: 10.1016/j.jval.2022.04.003. Epub 2022 May 22.

Advantages to Partaking in SDM

Patients, regardless of age, want to be a part of treatment

Requires staying informed

Reduces uncertainty and alleviates concerns

Decisions reflect personal and family values

Promotes patient and care partner engagement and sense of empowerment

Positive impact on QOL

Lower demand on health care resources

Terpos, et al.

“The 'efficacy' of treatment means different things to different patients, and treatment decision-making in the context of personalized medicine must be guided by an individual's composite definition of what constitutes the best treatment choice.” Terpos, et al.

2021

https://www.ahrq.gov/cahps/quality-improvement/improvement-guide/6-strategies-for-improving/communication/strategy6i-shared-decisi onmaking.html#6i1

decision-making

Influencing Factors to Treatment Decision-Making

Disease-derived

 Time: Stage, risk stratification, Urgent intervention needed vs time to consider options

 Treatment: Availability/access, effectiveness, toxicity, current research

Patient-derived

Provider-derived  Time limitations

 Support for patient involvement

 Provider bias and preference

 Understanding complex treatment options



Physical and emotional wellness

 Comfort in speaking up “Doctor knows best”



Choon-Quinones, Mimi, Hose D, Kaló Z, Zelei T, Harousseau JL, Durie B, Keown P, Barnett M, Jakab I. Patient and Caregiver Experience Decision Factors in Treatment Decision Making: Results of a Systematic Literature Review of Multiple Myeloma Decision Aids. Value Health. 2023 Jan;26(1):39-49. doi: 10.1016/j.jval.2022.04.003. Epub 2022 May

PMID: 35613958.

Financial, Cultural and Religious factors

 Care partner & social network, transportation

https://www.ahrq.gov/sites/de fault/files/wysiwyg/cahps/qua lity-improvement/improveme nt-guide/6-strategies-for-impr oving/communication/cahps-s trategy-section-6-i.pdf

https://www.valueinhealthjournal.com/action/showFullTableHTML?isHtml=true&tableId=tbl4&pii=S1098-3015%2822%290019

22.

8-X

Patient Empowerment

Stay informed, understand options

 Use reliable and current sources of information

 Use caution considering stories of personal experiences

 Consider your priorities

 Discuss with your care partner

 Consider your goals/values/preferences

 Be a part of the conversation, create a dialog

 Ask questions & Express your goals/values/preferences

 Ask for time to consider options, if needed

 Arrive at a treatment decision together

 Arrange follow up to review and adjust, if needed

HCP

Clinical Experience

Research Results

TREATMENT DECISION

Your Preference

Decision Aids available at Myeloma.org

Moreau. ASH 2015.

Philippe

Knowledge Is Power – Stay Informed Download or order at myeloma.org IMF TV Teleconferences 20 IMF InfoLine 1-800-452-CURE 9am to 4pm PST

Know the Members of Your Care Team

Understand their different roles

Myeloma specialist and General Heme/Onc

Primary care: for health screening, general check ups, vaccinations

Sub-specialists: specialty needs

Keep a contact list of your providers

Primary Care Provider (PCP)

Family/Support Network

Subspecialists

You & Your Care Partner

Allied Health Staff

General Hem/Onc

Myeloma Specialist

Prepare

Prepare For Medical Visits

 Medications: Bring a current list of prescribed and over-thecounter

 Questions: Prioritize questions & concerns including financial issues

 Paperwork needing medical signature (ex FMLA, prior authorizations)

Inform

 Updates: Medical or life changes since your last visit

 Symptoms: How have they changed (improved, worsened, stable)? Keep a symptom diary. Bring it along

 Communicate effectively so your health care team can help

Follow Up

 “Next Steps”: Future appointments, medication changes, treatment plan. Ask for the information in writing or on your patient portal Include a care partner, especially for pivotal appointments

IMF Telemedicine Tip Sheet. In development.

Prepare For Medical Visits

Check with your healthcare team –

 Is telemedicine an option?

 What is the process and what technology is needed?

 Are labs needed in advance? Do you need an order?

Preparation is similar for “in-person” appointment PLUS:

 Location: quiet, well-lit location with strong Wi-Fi is best

 Yourself: Do you need to show a body part - wear accessible clothing

 Vital signs (blood pressure, temp, heart rate, weight) selfserve blood pressure cuff is available at many pharmacies and for purchase

Include a care partner, especially for pivotal appointments

IMF Telemedicine Tip Sheet. In development.

Consider Telemedicine

You & Your Care Partner

Myeloma causes the highest burden of symptoms, most commonly effecting people of older age with other medical issues. Care partner support is valuable in SDM

Care partners assist in many ways

Attending medical appointments, being present to learn and discuss possible treatment options and alert the medical team of side effects to treatment

Some treatment options available only if care partner support exists

Care partners can be one person or a rotation of many people

Building a partnership is based in good communication

Finding the balance:

- helping the patient with needed activities while maintaining a sense of independence

- allowing the care partner to have time for good self-care

Care Partner Tip Card https://www.myeloma.org/resource-library/tip-card-care-partners

Terpos, et al. 2021; Soong, et al., Image Credit: https://www.mmtoldtrue.com/community/care-partner-corner

Resource List

Bylund CL, Eggly S, LeBlanc TW, Kurtin S, Gandee M, Medhekar R, Fu A, Khurana M, Delaney K, Divita A, McNamara M, Baile WF. Survey of patients and physicians on shared decision-making in treatment selection in relapsed/refractory multiple myeloma. Transl Behav Med. 2023 Apr 15;13(4):255-267. doi: 10.1093/tbm/ibac099. PMID: 36688466.

Chari A, Romanus D, DasMahapatra P, Hoole M, Lowe M, Curran C, Campbell S, Bell JA. Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM). Oncologist. 2019 Nov;24(11):1479-1487. doi: 10.1634/theoncologist.2018-0724. Epub 2019 Aug 1. PMID: 31371520; PMCID: PMC6853123.

Choon-Quinones, Mimi, Hose D, Kaló Z, Zelei T, Harousseau JL, Durie B, Keown P, Barnett M, Jakab I. Patient and Caregiver Experience Decision Factors in Treatment Decision Making: Results of a Systematic Literature Review of Multiple Myeloma Decision Aids. Value Health. 2023 Jan;26(1):3949. doi: 10.1016/j.jval.2022.04.003. Epub 2022 May 22. PMID: 35613958.

Rifkin RM, Bell JA, DasMahapatra P, Hoole M, Lowe M, Curran C, Campbell S, Hou P, Romanus D. Treatment Satisfaction and Burden of Illness in Patients with Newly Diagnosed Multiple Myeloma. Pharmacoecon Open. 2020 Sep;4(3):473-483. doi: 10.1007/s41669-019-00184-9. PMID: 31605300; PMCID: PMC7426337.

3718 Cytokine Release Syndrome: The Patient, Caregiver and Healthcare Professional Experience. Janelle Soong, Giuseppe De Carlo, Naziah Lasi-Tejani, Sumanjit K. Sethi, Natacha Bolaños, Martine Elias, Yelak Biru, Solène Clavreul, G. Scott Chandler, Klaus Finzler, Yann Nouet, Antonio Giuseppe Del Santo. Blood (2023) 142 (Supplement 1): 3718

Terpos E, Mikhael J, Hajek R, Chari A, Zweegman S, Lee HC, Mateos MV, Larocca A, Ramasamy K, Kaiser M, Cook G, Weisel KC, Costello CL, Elliott J, Palumbo A, Usmani SZ. Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life. Blood Cancer J. 2021 Feb 18;11(2):40. doi: 10.1038/s41408-021-00432-4. PMID: 33602913; PMCID: PMC7891472.

https://www.ahrq.gov/health-literacy/professional-training/shared-decision/index.html

https://www.ahrq.gov/cahps/quality-improvement/improvement-guide/6-strategies-for-improving/communication/strategy6i-shared-decisionmaking.ht ml#6i1

EVALUATION

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

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

We greatly appreciate your time and feedback!

Myeloma.org

Robin

Tuohy

Vice President, Support Groups

International Myeloma Foundation

EVALUATION

Please be sure to complete your program evaluation today.

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

If you are attending Friday program only, we ask that you turn the survey in at the end of the day.

If you are coming back for the Saturday sessions, please hold onto your survey, bring it back tomorrow and turn it in at the end of the program.

We greatly appreciate your time and feedback!

BREAK

THANK YOU TO OUR SPONSORS!

Myeloma 101 & Understanding Your Labs

Joseph Mikhael, MD, MEd, FRCPC, FACP

Chief Medical Officer, International Myeloma Foundation

Teresa Miceli, RN, BSN, OCN

International Myeloma Foundation Nurse Leadership Board Member

Q&A with Teresa and Dr. Joe: Understanding Myeloma Basics

Joseph Mikhael, MD, MEd, FRCPC, FACP

 Professor, Applied Cancer Research and Drug Discovery, Translational Genomics

Research Institute (TGen), City of Hope Cancer Center

 Chief Medical Officer, International Myeloma Foundation

 Consultant Hematologist and Director, Myeloma Research, Phase 1 Program, HonorHealth Research Institute

 Adjunct Professor, College of Health Solutions, Arizona State University

Teresa S. Miceli RN BSN OCN

Mayo Clinic, Rochester, MN

• Mayo Associate

• Assistant Professor of Nursing

• Myeloma Research RN Navigator

International Myeloma Foundation

• InfoLine Advisor

• Nurse Leadership Board

• Support Group Leader

NCI Myeloma Steering Committee

Myel0ma Statistics

Estimated New Cases in 2023 35,730 %

Median Age At Diagnosis 69 years

How common is Myeloma?

of All

New Cancer Cases 1.8% 5-year Relative Survival 59.8%

dated

Rate of New Cases per 100,000 Persons by Race/Ethnicity & Sex

Percent of New Cases by Age https://seer.cancer.gov/statfacts/html/mulmy.html;

2.15.2024

Bone Marrow Cells – Good & Bad

Platelets

Hematopoietic stem cell Myeloid progenitor cell

Graphic Credit: Teresa Miceli

Lymphoid progenitor cell T cell B cell NK cell Megakaryocyt e Eosinophil Basophil Erythrocytes Monocyte Neutrophil Plasma cell

This Photo by Unknown Author is licensed under CC BY

Dendritic Cell Macrophag e Photo Credit Clonal Plasma cells

(Mono)clonal Plasma Cells

Clonal

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

Heavy Chain = M-Spike

 65% IgG – most common

 20% IgA – associated with AL Amyloid

 5% to 10% light chain-only (kappa, lambda)

 Uncommon: IgD, IgE, IgM

OS, Palsson R., et al. Defining new reference intervals for serum free light chains in individuals with chronic kidney

Normal Ranges vary between labs.

Note the unit of measure (mg/dL vs mg/L): Results adjusted for renal function

eGFR = estimated glomerular filtration rate; M-spike = monoclonal spike; Ig = Immunoglobulin

of the iStopMM study. Blood Cancer J. 2022 Sep 14;12(9):133. doi: 10.1038/s41408-022-00732-3

Long TE, Indridason

disease: Results

K:L ratio eGFR (mL/min/1.73m2) 0.46-2.62 45-59 0.48-3.38 30-44 0.54-3.30 < 30

I m a g e C r e d i t : I M F P a t i e n t H a n d b o o k

Plasma cells

Spectrum of Monoclonal Protein Disorders

Condition

Clonal plasma cells in bone marrow

MGUS1-4 (Monoclonal Gammopathy of Undetermined Significance)

SMM1-5,8 (Smoldering Multiple Myeloma)

• AL-Amyloid

• POEMS

• Light or Heavy Chain Deposition Disease

• MGRS = Renal

• MGNS = Neuro

Active Multiple Myeloma6-8

Presence of Myeloma

Defining Events None None Yes

Likelihood of progression ~1% per year ~10% per year Not Applicable

Treatment No; observation

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

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

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

Yes for high risk*; No for others Yes

* In clinical trial

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

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

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

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

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

<10%

10%-60% >10%

Clonal Bone Marrow

BMPC ≥ 60% S Li

elevation

complications

one

Rajkumar SV, et al. Lancet Oncology. 2014; 15:e538-e548. Kyle RA, et al. Leukemia. 2010; 24(6):1121–1127.

≥ 10%

alcium Bony/Extramedullary Plasmacytoma

enal

nemia

disease

R A B

AND any one or more Myeloma Defining Events (MDE)

Clonal

FLC ratio >100 >1 focal lesion* by MRI

BMPC = Bone marrow plasma cells

CRAB

FLC = serum free light chain * >5 mm Multiple Myeloma and Myeloma Defining Events SLiM

Testing For Myeloma: Blood & Urine

Test Name

CBC + differential

Complete metabolic panel

Beta-2 Microglobulin (B2M)

Lactate Dehydrogenase (LDH)

Serum Immunofixation and Protein

electrophoresis (SPEP+IFE)

Immunoglobulins (G, A, M, D, E)

Free light chain assay with kappa/lambda ratio

Urine immunofixation & protein

electrophoresis (UPEP+IFE)

What it means

Hemoglobin, WBC, Platelets

Creatinine, Calcium, Albumin, Liver function

Part of staging and risk stratification

Measures the level of normal and clonal protein

Identifies the type of clonal protein

Measures the level of normal and clonal protein

Identifies the type of clonal protein

This

CBC= Complete Blood Count; WBC = White Blood Cell

Rajkumar SV, et al. Lancet

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

Oncol. 2014;15:e538-3548. Ghobrial IM, et al. Blood. 2014;124:3380-3388; mSMART.org; NCCN.org S L i

R A B

Testing For Myeloma: Imaging

Imaging:

–Skeletal survey: Series of X-rays; less sensitive than other techniques

–Whole body low dose (CTWB-LD CT )

–Positron Emission Tomography (PET/CT)

–Magnetic Resonance Imaging (MRI)

Healthy bone versus myeloma bone disease

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

This Photo by Unknown Author is licensed under CC BY-NC-ND S L i M C R A B

Testing For Myeloma: Bone Marrow

Bone marrow biopsy & aspirate

Bone marrow plasma cells (%)

Congo Red staining if concern for AL-Amyloid

Bone marrow genetics

Cytogenetics

Fluorescence in situ hybridization (FISH)

Next generation sequencing (NGS)

High Risk FISH Results*

Deletions Translocations Gain 1p17p(p53del)

*15-20% of people with NDMM

t(4;14) t(14;16) t(14;20)

1q+

Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-3548. Ghobrial IM, et al. Blood. 2014;124:3380-3388; mSMART.org; NCCN.org This Photo by Unknown Author is licensed under CC BY-SA

Image Credit: IMF Patient Handbook

Image Credit: IMF Patient Handbook

Staging and Risk Stratification

International Staging System (ISS)

Stage Result

1 β2M < 3.5 mg/L; serum albumin ≥ 3.5 g/dL

2 β2M < 3.5 mg/L; serum albumin < 3.5 g/dL; or β2M 3.5 to 5.5 mg/L, irrespective of serum albumin

Revised International Staging System (RISS), adding LDH & FISH Stage Result 1

Image Credit: IMF Patient Handbook

β2M > 5.5 mg/L

β2M < 3.5 mg/l Serum albumin ≥

β2M ≥ 5.5

CA = chromosomal abnormalities; LDH = Lactate Dehydrogenase; FISH = Fluorescence in situ hybridization R2-ISS Risk Scoring System Stage Score Low 0 Low-Intermediate 0.5-1.0 Intermediate-High 1.5-2.5 High 3-5 Risk Feature R2-ISS Score ISS-2 1 ISS-3 1.5 1q+ 0.5 del(17p) 1 t(4;14) 1 LDH, High 1

3.5 g/dl Standard-risk CA by FISH Normal LDH 2 Not R-ISS stage I or III 3

mg/L and either High-risk CA by FISH OR High LDH

Myeloma Treatment Schema

Transplan

t Eligible Patients

Transplan t

Ineligible Patients

Initial Therap y

Transplant (ASCT) Maintenan

ce Treatme nt of Relapse d disease

Consolidation / Maintenance

Continued therapy

Everyone

Supportive Care

HCP Clinical Experience

TREATMENT DECISION

Your Preference

Research Results

Philippe Moreau. ASH 2015.

ASCT = Autologous Stem Cell Transplant

Drug Class Overview

IMiD

immunomodulatory drug

Pomalyst (pomalidomide) P or Pom

Revlimid (lenalidomide) R, Rev, Len

Thalomid (thalidomide) T or Thal

Oral (PO)

Proteasome inhibitor Velcade (bortezomib) V or Vel or B SC/SQ or IV IV

Kyprolis (carfilzomib) C or K or Car

Ninlaro (ixazomib) N or I Oral

Chemotherapy

Steroids

Monoclonal Antibodies

Cytoxan (cyclophosphamide) C, CTX Oral IV

Alkeran or Evomela (melphalan) M or Mel

Decadron (dexamethasone) Dex or D or d Oral IV

Prednisone P or Pred

Darzalex (daratumumab)

Sarclisa (isatuximab)

Empliciti (elotuzumab)

Dara Isa Elo

IV or SQ IV IV

XPO1 Inhibitors Xpovio (selinexor) X or Sel Oral

Class Drug Name Abbreviation Administration

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

Drug Class Overview

Peptide Drug Conjugate* Pepaxto (Melphalan Flufenamide) Melflufen IV

BCMA Targeted Antibody Drug Conjugate (ADC)* Blenrep (belantamab mafodotinblmf) Bela, Belamaf, or B IV CAR T Cell therapy

Bispecific Antibodies

Pipeline

Abecma (idecabtagene vicleucel) Ide-cel IV

Carvykti (ciltacabtagene vicleucel) Cilta-cel

Tecvayli (teclistimab)

Talvey (Talquetamab)

Elrexfio (Elranatamab)

Tec Talq Elra SC/SQ

Cevostamab, Iberdomide, Mezigdomide, Venetoclax Linvoseltamab, LCAR-B38M …………………………………….. MORE TO COME!

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

Class Drug Name Abbreviation Administration

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

Measuring Disease Response: IMWG Response Criteria

R e s p o n s e

Flow MRD negative*

sCR

Molecular CR CR

VGPR PR MR SD PD

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

mCR AND normal Free Light Chain ratio, Bone Marrow negative by flow, 2 measures

CR AND negative PCR

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

Very Good Partial Response: 90% reduction in myeloma protein

Partial Response: at least 50% reduction in myeloma protein

Minimal Response

Stable Disease: Not meeting above criteria

Progressive Disease: At least 25% increase in identified myeloma protein from lowest level

MRD = Minimal Residual Disease

sCR = Stringent Complete Response; BM = Bone Marrow

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

M y e l o m a C e l l s & P r o t e i n

When Do I Need A New Treatment?

Biochemical or Symptomatic Progression/Relapse

Not every relapse requires immediate therapy

Each case is different

Symptomatic or extramedullary disease

Asymptomatic high-risk disease or rapid doubling time or extensive marrow involvement

Initiate Treatment

Asymptomatic biochemical relapse on 2 consecutive assessments

Consider Treatment

Patient-/Disease-Specific Monitor Carefully

Consider Observation

Monitor Carefully

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

Targets on the Myeloma Cell Surface and Therapeutic Antibodies

Bi-Specific Antibodies

Talquetamab

CAR-T

Antibody Drug

Elotuzumab

Bi-Specific Antibodies

Bi-Specific Antibodies CAR-T

Antibody Drug

Daratumumab and Darzalex Faspro

Isatuximab

TAK-079

MOR202

Immune Therapies

Ide-cel CAR-T

Cilta-cel CAR-T

Teclistamab

Other CAR-Ts

Other Bi-Specific Antibodies

BCMA CD38 GPRC

SLAMF7 FcRH5

Antibody Drug Conjugates

How it works:

An antibody directed at a target (BCMA) combined with a cytotoxic agent (chemotherapy)

ADC = Antibody-Drug Conjugate

BCMA = B-Cell Maturation Antigen

ADCP/ADCC = Antibody-Dependent Cellular

Cytotoxicity & Phagocytosis

Image

Credit:

https://creativecommons.org/licenses/by-nc/3.0/

The Process of CAR T Cell Therapy

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

MM with 4

T therapy recommended.

ready to

Apheresis to collect T Cells T Cells Bridging therapy, if needed; Lymphodepleting therapy when CAR T cells are ready CAR T= Chimeric Antigen Receptor T Cell; LOT = Lines of Therapy TCellInfusion Close monitoring and Management of side effects 1

4 5 HOME!

Relapsed

prior LOT CAR

Insurance approved and

move forward.

3 2a 2b

Bispecific Antibodies: Mechanism of Action

• Incorporates 2 antibody fragments to target and bind both tumor cells and T cells

• Brings target-expressing MM cells and T cells into close proximity, enabling T cells to induce tumor-cell death

Antibody-Drug

Targets of Bispecific Molecule Vary

“Off the Shelf” Advantage

• No manufacturing process, unlike CAR T-cell therapy (but like ADC/belantamab therapy)

• Thus, no delay between decision to treat and administration of drug

Source:

License:

4.0. Barilà

et al. Pharmaceuticals (Basel)

Agent

T-Cell Target

Image

Shah N, et al. Leukemia. 2020;34:985–1005. Creative Commons

CC BY

. 2021;14(1):40.

Tumor Cell Target

Teclistamab Elranatamab BCMA CD3 Talquetamab GPRC5D CD3 Cevostamab FcRH5 CD3

ADC = Conjugate; BCMA = B-Cell Maturation Antigen; CD3 = Cluster of Differentiation 3; FcRH5 = Fc receptor-homolog 5; GPRC5D = G-protein coupled receptor family C group 5 member D

The Evolution of Myeloma Therapy

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

CAR T Cell Therapy

Bispecific/Trispecific Antibodies

Cell Modifying Agents

Venetoclax

PD/PDL-1 Inhibition?

Small Molecules

New

Induction Consolidation Front line treatment Post consolidation Maintenance Rescue Relapsed

Now

ASCT, autologous stem cell transplant; CAR, chimeric antigen receptor; Cy, cyclophosphamide; d- daratumumab; D/dex, dexamethasone; isa, isatuximab; K, carfilzomib; M, melphalan; PDL1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib.

Speaker’s own opinions.

What about Disease Control and Cure in Myeloma?

Biochemical or Symptomatic Progression/Relapse

 Control is the immediate priority with active disease

 Cure remains the overall goal

Defining “Cure” has many considerations:

 Minimal Residual Disease Negative (MRD-)

 Time Off Therapy

 Functional Cure

Active Disease

Requiring Treatment

Stable or Unmeasurable Disease, Receiving Treatment

Unmeasurable Disease, Receiving No Treatment

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

dated 2.15.2024

Resources Myeloma.org

Thank you

EVALUATION

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

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

We greatly appreciate your time and feedback!

Advanced Care Planning

Wendy Thomas, RN, MSN, CHPN University of Kansas Cancer Center

03/15/2024 56

KC Area Support Group Leader

Advance Care Planning

Wendy Thomas, RN, MSN, CHPN

CHPN

• Outpatient Palliative Care Nurse Navigator

• Kansas City Area Myeloma

Support Group Leader

About me:

• Nurse 27 years

• 14 years in blood and marrow transplant

• 8 years in palliative care

• 10 years as a myeloma support group leader

• Worked for the University of Kansas Health System for 17 years

• Based at the Bloch Cancer Care Pavilion, Westwood Kansas

03/15/2024 58

Wendy Thomas, RN MSN

Advance Care Planning

What is Advance Care Planning?

• Discussing and preparing for future medical care decisions

• Important at any stage of life

• Crucial for anyone with a serious illness

03/15/2024 59

Do you have an Advance Directive?

• Who would you want to speak for you if you were unable to speak for yourself?

• Do your family/loved ones know what your wishes would be in a healthcare emergency?

• Do you know what your wishes would be?

03/15/2024 60

Advance Care Planning DPOA & Healthcare Directive 03/15/2024 61

What are your wishes?

Code Status

• What is a Code Status?

– Cardiopulmonary Resuscitation or CPR

• Why do they keep asking?

– Code status expires at discharge

– Out of hospital DNR

– Living will

• How aggressive do you want care to be?

– ICU

– Mechanical Ventilation

– Medically administered nutrition

03/15/2024 62

Deciding about CPR

CPR

• No pulse, not breathing

• One of the few treatments that patients to NOT have performed

• A physician order is REQUIRED to NOT perform CPR

• Older people and people with cancer may have survival & quality of life after CPR

• You can CHOOSE to allow a NATURAL prefer

03/15/2024 63

Level of Medical Interventions?

Pulse present &/or still breathing

• Full treatment

ICU and intubation with mechanical ventilation

• Midlevel treatment

Antibiotics, fluids, medication to support blood pressure

• Best supportive care

Treat with dignity and respect, comfort-focused medical treatment

03/15/2024 64

Out of hospital DNR

• Patients should complete with physician

• Requires physician signature

• Original form stays with patient

• Copy should be provided to all of your healthcare providers/health systems

• Some states have transportable DNR laws

03/15/2024 65

What to do with Forms & Documents?

• Make certain your family/loved ones know the location

• Give a copy to your healthcare providers/health systems

• Easy to find in case of emergency

• These documents DO NOT belong in your safe deposit box

03/15/2024 66

Other Practical issues

Planning ahead

• Eases the burden for family/loved ones

• Protects your assets

• Allows you to manage your personal effects

New Complications

• The electronic era brings new challenges

• Cellphones, computers, online accounts, social media and photos

03/15/2024 67

The Most Important Part

Talking with your loved ones about your healthcare wishes

03/15/2024 68

03/15/2024 69

EVALUATION

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

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

We greatly appreciate your time and feedback!

Financial Considerations in Myeloma

Amanda Goodstadt, Esq.

Triage Cancer

Financial Considerations in Myeloma

Amanda Goodstadt, Esq. Senior Staff Attorney, Triage Cancer

This presentation provides general information on the topics presented. The authors and presenters are not engaged in rendering any legal, medical, or professional services by its presentation or distribution. Although this content was reviewed by a professional, it should not be used as a substitute for professional services.

No part of this presentation may be reproduced, distributed, or transmitted in any form or by any means, without the prior written permission of the author, except properly attributed, noncommercial uses permitted by copyright law. For permission requests, contact the authors at info@triagecancer.org

Triage Cancer is a national, nonprofit organization that provides free education on the legal and practical issues that may impact individuals diagnosed with cancer and their caregivers.

About Triage Cancer

Triage Cancer’s Free Resources

• TriageCancer.org

• Educational Events

• Triage Cancer Conference: 5/17 & 5/18

• Live & Recorded Webinars

• CancerFinances.org

• Quick Guides & Checklists

• Animated Videos

• State Resources & Chart of State Laws

• Legal & Financial Navigation Program

Contributors to Financial Toxicity

• Health Insurance Status

Financial Health Factors That Tip the Scale

• Adequate coverage

• Effective navigation of policies

• Consumer Protections

• Medical Bills

• Employment Changes

• To work or not to work - accommodations

• Disability Insurance

• Life Changes

• Marriage/divorce, moving, graduating from school, etc.

Not

Understand Health Insurance?

Don’t

You Are

Alone. Source: 2017 PolicyGenius Health Literacy Survey

How much time do Americans spend reviewing their health insurance options?

< 30 minutes

< 20 minutes

“As fast as I can!”

> 2 hours per day!

Knowing How to Use Your Health Insurance

Health Insurance Terms: Costs

Cost to Have Health Insurance

• Premium – each month (fixed $ amount)

Costs When You Use Your Health Insurance

• Deductible – each year (fixed $ amount)

• Co-Payment – each time you get care (fixed $ amount)

• Co-Insurance or Cost-Share – each time you get care (%)

• Out-of-Pocket Maximum (fixed $ amount) =

deductible + co-payments + co-insurance

Meet Dan

Dan’s Plan: Deductible = $2,000 Co-insurance = 80/20 plan

OOP Max = $8,000

If Dan has a $102,000 hospital bill, what does he pay?

1. His deductible of $2,000 $102,000-$2,000 = $100,000 left

2. His co-insurance amount of 20% 20% of $100,000 = $20,000

But OOP max is $8,000. So, he would only pay the $2,000 deductible + $6,000 of the $20,000 co-insurance amount, for a total of $8,000.

There may be a separate out-of-pocket maximum for out-of-network services

Individual vs. Family Plans

• e.g., Individual $5,000 and Family $10,000

Marketplace Plans

•Out-of-pocket max = deductible + co-payments + co-insurance (medical care & drugs)

Some Employer Plans

• Doesn’t include deductibles

• Out-of-pocket max = co-payments + co-insurance

• Doesn’t include deductibles or co-payments

• Out-of-pocket max = co-insurance

• Doesn’t include prescription drugs

• Separate out-of-pocket max for prescription drugs = co-payments + co-insurance

Out-of-Pocket Maximums

Details . .

Medicare

As of September 2023: covers more than 66 million people (~20% of U.S. population)

• Eligibility

• U.S. Citizen or legal resident

• Legal residents = live in U.S. for at least 5 years in a row, including the 5 years just before applying

• And be:

• 65+ years old; or

• Receiving SSDI 2+ years; or

• Have ESRD or ALS

Medicare Options: Pick a Lane

Lane 1: Original Medicare

Do you want an Rx plan (Part D)?

Do you want a Medigap plan?

Lane 2: Medicare Advantage (Part C)

Do you also need a Rx plan (Part D)?

Has OOP Max

Medicare Part D 2024 After the ACA

Beneficiary pays $545 deductible out of pocket

After total out-of-pocket drug costs* = $8,000**

Beneficiary pays 25%

Beneficiary pays nothing

Medicare pays 75%

Medicare pays 100%

*Includes certain payments made on behalf of the beneficiary (e.g., drug company discounts)

**Actual OOP if taking only brand-name drugs ~$3,300

Initial Coverage Deductible Catastrophic Coverage

Inflation Reduction Act of 2022

• 2024: Eliminates 5% catastrophic coverage payments (total oop drug costs capped at $8000)

• 2025: Caps out-of-pocket drug costs at $2,000

• Applies to both Part D plans and Part C plans with drug coverage

• Currently, no cap for Part D & Part C out-of-pocket max does not include drugs!

• If plan has a drug deductible, that will count towards the cap

• Cap could increase over time

• 2025: Part D plans will allow out-of-pocket costs to be spread out through the year, rather than a lump sum payment (e.g., in January)

Medicare Part D

Medicaid

• Federal program

• Provides free or low-cost health insurance coverage

• As of 9/23: 88.4 million people on Medicaid & CHIP (~1 in 4 Americans)

• Federal – state funding partnership

• State administration

• State waivers to customize program

Medicaid as of 1/1/14

Eligibility: low income + low resources +

Adults with household income under 138% of FPL

“Aged, Blind, Disabled”

Minor kids or people with minor kids

Pregnant women for 6-12 months after baby’s birth

Breast & Cervical Cancer Treatment

State Medicaid Expansion 2024

Updated: 2/9/2024 (info changes frequently, please check for updates)

1 MI expansion began 4/1/14

2 PA expansion began 1/1/15

3 NH expansion began 1/1/16

4 IA & AR implemented expansion through premium assistance & wrap around Medicaid

5 AK expansion began 9/1/15

6 MT expansion began 1/1/16; reauthorized with work requirement from 1/1/20-12/31/24 – waiting for fed approval

7 LA Governor signed EO for expansion; began 7/1/16

8 ME expansion began 2/1/19; coverage retroactive to 7/2/18

9 VA expansion began 1/1/19

10 UT full expansion began 1/1/20

11 ID expansion began 1/1/20

12 NE expansion begins 10/1/20

13 OK voters approved a ballot measure 6/20 to expand 7/1/21

14 MO voters approved a ballot measure 8/4/20 to expand 7/1/21, court reinforced expansion requirement

15 SD voters approved a ballot measure 11/22 to expand 7/23

16 NC expansion began 12/1/23

TriageCancer.org/Medicaid-Expansion

Expanded 41 Not Expanded 10 AK5 , AR4 , AZ, CA, CO, CT, DC, DE, HI, IA4 , ID11 , IL, IN, KY, LA7 , MA, MD, ME8 , MI1 , MN, MO14 , MT6 , ND, NE12

NH3

NJ, NM, NV, NY, NC16

OH, OK13

OR, PA2

VA9

, RI, SD15 , UT10 ,

, VT,

State Health Insurance Marketplaces

• “Exchanges” = insurance shopping mall

• Benefits:

• Cap on OOP max: $9,450 individual / $18,900 family (2024)

• Financial help

• Premium tax credits

• Cost-sharing subsidies (aka “reduction”)

Ins. Company

Government: Medicare, Medicaid, Military, State & Local Programs, etc.

Employer

Marketplace Plan Options

Standardized cost-share:

Catastrophic coverage (under 30)

Additional Financial Help Now Available

Cost-Sharing Subsidies

Note: Eligibility for 2024 premium tax credits based on 2023 FPL

Will continue through 2025 under IRA

400% + (2023) $ help  reduce monthly premiums to 8.5% of household income

Premium Tax Credits Medicaid

(Silver Plans Only)

Househo ld Size 100% (2024) 138% (2024) 150% (2024) 250% (2023) 400% (2023) 1 $15,060 $20,782.8 $22,590 $36,450 $58,320 2 20,440 28,207.2 30,660 49,300 78,880 3 25,820 35,631.6 38,730 62,150 99,440 4 31,200 43,056 46,800 75,000 120,000 5 36,580 50,480.4 54,870 87,850 140,560 6 41,960 57,904.8 62,940 100,700 161,120 © 2024 Triage Cancer® 93

When to Enroll?

• Employer plans: varies (often in the Fall)

• Medicaid: accepted year round

• Medicare: Oct. 15 – Dec. 7*

• Marketplace: Nov. 1 – Jan. 15*

• Enroll by Dec. 15 for coverage that starts Jan. 1

• Some states may have longer open enrollment periods (e.g., CA and NJ until Jan. 31)

*Plans are for a calendar year

Comparing Plan Options

Employer

Marketplace Plan 1 Marketplace Plan 2

Plan 1

Plan 2 Marketplace Plan Employer Plan Medicare Advantage Plan 1

Medicare Advantage Plan 2

Total Annual Cost

Bronze: Monthly Premium Deductible Out-of-pocket Maximum $200 $6,000 $8,000 © 2024 Triage Cancer® 96 Silver: Monthly Premium Deductible Out-of-pocket Maximum $275 $2,500 $6,000 Platinum: Monthly Premium Deductible Out-of-pocket Maximum $400 $0 $2,000

Do the Math!

Note: for in-network providers only

Total possible costs for year = 12 months of premiums + OOP max

#1: $200x12 = $2,400

+ OOP = $8,000

Total = $10,400

#2: $275x12 = $3,300

+ OOP = $6,000

Total = $9,300

#3: $400x12 = $4,800

+ OOP = $2,000

Total = $6,800

Bronze: Monthly Premium Deductible Out-of-pocket Maximum $200 $6,000 $8,000 Silver: Monthly Premium Deductible Out-of-pocket Maximum $275 $2,500 $6,000 Platinum: Monthly Premium Deductible Out-of-pocket Maximum $400 $0 $2,000

Key Considerations

• Cost

• Premiums, co-payments, deductibles, co-insurance, out-ofpocket maximums

• Network of providers and facilities

• Check if your providers and facilities (hospitals, labs, imaging centers, etc.) are covered

• Prescription drug coverage

• Which drugs are covered (i.e., formulary)?

• Is there a separate out-of-pocket maximum for drugs?

Communications Post-treatment

• From your insurance company:

We have received a claim

We are processing your claim

Explanation of Benefits

Managing Medical Bills

•

From your provider:

• The bill

• Doesn’t always happen in this order!

• Wait for the EOB before paying any bills

• Keep track and communicate with providers

• Ask questions

• Do you qualify for hospital charity care?

• Apply for help from Dollar For:

https://dollarfor.org/Triage Cancer

• Appeal denials

Reviewing Medical Bills

• Review bills for accuracy

• Don’t be afraid to ask your provider to clarify codes!

• Medical procedure billing codes: CPT (Current Procedural Terminology) codes, www.nlm.nih.gov/research/umls/sourcereleasedocs/current/CPT/sourcerepresentation.html

• Medical diagnosis codes: International Classification of Diseases (ICD) codes, www.who.int/standards/classifications/classification-of-diseases

• Review EOBs

• Tips on reading EOBs: https://nhhealthcost.nh.gov/guide/question/how-do-i-read-explanation-benefits-eob

• Consider professional bill reviewer/medical claims org

• Alliance of Claims Assistance Professionals (ACAP) www.claims.org

Consumer Protections: Appeals

• Denials of coverage (aka “adverse benefit determination” (ABD))

• Internal appeals

• External appeals (individual and employer plans)

• AKA: Independent or External Medical Review

• Conducted by an independent medical review organization (IRMO) or independent review entity (IRE)

• State Health Insurance Agency: Triagecancer.org/StateResources

• Cost: $0 if HHS process. Up to $25 if issuer contracts with IRO or uses state process

Hurdle: Knowledge

Health Insurance Appeals Resources TriageCancer.org/HealthInsurance

Quick Guide to Appeals for Employer-Sponsored & Individual Health Insurance

Quick Guide to Access to Medical Records

Health Insurance Appeals Tracking Form

CancerFinances.org – Health Insurance Appeals Module

Recorded Webinar: Health Insurance Appeals

•

Think Creatively About Financial Assistance

Triage Cancer Conferences

Educational events for:

• Individuals diagnosed with cancer

• Caregivers

• Health care professionals

•Advocates & others Topics:

• Being an Advocate

• Health Insurance

• Finances

• Being Prepared

• Employment

Online: May 17 & 18 October 25 & 26

TriageCancer.org/Conferences

*Free CEs/Contact Hours for nurses, social workers, & patient advocates

*Free PDCs for HR professionals

Triage Cancer Webinar Series

Upcoming Topics:

• February 27 ~ Managing Medical Bills & Getting Financial Help

• March 26 ~ Improving Access to Fertility Preservation

• April 30 ~ Estate Planning

Full Schedule & Registration: TriageCancer.org/Webinars

Recordings of Past Webinars: TriageCancer.org/Past-Webinars

*Free Contact Hour/CE for nurses, social workers, & patient advocates

*Free PDCs for HR professionals

Free, one-on-one help for:

• Individuals diagnosed with cancer

• Caregivers

• Health care professionals

Health Insurance, Employment, Disability Insurance, Finances, Estate Planning, & More

Our Navigation services:

• Explain options

• Provide accurate information

• Empower you to take next steps

Start Online:

TriageCancer.org/GetHelp

For Spanish:

TriageCancer.org/ConsigueAyuda

Legal & Financial Navigation Program

to share your experience or visit TriageCancer.org/Testimonials

Scan

EVALUATION

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

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

We greatly appreciate your time and feedback!

11 4

Clinical Trials

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

Foundation

Professor, Translational Genomics Research Institute, City of Hope Cancer Center

Objectives

• Provide the rationale for clinical trials

• Outline the phases of clinical trials

• Discuss the risks and benefits of clinical trials

• Listen to patients who have been on a clinical trial

Clinical Trials - Overview

Remember 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

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 Are Cancer Clinical Trials Important?

• Clinical trials translate results of basic scientific research into better ways to prevent, diagnose, or treat cancer

• The more people that take part, the faster we can:

• Answer critical research questions

• Find better treatments and ways to prevent cancer

119

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!

Even Before Phase I

• Most agents are tested in lab models

• Various “myeloma cell lines” = in vitro

• Next step is animal model

• We are more like mice than you think!!

• Earliest study in phase I is called “First in Human”

• Often uses extremely low dose of drug to ensure safety

Clinical Trials - Phases

Phase I Phase II Phase III

Tests safety Tests how well treatment works Compares new treatment to standard treatment

Phase 1 Clinical Trials

• All patients receive the experimental therapy

• Phase 1 trials find the optimal dose of a new drug or drug combination

• Patients get higher doses as the study continues

• Determine side effects of new drugs or combinations

• Explore how the drug is metabolized by the body

• Important for all stages of myeloma

Phase 2 Clinical Trials

• Determine if a new drug or combination is effective against the cancer

• May be added to a phase 1 study once the ideal dose is found

• Patients usually receive the experimental therapy

• In some cases, the study may include two “arms” comparing either two different doses or a different treatment (another combination of drugs)

Phase 3 Clinical Trials

• Highest form of clinical evidence. Typically a large number of patients are required…usually required for full FDA approval

• Patients receive either an experimental therapy (one or more drugs) or the current standard treatment

• The patient is randomly assigned to a treatment—a process called randomization

• Neither the physician or the patient can determine which treatment is given

• May be placebo controlled, if no standard treatments are available

• Very closely monitored for effectiveness and side effects

Clinical trial study design or protocol

•

Each cancer clinical trial has a written detailed study design called a protocol that includes:

• Why the clinical trial is needed

• Purpose of the clinical trial

• What drug or drug(s) are being tested, with a treatment and follow-up schedule

• Safety measures throughout the clinical trial program

• How outcomes will be measured

• Who is eligible for the clinical trial

• How the clinical trial will be organized, one site or multiple sites

• If the clinical trial is a multi-site trial, all participating physicians must follow the same protocol

Benefits of Participation

Possible benefits:

• Patients will receive, at a minimum, the best standard treatment

• If the new treatment or intervention is proven to work, patients may be among the first to benefit

• Patients have a chance to help others and improve cancer care

127

Risks of Participation

Possible risks:

• New treatments or interventions under study are not always better than, or even as good as, standard care

• Even if a new treatment has benefits, it may not work for every patient

• Health insurance and managed care providers do not always cover clinical trials

128

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

129

Diversity in Clinical Trials

• There has been a lack of diverse representation in clinical trials in myeloma. In the U.S., approximately 20% of all myeloma patients are of African descent, but only 5%–8% of patients in myeloma clinical trials are of African descent.

• This is significant for the following reasons:

All patients of all races and ethnicities should be able to benefit from clinical trials.

Diverse patient representation in clinical trials is required to ensure that the outcomes are applicable to all patients.

• Reasons for underrepresentation in clinical trials are complex and include systemic racism, accessibility of clinical trials, sensitivity to diversity by medical professionals, misconduct in medicine in the past, the lack of trust in the system, and more.