IMF Virtual Regional Community Workshop (RCW) - Northeast and Southern Region

Welcome!

Thank you for joining us today for the February 1, 2023, International Myeloma Foundation’s Regional Community Workshop –Northeast & Southern states.

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IMF REGIONAL COMMUNITY WORKSHOP

February 1, 2023, Agenda

5:30 – 5:35 PM Welcome and Announcements

Kelly Cox, Senior Director Regional Community Workshops

5:35 – 6:10 PM Myeloma 101 & Frontline Therapy

Craig Cole, MD - Michigan State University

6:10 –

6:25 PM Q&A with Panel

6:25 –

6:35 PM Guided Meditation & Stretch Break

6:35 –

7:15 PM Relapsed Therapy & Clinical Trials

David Vesole, MD, PhD, FACP - The John Theurer Cancer Center at Hackensack University Medical Center

7:15 – 7:35 PM Life is a Canvas, You are the Artist

Kimberly Noonan, DNP, ANP-BC, AOCN - IMF Nurse Leadership Board, Dana-Farber Cancer Institute

7:35 – 8:00 PM Q&A with Panel

Myeloma 101 and Frontline Therapy Craig Cole, MD Michigan State University

The Application of Science: Multiple Myeloma 101 and Frontline Therapy

International Myeloma Foundation

Regional Community Workshop

Wednesday, February 1st, 2023

Craig Emmitt Cole, M.D. Assistant Professor Director of

Clinical Research

Department of Internal Medicine

Division of Hematology/Oncology; Hematology Section

Michigan State University College of Human Medicine

Karmanos Cancer Institute

Today’s Discussion

 How common is multiple myeloma

 Spectrum of plasma cell disorders

 Diagnosis of myeloma and labs

 Staging and risk stratification

 The Science behind the treatments!

 Up front therapy strategies: induction, transplant, and maintenance

 Bone support

 “New Stuff” 4 drug induction therapy

 Perspectives in the advancement of myeloma science and survival

Multiple Myeloma is a Cancer of the Bone Marrow Plasma Cells

BLOOD

• Myeloma is a cancer of the blood

• Myeloma crowds out normal blood forming cells, causing anemia

Normal plasma cells

Antibodies

Calcium high

Renal (kidney) failure

Anemia

Bone destruction

BONES

• Surrounding bone where Myeloma cells grow is damaged/ weakened

• Myeloma cells activate bone destruction  blood calcium levels

Bone

Mutated Cancer Cell

Monoclonal (M) proteins

Bone marrow

Multiple Myeloma cells

Large amounts of M proteins

Common Symptoms Multiple Myeloma

Low Blood Counts

• Anemia is present in 60% at diagnosis

• May lead to anemia and infection

Decreased Kidney Function

• Occurs in over half of myeloma patients

Bone Damage

• Affects 85% of patients

• Leads to fractures

Bone Turnover

• Leads to high levels of calcium in blood (hypercalcemia)

About 10% to 20% of patients with newly diagnosed myeloma will not have any symptoms.

C: Calcium elevation (>11 mg/dL)

Weakness

Fatigue

Infection

Weakness

Bone pain

Loss of appetite

Weight loss

R: Renal- low kidney function; (serum creatinine >2 mg/dL)

A: Anemia –low red blood count (Hb <10 g/dL)

B: Bone disease (≥1 lytic lesions on skeletal radiography, CT, or PET-CT)

Spectrum of Plasma Cell Disorders and Myeloma

MGUS

Monoclonal Gammopathy of Uncertain Significance

M protein under 3 g/dL AND Plasma cells in Bone Marrow <10% AND No CRAB or “SLiM” high risk features

Smoldering Myeloma

M protein over 3 g/dL (serum) or over 500 mg/24 hrs (urine) AND Plasma cells in Bone Marrow 10%–60% AND No CRAB or “SLiM” high risk features

High Risk Smoldering

Multiple Myeloma

M protein over 2 g/dL AND Plasma cells in Bone Marrow 20%–60% AND Free Lt Chain Ratio >20

“Evolving type”SMM Increase >10% protein w/in 6mo AND No CRAB or “SLiM” high risk features

Malignant Plasma cells seen on any biopsy (usually bone marrow) AND ≥1 “CRAB” feature

C: Calcium elevation (>11 mg/dL)

R: Renal- low kidney function; (serum creatinine >2 mg/dL)

A: Anemia –low red blood count (Hb <10 g/dL)

B: Bone disease (≥1 lytic lesions on skeletal radiography, CT, or PET-CT)

OR have >1 SLiM ‘high risk” features:

S: >60% Plasma Cells on Bone Marrow biopsy

1% risk of progression/year to multiple myeloma or related conditions

10% risk of progression/year to active myeloma

>46% risk of progression in 2 yr to active myeloma

Li: Serum light chain ratio >100

M: >1 lytic lesions on MRI (or PET/ CT scan)

Front Line Treatment

Diagnosing Myeloma: Learn Your Labs!

CBC • Number of red blood cells, white blood cells, and platelets

CoMP

• Measure levels of albumin, calcium, and creatinine. Assess function of kidney, liver, and bone status (alkaline phosphatase) and the extent of disease.

Beta2 MicroG

LDH Lactate Dehydrogenase

Serum Protein EP

Immuno Fixation

Serum FreeLight Chain

Urine Protein EP

• Determine the level of a protein that indicates the presence/extent of MM and kidney function: USED FOR STAGE

• Determine the level of myeloma cell production and extent of MM : USED FOR STAGE

• Detect the presence and level of M protein = how much myeloma

• Identify the type of abnormal antibody proteins: IgG, IgA, κ,or λ

• Freelite test measures free light chains (kappa or lambda) in blood = how much myeloma

• Detect Bence-Jones proteins (otherwise known as myeloma light chains) in urine (present or not present)

24 hr Urine Analysis

• Determine the presence and levels of M protein and Bence Jones protein in the urine = how much myeloma

Serum Protein EP

Monoclonal protein

• Detect the presence and level of M protein = how much myeloma

Treatment

Serum FreeLight Chain

Treatment

• Freelite test measures free light chains (kappa or lambda) in blood = how much myeloma

Positive Kappa

Monoclonal Serum

Kappa Lt. Chain MM

Kappa Lt. Chain

Lambda Lt. Chain

Light Chains

Ratio: 1

Types of Monoclonal Protein (M Protein) in Multiple Myeloma

• IgG+kappa

• IgG+lambda

• IgA+kappa

• IgA+lambda

• etc…

• 80% of myeloma cases

Jones protein

• 18% of all myeloma cases

• Renal failure more common in light chain multiple myeloma; creatinine >2 mg/dL in 1/3 of cases

protein present

• Less than 3% of cases of multiple myeloma

Diagnosis of Multiple Myeloma

• Conventional X-rays reveal punched-out lytic lesions, osteoporosis, or fractures in 75% of patients.

• FDG PET/CT appears to be more sensitive (85%) than skeletal survey for the detection of small lytic bone lesions.

• Diagnosis is confirmed with bone marrow demonstrating greater than 10% involvement by malignant plasma cells with either CRAB or SLiM

Malignant Plasma cells seen on biopsy

AND ≥1 “CRAB” feature

C: Calcium elevation (>11 mg/dL)

R: Renal- low kidney function; (serum creatinine >2 mg/dL)

A: Anemia –low red blood count (Hb <10 g/dL)

B: Bone disease (≥1 lytic lesions on skeletal radiography, CT, or PET-CT)

OR have >1 SLiM ‘high risk” features:

S: >60% Plasma Cells on Bone Marrow biopsy

Li: Serum light chain ratio >100

M: >1 lytic lesions on MRI (or PET/ CT scan)

Staging Myeloma: The Importance of Genomic Testing

DNA

Conventional cytogenetic analysis (karyotyping)

FISH

(fluorescence in situ hybridization)

Advances

• Genetic expression profiling [GEP]

• Whole-genome/ whole-exome sequencing

• Plasma cell next generation sequencing

Staging Myeloma: FISH helps to Assign Risk in Myeloma

Risk Category

Findings on Chromosome (FISH) Analysis Results in the Bone marrow

High Risk

FISH:

• Deletion 17th chromosome

• Gain of chromosome 1q

• Translocation 4 and 14

FISH:

Standard Risk

• Hyperdiploid: More than 1 pair of chromosomes (Trisomies)

• Translocation 11 and 14

• Translocation 6 and 14

• Translocation 14 and 16

• Translocation 14 and 20

NGS: p53 mutation (on chrom 17)

• Double Hit Myeloma: 2 high risk

genetic abnormalities

• Triple Hit Myeloma: 3 or more high risk genetic abnormalities

• Others

• Normal

Revised International Staging System for Multiple Myeloma

From International Myeloma Working Group

Stage 1

β2-microglobulin under 3.6 mg/L Normal Lactate

Dehydrogenase (LDH)

AND

Stage 2

Stage 3

β2-microglobulin over 5.5 mg/L

Does not meet Criteria for Stage 1 or 3

HIGH Lactate

Dehydrogenase (LDH)

AND

High Risk

Cytogenetics

(FISH)

Deletion 17 chromosome

Translocation 4th and 14th

Translocation 14th and 16th

Translocation 14th and 20th

Immunomodulatory Drugs ( Thalomid(Thalidomide), Revlimid(Lenalidomide

Proteasome Inhibitors (Pis):

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

Antibodies Against Myeloma (Immunotherapy): Darzelex (Daratumumab), Sarclisa(Isatuximab), Empliciti(Elotuzumab)

IMiDs for Multiple Myeloma

How does it work?-SCIENCE!

• Direct inhibition of DNA synthesis of myeloma cells.

IMiDs for Multiple Myeloma

VEGF bFGF

How does it work?-SCIENCE!

• Direct inhibition of DNA synthesis of myeloma cells.

• Inhibition of blood vessel synthesis in the bone marrow.

IMiDs for Multiple Myeloma

How does it work?-SCIENCE!

• Direct inhibition of DNA synthesis of myeloma cells.

• Inhibition of blood vessel synthesis in the bone marrow.

• Inhibition of adhesion between the myeloma and bone marrow stromal cells.

IMiDs for Multiple Myeloma

IL 6

IL 1β

TNF α

How does it work?-SCIENCE!

• Direct inhibition of DNA synthesis of myeloma cells.

• Inhibition of blood vessel synthesis in the bone marrow.

• Inhibition of adhesion between the myeloma and bone marrow stromal cells.

• Inhibition of the release of the cytokines IL-6, TNF-α, and IL-1β.

IMiDs for Multiple Myeloma

How does it work?-SCIENCE!

• Direct inhibition of DNA synthesis of myeloma cells.

• Inhibition of blood vessel synthesis in the bone marrow.

• Inhibition of adhesion between the myeloma and bone marrow stromal cells.

• Inhibition of the release of the cytokines IL-6, TNF-α, and IL-1β.

• Activation of the body’s natural killer cells (T-cells) which attack the myeloma cells.

Rise of the IMiD Biologic Therapies

 1990s, several thalidomide analogs were synthesized to increase efficacy and minimize toxicity.

 2006 FDA approves Lenalidomide (Revlimid).

 Revlimid is felt to be 50 to 2000 more potent than thalidomide.

 Phase 2 trial 91% new myeloma achieved responses with Lenalidomide plus dexamethasone.

 2013 FDA approves Pomalidomide.

 Pomalyst and dexamethasone given to multi-refractory myeloma with response rates of 35 to 65%.

 Combination of pomalidomide, bortezomib, and dexamethasone in relapsed MM response rates of 72%.

 Iberdomide (CC-220) is the newest in the class and is now in clinical trials

 CELMODs are the next class of IMiD with CC92480 drug more potent than iberdomide

Rise of the Proteasome

Rise of the Proteasome

Proteasome

Rise of the Proteasome

Rise of the Proteasome

• Bortezomib(velcade) approved by the FDA in 2003 in patients with relapsed refractory myeloma.

• Several phase 2 trials in newly diagnosed myeloma with bortezomib-dexamethasone induction.

o Responses 66% to 90%, including 15% to 21% Complete Responses!

• 2012 FDA approves Carfilzomib(Kyprolis); secondgeneration irreversible Proteasome inhibitor

• In refractory myeloma with 48% response rates. Higher in combination!

• Ixazomib (Ninlaro) is new oral boronated reversible proteasome inhibitor currently approved by the FDA in 11/2015.

Bortezomib(Velcade)

Carfilzomib(Kyprolis)

Ixazomib (Ninlaro)

Targets on the Myeloma Cell Surface and Therapeutic Antibodies

Bi-Specific Antibodies

Talquetamab

CAR-T

Antibody Drug

Elotuzumab

Bi-Specific Antibodies

BCMA

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 Bi-Specific Antibodies

Other CAR-Ts

Manufactured Antibody Targeting of Myeloma

Antibody and Immune System Attack

Increase production of cytoxic macrophages

Complement Protein Attack

Myeloma Cells

Attacking the Myeloma Cell Biology

Inhibition of adhesion between the myeloma and bone marrow stromal cells

Complement Proteins

Natural Killer Cell Good Guys

Manufactured Anti-Myeloma Antibody

Myeloma surface targets

Antibody Receptor

Macrophages Good Guys

Tools of the Trade for Frontline Therapy

Standard Drug Overview

*In Clinical Trials/ not FDA approved

Treatment Sequence and Regimens for Active Myeloma

Frontline treatment Maintenance Relapsed

Induction

• Velcade/Revlimid/Dex:(VRD)

• Velcade/Thalomid/Dex:(VTD)

• Velcade/Cytoxan/Dex:(CyBorD)

• Darzalex/Revlimid/Dex:(DRD)

• Darzalex/Velcade/Melphalan/Dex

• Darzalex/Velcade/Thalidomide/Dex

• Kyprolis/Revimid/Dex(KRD)

• Darzalex/Velcade/Revlimid/Dex: Dara-RVD

• Ninlaro/Revimid/Dex(IRD)

• Clinical trials

Consolidation

Maintenance

• Stem Cell Transplant

• Continue Induction

• Clinical trial

• Revlimid

• Velcade

• Ninlaro

• Observation

• Thalidomide

• Revlimid/Dara

• Clinical trial

Rescue

Dara+Pomalyst+Dex

Kyprolis+Pomalyst+Dex

Cytoxan+Pomalyst+Dex

Ninlaro+Pomalyst+Dex

Elo+Pomalyst+Dex

Elo+Thaliomide+Dex

Dara+Kyprolis+Dex

Kyprolis+Revlimid+Dex

Elo+Revlimid+Dex

Dara+Revlimid+Dex

Dara+Velcade+Dex

Elo+Velcade+Dex

Cytoxan+Kyprolis+Thalidomide+dex

4 drug therapies of novel agents

Ninlaro+Cytoxan+Dex

Velcade+ Cytoxan+Dex

Velcade+ Pomalyst+Dex

Chemotherapy

Selinexor+Dex

Selinexor+Velcade

Selinexor+ Dara

Isatuximab(Sarclisa)+ Pomalyst+Dex

Darzalex Faspro (under skin)

Ide-cel CAR-T (FDA approved 3/26/2021)

Cilta-cel CAR-T (FDA approved 2/28/2022)

Teclistamab (FDA approved 10/25/2022)

CLINICAL TRIALS!

Newly Diagnosed MM

Not Transplant Candidate

High Risk Standard Risk

Revlimid/Velcade/Dex (RVD) or

Dara-Revlimid Dex (Dara-Rd)

9 to 12 cycles

Velcade Based Maintenance of VRD or Continued Dara-Rd Maintenance

Transplant Candidate

Preferred

High Risk

Dara-RVD x 4 cycles

Standard Risk

RVD-light or Dara-RD

Others: D-VMP,D-VTD,RD

9 to 12 cycles

Revlimid Maintenance or Continued DaraRd Maintenance

Other: KRD or Dara-KRD

or Dara-RVD

Early Auto SCT

?Tandem SCT

Velcade (PI) Based Maintenance Continued Dara-Rd Maintenance

https://www.msmart.org/mm-treatment-guidelines

Early Auto SCT

Revlimid Maintenance +/- Dara

Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360-376. v18 //last reviewed June 2020

Delayed Transplant Collect & store Continue Tx for 8m

Revlimid Maintenance +/- Dara

Goals of Therapy: The Iceberg Model of Myeloma

Partial response

50% reduction in M protein

Very good partial response

90% reduction in M protein

immunofixation positive only

Complete remission

No M-protein

immunofixation negative

Minimal Residual Dis

Minimal Residual Dis

Next Generation Molecular testing

Stem Cell Transplant: Fighting Myeloma with the Left Hook!

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

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

End Points of Study and Follow -up

• Primary end point: progression-free survival (time to next relapse)

• Secondary end points included:

• Response rates, overall survival, quality of life, and adverse events

• Follow-up on participant status : median of 6 years

RVD +Stem Cell Transplant vs. RVD without Transplant

Trial of Newly Diagnosed MM RESULTS

• At a median follow up of 76.0 months, the risk of disease progression or death was 53% higher in the RVD alone group than in the transplantation group (P<0.001)

RVD +Stem Cell Transplant vs. RVD without Transplant DETERMINATION

Trial of Newly Diagnosed MM Quality of Life

Global Health Status/QoL, Physical Functioning

What to do After Transplant?

STaMINA: Phase III Study Design

Revlimid Maintenance

RESULTS

• No difference in time to relapse (PFS) or Overall Survival in standard risk patients who have two transplants, consolidation

Melphalan 200 mg/m² IV Stem Cell Transplant

10 mg/day for 3 cycles, then 15 mg/day* (n = 257) Consolidation

Velcade 1.3 mg/m² IV Days 1, 4, 8, 11

Revlimid 15 mg Days 1-15

Revlimid Maintenance

RVD therapy, or just straight to maintenance after first BMT

Dexamethasone 40 mg IV Days 1, 8, 15 Four cycles (n = 254)

• Straight to maintenance is the easiest!

10 mg/day for 3 cycles, then 15 mg/day

• ? If high risk patients benefit from two transplants

Second (Tandem)

Stem Cell Transplant

Melphalan 200 mg/m² IV

Second ASCT (n = 247) Induction regimens

Analysis of the Maintenance Revlimid (Lenalidomide) Trials

• Data from 4 randomized trials of Revlimid (lenalidomide) maintenance vs. no maintenance

– Involving a total of almost 2,000 multiple myeloma patients

• The results of the analysis showed that Revlimid maintenance therapy is associated significant improvement in progression-free survival and a modest improvement in overall survival

• Duration of maintenance is unknown

Bone Support & Control of Bone Pain

Multiple myeloma can cause weakened areas in the bone called osteolytic lesions which can compress the spinal cord or cause bone destruction.

• Bone strengthening drugs: bisphosphonates (pamidronate & Zometa) or monoclonal antibodies (Xgeva) are given at diagnosis and continued for at least 2 years

•

Vitamin-D and Calcium supplements to help bone healing •

Orthopedic support

– Physical therapy, physical medicine consults, orthopedic/neuro surgery, radiation therapy, etc

•

Minimally invasive procedures: kyphoplasty or vertebroplasty

• Use of medication to control pain

• Anticonvulsants and antidepressants for treat relieve pain from nerve damage or numbness

GRIFFIN Randomized Phase II: Dara-RVD vs. RVD in

Newly Diagnosed Multiple Myeloma

Randomized 1:1

Transplant-eligible adults with Newly Diagnosed MM, with good performance status and kidney fxn (N = 207)

Induction: Cycles 1-4

Dara-RVD in 21-day cycles (n = 104)

Consolidation: Cycles 5-6†

Maintenance: Cycles 7-32

Dara-RVD in 21-day cycles

D: 16 mg/kg IV D1

VRd: as in induction

Dara-R in 28-day cycles

D: as in consolidation Q4W or Q8W

R: 10 mg PO D1-21 of C7-9 and 15 mg

PO D1-21 of C10

RVD in 21-day cycles (n = 103)

RVD in 21-day cycles

VRd: as in induction

R in 28-day cycles

R: 10 mg PO D1-21 of C7-9 and 15 mg PO D1-21 of C10

 Primary endpoint: CR by end of consolidation

GRIFFIN Randomized Phase II: Dara-RVD vs. RVD in

Diagnosed Multiple

reduction in progression or death

These data support use of D RVd induction/consolidation and D R maintenance as a NEW standard of care in Newly Diagnosed Myeloma

Where We Are Going…4-Drug Induction for Newly Diagnosed Myeloma

What are YOUR goals of therapy

What is your MM risk/ stage

What are your therapy options

What is your response to tx

Know what side effects to expect so you can report them

Who is on your care team

How to read your M-protein level IgG Kappa M-Protein

Obtain a second opinion

Ask about clinical trials

Be informed and empowered!

M-Protein

Advancements in Survival of Multiple Myeloma

• With new biology-based medication 3 and 4 drug regimens the response rates are now >98%

• We have had 32 drugs and tx indications FDA approved for myeloma 2015-2023!

• With novel therapies are used at diagnosis, survival has improved dramatically

— From 3.8 years to >8 years!

— The 10yr relative survival rate has nearly doubled since in the past 20 years

Myeloma is not curable…yet. But is survivable now!

People in the United States living or in a Remission from Multiple Myeloma

Audience Q&A with Panel

• Open the Q&A window, allowing you to ask questions to the host and panelists. They can either reply to you via text in the Q&A window or answer your question live.

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• If the host replies via the Q&A box – you will see a reply in the Q&A window.

Agenda After Break

6:35 – 7:15 PM Relapsed Therapy & Clinical Trials

David Vesole, MD, PhD, FACP - The John Theurer Cancer Center at Hackensack

University Medical Center

7:15 – 7:35 PM Life is a Canvas, You are the Artist

Kimberly Noonan, DNP, ANP-BC, AOCN - IMF Nurse Leadership Board, Dana-Farber Cancer Institute

7:35 – 8:00 PM Q&A with Panel

Relapsed Therapy and Clinical Trials

David Vesole, MD, PhD, FACP

The John Theurer Cancer Center at Hackensack University Medical Center

Treating Relapsed/Refractory Multiple Myeloma & Clinical Trials

David H. Vesole, MD, PhD, FACP

Director, Myeloma Program

MedStar Georgetown University Hospital

Professor of Medicine

Georgetown University School of Medicine

Co-Chief, Myeloma Division

Director, Myeloma Research

John Theurer Cancer Center at Hackensack UMC

Professor of Medicine

Hackensack Meridian School of Medicine

David.Vesole@hmhn.org

Genomic Heterogeneity Affects the Course of MM

• Most patients with MM have multiple distinct subclonal populations as a result of the expansion of genetically different myeloma cells; this causes intratumoral heterogeneity1

• MM is clonally heterogeneous at diagnosis and throughout treament2

• The genomic heterogeneity of MM contributes to treatment resistance and relapse3

• Wide variety of mutations found within a single patient may result in treatment resistance and refractory disease1,3,4

• Furthermore, subclones continually mutate over time, including after treatment, which may contribute to resistance and result in disease progression1,5

Evolution of Clonal Populations of Myeloma Cells4

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

Biochemical Relapse or Clinical Relapse

Timing of therapy

Biochemical

• Patients with asymptomatic rise in blood or urine M protein, free light chains, or plasma cells

initiation/escalation dependent on many factors

Requires immediate

Clinical

• Based on direct indicators of increasing disease and/or end-organ dysfunction

initiation/escalation of therapy

When should we treat relapsed disease?

• At biochemical relapse?

• When myeloma protein starts rising!

• When involved free light chain starts rising!

• At Clinical relapse?

• CRAB criteria (Anemia, kidney failure, high calcium or new bone disease)

• Extramedullary disease (myeloma growing at tumors outsides the bone)

Choosing Therapy for First or Second Relapse

Choices are broadest and guided by

Disease biology

Nature of relapse

Patient preference

Factors to consider

Prior autologous stem cell transplant

Prior therapies

Aggressiveness of relapse

Comorbidities

Psychosocial issues

Access to care

Options for Relapsed/Refractory Disease Continue to Increase

IMiDs Proteasome inhibitors

Thalomid (thalidomide)

Revlimid (lenalidomide)

Pomalyst (pomalidomide)

Kyprolis (carfilzomib)

Ninlaro (ixazomib)

Chemotherapy

anthracyclines Chemotherapy

alkylators Steroids

Novel mechanisms of action

Monoclonal antibodies

Cellular therapy

Velcade (bortezomib) Adriamycin

Cytoxan (cyclophosphamide) Dexamethasone

Doxil (liposomal doxorubicin)

Bendamustine Prednisone

Melphalan

XPOVIO (selinexor)

Empliciti (elotuzumab)

Venclexta (venetoclax)*

Farydak (Panobinostat)†

Pepaxto (melflufen)†

Darzalex (daratumumab)

Sarclisa (isatuximab)

Blenrep (belantamab mafodotin)‡

Tecvayli (teclistamab)§

*Not yet FDA-approved for patients with multiple myeloma; †Withdrawn from the US market in 2021; ‡Antibody-drug conjugate; §Bispecific antibody

Abecma (idecabtagene vicleucel)

Carvykti (ciltacabtagene autoleucel)

How does your oncologist decide what to do?

GREAT NEWS WE HAVE OPTIONS

BAD NEWS YOUR DOCTOR MAY GET CONFUSED

First Relapse

Not Refractory to Lenalidomide* Refractory to Lenalidomide*

Not refractory to CD38 moAB

Dara-refractory or Relapse while on CD38 moAB

Not refractory to CD38 moAB

Dara-refractory or Relapse while on CD38 moAB

KRd (preferred)

DRd

ERd, IRd

(Alternatives)

DKd or Isa-Kd Or

DPd or Isa-Pd

KCd or KPd

(preferred)

VCd or EPd

(Alternatives)

*Consider salvage ASCT in patients eligible for ASCT who have not had transplant before; Consider 2nd auto SCT if eligible and had >36 months response duration with maintenance to first ASCT

Combination is Better.

Key eligibility criteria

• RRMM

• ≥1 prior line of therapy

• Prior lenalidomide exposure, but not refractory

• Creatinine clearance

≥30 mL/min

DRd (n = 286)

Daratumumab 16 mg/kg IV

• Qw in Cycles 1 to 2, q2w in Cycles 3 to 6, then q4w until PD

R 25 mg PO

• Days 1 to 21 of each cycle until PD

d 40 mg PO

• 40 mg weekly until PD

Rd (n = 283)

R 25 mg PO

• Days 1 to 21 of each cycle until PD

d 40 mg PO

• 40 mg weekly until PD

Primary endpoint

• PFS

Secondary endpoints

• TTP

• OS

• ORR, VGPR, CR

• MRD

• Time to response

• Duration of response

Stratification factors

• No. of prior lines of therapy

• ISS stage at study entry

• Prior lenalidomide

Cycles: 28 days

Statistical analyses

• Primary analysis: ~177 PFS events

Pre-medication for the DRd treatment group consisted of dexamethasone 20 mg,a acetaminophen, and an antihistamine

ISS, international staging system; DRd, daratumumab/lenalidomide/dexamethasone; IV, intravenous; qw, weekly; q2w, every 2 weeks; q4w, every 4 weeks; PD, progressive disease; R, lenalidomide; PO, oral; d, dexamethasone; Rd, lenalidomide/dexamethasone; PFS, progression-free survival; TTP, time to progression; OS, overall survival; ORR, overall response rate; VGPR, very good partial response; CR, complete response; MRD, minimal residual disease. aOn daratumumab dosing days, dexamethasone 20 mg was administered as pre-medication on Day 1 and Day 2.

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

POLLUX

not reached

17.5 months

Median follow-up: 32.9 months (range, 0 - 40.0 months)

56% reduction in risk of progression/death for DRd versus Rd

HR, hazard ratio; CI, confidence interval. aExploratory analyses based on clinical cut-off date of October 23, 2017; bKaplan-Meier estimate.

updated analysis: PFS (time without relapse is much better with 3 drugs....)

Proteasome Inhibitor– and Immunomodulatory Drug–Based Regimens for Early Relapse

Currently Available Agents for One to Three Prior Lines of Therapy

Drug Formulation Approval

Velcade (bortezomib)

Kyprolis (carfilzomib)

Ninlaro (ixazomib)

Revlimid (lenalidomide)*

Pomalyst (pomalidomide)*

XPOVIO (selinexor)

• IV infusion

• SC injection

• IV infusion

• Weekly dosing

Once-weekly pill

• For relapsed/refractory myeloma

• For relapsed/refractory myeloma as a single agent, as a doublet with dexamethasone, and as a triplet with Revlimid or Darzalex plus dexamethasone

• For relapsed/refractory myeloma as a triplet with Revlimid and dexamethasone

Once-daily pill

• For relapsed/refractory myeloma in combination with dexamethasone

Once-daily pill

• For relapsed/refractory myeloma in combination with dexamethasone

Once-weekly pill

• For relapsed/refractory myeloma as a triplet with Velcade and dexamethasone

*Black box warnings: embryo-fetal toxicity; hematologic toxicity (Revlimid); venous and arterial thromboembolism

IV, intravenous; SC, subcutaneous

Proteasome Inhibitor– and Immunomodulatory Drug–Based Regimens for Early Relapse

OPTIMISMM

• Velcade-Pomalystdex (VPd) vs Vd Regimens compared

ASPIRE TOURMALINE-MM1 BOSTON

• Kyprolis-Revlimiddex (KRd) vs Rd

• Ninlaro-Rd (IRd) vs Rd

• XPOVIO-Velcade-dex (XPO-Vd) vs Vd

Median progression-free survival favored

• VPd: 11 vs 7 months

• KRd: 26 vs 17 months

• IRd: 21 vs 15 months

• XPO-Vd: 14 vs 9 months

Clinical considerations

• Consider for relapse on Revlimid

• VPd associated with more low blood counts, infections, and neuropathy than Pd

• KRd associated with more upper respiratory infections and high blood pressure than Rd

• IRd an oral regimen

• Gastrointestinal toxicities and rashes

• Lower incidence of peripheral neuropathy

• XPO-Vd associated with low platelet counts and fatigue with triplet, but less neuropathy than the Vd

Important Considerations for Use of Proteasome Inhibitors

Velcade

• Risk of peripheral neuropathy (PN; numbness, tingling, burning sensations and/or pain due to nerve damage)

Avoid in patients with severe existing PN

Reduced with subcutaneous once-weekly dosing

• High risk of shingles

− Use appropriate vaccination

• No dose adjustment for kidney issues; adjust for liver issues

Kyprolis

• Less PN than Velcade

• High risk of shingles

Use appropriate vaccination

• Monitor for heart, lung, and kidney side effects

Use with caution in older patients with cardiovascular risk factors

• High blood pressure

• No dose adjustment for kidney issues; adjust for liver issues

Ninlaro

• Less PN than Velcade

• High risk of shingles

Use appropriate vaccination

• Monitor for rashes and gastrointestinal (GI) side effects

GI effects occur early

• Needs to be taken at least 1 hour before or 2 hours after a meal

Important Considerations for Use of Immunomodulatory Drugs

Revlimid*

• Rash

Consider antihistamines

• Diarrhea

Consider bile acid sequestrants

• Risk of blood clots

• Risk of second primary malignancies

• Dose adjustment based on kidney function

Pomalyst*

• Low blood counts

• Less rash than Revlimid

• Risk of second primary malignancies

Important Considerations for Use of XPOVIO

Begin prophylactic anti-nausea medications. Consult with your doctor if nausea, vomiting, or diarrhea occur or persist.

Fatigue

Stay hydrated and active.

Report signs of bleeding right away. Report signs of fatigue or shortness of breath.

Monoclonal Antibody–Based Regimens at Relapse

Currently Available Naked Monoclonal Antibodies for One to Three Prior Lines of Therapy

Drug Formulation

Approval

Darzalex (daratumumab)

SC once a week for first 8 weeks, then every 2 weeks for 4 months, then monthly

• For relapsed/refractory myeloma as a single agent and as a triplet with Revlimid or Velcade or Kyprolis or Pomalyst plus dexamethasone

Empliciti (elotuzumab)

IV once a week for first 8 weeks, then every 2 weeks (or every 4 weeks with pom)

• For relapsed/refractory myeloma as a triplet with Revlimid or Pomalyst and dexamethasone

Sarclisa (isatuximab)

IV once a week for first 4 weeks, then every 2 weeks

• For relapsed/refractory myeloma as a triplet with Pomalyst or Kyprolis and dexamethasone

Monoclonal Antibody–Based Regimens for Early Relapse: Darzalex

POLLUX

Regimens compared

• Darzalex-Revlimiddex (DRd) vs Rd

CASTOR CANDOR APOLLO

• Darzalex-Velcade-dex (DVd) vs Vd

• Darzalex-Kyprolis-dex (DKd) vs Kd

• Darzalex-Pomalystdex (DPd) vs Pd

Median progressionfree survival favored

• DRd: 45 vs 18 months

• DVd: 17 vs 7 months

• DKd: 29 vs 15 months

• DPd: 12 vs 7 months

• Consider for relapses from Revlimid or Velcade maintenance

Clinical consider-ations

• DRd associated with more upper respiratory infections, low blood white blood cell counts, and diarrhea

• Consider for patients who are Revlimid-refractory without significant neuropathy

• DVd associated with more low blood cell counts

• Consider for younger, fit patients who are doublerefractory to Revlimid and Velcade

• DKd associated with more respiratory infections

• Sever side effects (possibly fatal) in intermediate fit patients 65 and older

• Consider in patients who are double-refractory to Revlimid and a proteasome inhibitor (Velcade, Kyprolis, Ninlaro)

• Severe low white blood cell counts

Monoclonal Antibody–Based Regimens for Early Relapse: Sarclisa and Empliciti

ELOQUENT-2

ELOQUENT-3

ICARIA-MM IKEMA

Regimens compared

• Empliciti-Revlimiddex vs Rd

• EmplicitiPomalyst-dex vs Pd

Median progressionfree survival favored

• Empliciti-Rd: 19 vs 15 months

• Empliciti-Pd: 10 vs 5 mos

• Sarclisa-Pomalyst-dex vs Pd

• Sarclisa-Kyprolis-dex vs Kd

Clinical considerations

• Consider for non-Revlimid refractory, frailer patients

• Overall survival benefit with Empliciti-Rd

• Empliciti-Rd associated with more infections

• Consider for patients refractory to Revlimid and a proteasome inhibitor (Velcade, Kyprolis, Ninlaro)

• Sarclisa-Pd: 12 vs 7 mos

• Sarclisa-Kd: 41 vs 19 mos

• Consider for patients refractory to Revlimid and a proteasome inhibitor (Velcade, Kyprolis, Ninlaro)

• Sarclisa-Pd associated with severe low white blood cell counts, more dose reductions, upper respiratory infections, and diarrhea

• Consider for patients refractory to Revlimid and Velcade

• Sarclisa-Kd associated with higher MRD negativity rates

• Sarclisa-Kd associated with severe respiratory infections

Myeloma: Second or higher relapse

Second or higher relapse

Refractory to IMiD, PI, Anti-CD38

Refractory to IMiD, PI, Anti-CD38, Alkylators, and Anti-BCMA

Existing drugs:

Combinations with Cyclophosphamide

that do not have IMiD, PI, Anti CD38 (e.g., KCd)

Anti BCMA strategy

Anti-BCMA

Bispecific

BCMA CAR-Ts

Elotuzumab

Selinexor

Venetoclax

Bendamustine

VDT PACE

New Drugs: Iberdomide, Mezigdomide

New bispecifics (Cevostamab, Talquetamab)

New CAR-Ts

New Monoclonals

New ADCs

Currently Available Drugs for Triple-Class

Class

Refractory

Drug

Myeloma

Formulation

Approval

Nuclear export inhibitor

XPOVIO (selinexor)

Twice-weekly pill

• For relapsed/refractory myeloma in combinatio dexamethasone (after at least 4 prior therapie disease is refractory to at least 2 PIs, at least 2 IMiDs, and an anti-CD38 mAb

Antibody-drug conjugate

Blenrep (belantamab mafodotin)*

2.5 mg/kg IV over approximately 30 minutes once every 3 weeks

• For relapsed/refractory myeloma (after at least including an anti-CD38 mAb, a PI, and an IMiD

Chimeric antigen receptor (CAR) T cell

Abecma (idecabtagene vicleucel)†

300 to 460 × 106 genetically modified autologous CAR T cells in one or more infusion bags

• For relapsed/refractory myeloma (after 4 or mo prior lines of therapy, including an IMiD, a PI, a anti-CD38 mAb

CAR T cell

Bispecific antibody

Carvykti (ciltacabtagene autoleucel)‡

0.5 to 1.0 × 106 genetically modified autologous CAR T cells/kg of body weight

Tecvayli (Teclistamab) ‡ Step up dosing then weekly SQ

IMiD, immunomodulatory agent; PI, proteasome inhibitor; mAb, monoclonal antibody

• For relapsed/refractory myeloma (after 4 or mo prior lines of therapy, including a PI, an IMiD, a anti-CD38 mAb

For relapsed/refractory myeloma (after 4 or m therapy, including a PI, an IMiD, and an anti-C

†Black box warning: cytokine release syndrome; neurologic toxicities; hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS); prolonged cytopenia

‡Black box warning: cytokine release syndrome; neurologic toxicities; Parkinsonism and Guillain-Barré syndrome; hemophagocytic lymphohistiocytosis/ macrophage activation syndrome (HLH/MAS); prolonged cytopenia

Abecma and Carvykti are available only through a restricted distribution program

XPOVIO + Dexamethasone in Relapsed/Refractory Myeloma

Previous therapies to which the disease was refractory, n (%)

Additional analyses showed clinical benefit with XPOVIO regardless of patient age and kidney function.2,3

Emerging Therapies for Relapsed/Refractory Multiple Myeloma

Bispecific antibodies

• Elranatamab, talquetamab, cevostamab, 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

CAR T-Cell Therapy and Bispecific Antibodies

Autologous CAR T-Cell Therapy: Underlying Principles

Leukapheresis Manufacturing Infusion

Collect patient’s white blood cells

Isolate and activate T cells Engineer T cells with CAR gene

Tumor cell

Targeting element (eg, CD19, BCMA, CD20)

Spacer

Transmembrane domain

Expand CAR T cells Infuse same patient with CAR T cells

Activity

CD19

Viral vector with CAR DNA

CARengineered T cell

Costimulatory domain (eg, CD28 or 4-1BB)

CD3���� (essential signaling domain)

Median manufacturing time: 17-28 days

Patients undergo lymphodepleting (and possibly salvage/bridging) therapy

CAR T-Cell Therapy Patient Journey

3

Abecma and Carvykti in Relapsed and Refractory Multiple Myeloma

CR or sCR and MRD NE CR or sCR and MRD-

ORR, overall response rate; PR, partial response; VGPR, very good partial response; CR, complete response; sCR, stringent complete response; MRD, minimal residual disease; PFS, progression-free survival

KarMMa Trial. Munshi NC et al. N Engl J Med. 2021;384:705.

CARTITUDE-1 Trial. Berdeja JG et al. Lancet. 2021;398:314; Martin T et al. J Clin Oncol. June 4, 2022 [Epub ahead of print].

CAR T: Expected Toxicities

CRS ICANS

Onset 1 9 days after CAR T-cell infusion

2 9 days after CAR T-cell infusion

Duration 5 11 days 3 17 days

Symptoms

Cytokine release syndrome (CRS) Neurotoxicity (ICANS)

• Fever

• Difficulty breathing

• Dizziness

• Nausea

• Headache

• Rapid heartbeat

• Low blood pressure

Management

• Actemra (tocilizumab)

• Corticosteroids

• Supportive care

Cytopenias Infections

• 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

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

CAR-T access remain an issue

Survey of 20 centers. Responses from 17 centers.

Transplant vs CAR T Cells

Cellular therapies CAR T-cell therapy

Patient’s cells collected

Types

Patient given chemotherapy before cells are infused back into patient Yes,

When in the course of myeloma is this usually done?

Side effects of treatment

After multiple relapses As part of initial treatment

Cytokine release syndrome; confusion

*An immune cell that is the “business end” of the system, in charge of maintaining order and removing cells. †Precursor cells that give rise to many types of blood cells. We actually collect CD34+ve cells.

Fatigue, nausea, diarrhea

Bispecific and Trispecific Antibodies

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.

Examples:

• Elranatamab

• Teclistamab

• TNB-303B (ABBV-383)

• REGN5458

• Cevostamab

• Talquetamab

BCMA, GPRC5D, or FcRH5

Now Approved: Tecvayli, the First Bispecific Antibody

Drug Formulation

Approval

Tecvayli (teclistamab)*

Step-up dosing† the first week then once weekly thereafter by subcutaneous injection

• For relapsed/ refractory myeloma (after 4 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD38 mAb)

IMiD, immunomodulatory agent; PI, proteasome inhibitor; mAb, monoclonal antibody

*Black box warning: cytokine release syndrome; neurologic toxicities

†Patients are hospitalized for 48 hours after administration of all step-up doses.

Tecvayli is available only through a restricted distribution program.

Median duration of response 18.4 months

MajesTEC-1: Duration of Response

CR or better median DOR not reached (95% CI: 16.2–NE)

• Overall median DOR of 18.4 months (95% CI: 14.9–NE), and was not yet mature with data from 71 patients (68.3%) censored

• 12-month event-free rate:

• Overall:

Overall median DOR 18.4 months (95% CI: 14.9–NE)

• Patients with CR or better:

68.5% (95% CI: 57.7–77.1)

80.1% (95% CI: 67.6–88.2)

MajesTEC-1: Overall Safety Profile; watch for infections

Teclistamab was well tolerated; discontinuations and dose reductions were infrequent

• 2 patients (1.2%) discontinued due to AEs (grade 3 adenoviral pneumonia; grade 4 PML)

• 1 patient had dose reduction at cycle 21

• The most common AEs were CRS and cytopenias

• Infections occurred in 126 (76.4%) patients (grade 3/4: 44.8%)

• 123 patients (74.5%) had evidence of hypogammaglobulinemiaa

• There were 19 deaths due to AEs, including 12 COVID-19 deaths

• 5 deaths due to teclistamab-related AEs:

• COVID-19 (n=2)

• Pneumonia (n=1)

• Hepatic failure (n=1)

• PML (n=1)

Bispecific Antibodies: >20% Activity

*Based on a recent sampling

Bispecific Antibodies Clinical Trials in Multiple Myeloma future state

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

Key Points

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.

Several additional bispecific antibodies are under clinical evaluation.

Clinical Trials

Why Are Cancer Clinical Trials Important?

• Cancer affects all of us

• Each year in the U.S.A:

• More than half a million people are expected to die of cancer—more than 1,500 people a day

• 1 of 4 deaths is from cancer

• More than 1 million new cancer cases are expected to be diagnosed

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

Do Many People Participate in Cancer Clinical Trials?

Only 3 percent of U.S. adults with cancer participate in clinical trials

Steps to make an informed decision treatment decision

Clinical Trials

• Cancer clinical trials are

– Carefully controlled research studies

– Conducted by doctors to improve the care and treatment of cancer patients

• The aim of a clinical trial is to

– Study a new therapy or a new use for an already approved therapy

– Compare a new treatment with a standard treatment to find out which one works better and/or has fewer 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

Clinical trials:

A key step in drug development

Initial

development

of new drug in lab

Drug studied in lab

Food and Drug Administration approves new drug application

The drug can now be studied in people in carefully controlled clinical trials

How How do clinical trials work?

Phase I investigates for safety and side effects, dosage and best way to give treatment–includes 20 or more people

Phase II determines effectiveness and safety–typically includes fewer than 100 (may include up to 300) people

Phase III looks at effectiveness, side effects and safety in comparison with other treatments–includes 100s to 1000s of people

Phase IV gathers more information after FDA approval & drug is on market

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

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

Why Do So Few Cancer Patients

Participate in Clinical 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

Why Do So Few Cancer Patients Participate

in Clinical Trials?

Doctors might:

• Lack awareness of appropriate clinical trials

• Be unwilling to “lose control” of a person’s care

• Believe that standard therapy is best

• Be concerned that clinical trials add administrative burdens

How to Manage Myeloma Symptoms and Side Effects

Kimberly Noonan, DNP, ANP-BC, AOCN

IMF Nurse Leadership Board, DanaFarber Cancer Institute

February 1, 2023

LIFE IS A CANVAS, YOU ARE THE ARTIST

Nurse Practitioner

Dana-Farber Cancer Institute

Boston, MA

Kimberly Noonan, DNP, RN, ANP, AOCN

OBJECTIVES

COLOR WHEEL OF TREATMENT

Myeloma treatment

FRAMING YOUR CARE

Know your care team, Telehealth & Meeting Prep, & Shared Decision Making

HEALTHY LIVING

Infection and Side Effect Management

COLOR WHEEL OF TREATMENT

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

GALLERY OF GOALS

MYELOMA TREATMENT SUPPORTIVE THERAPIES

• Rapid and effective disease control

• Durable disease control

• Minimize side effects

• Allow for good quality of life

• Improved overall survival

• Prevent disease - and treatmentrelated side effects

• Optimize symptom management

• Allow for good quality of life

DISCUSS GOALS AND PRIORITIES WITH YOUR HEALTHCARE TEAM

Transplant

Eligible Patients

MANAGING MYELOMA: THE COMPONENTS

Transplant

Consolidation

Maintenance

Initial Therapy

Transplant

Ineligible patients

Consolidation/ Maintenance/ Continued therapy

Treatment of Relapsed disease

Everyone

Supportive Care

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

Physical

• Fatigue

• Constipation

• Pain

• Neuropathy

• Impaired Physical Functioning

• Sexual Dysfunction

Psychological

• Depression

• Anxiety

• Sleep Disturbance

• Decreased Cognitive Function

• Decreased Role & Social Function

Financial

• Financial burden (80%)

• Financial toxicity (43%)

SHADES OF “AUTO” STEM CELL TRANSPLANT (ASCT)

• There are no black and white answers to deciding to undergo a transplant

• Undergoing transplant is a commitment for both you and your care partner

• Understanding the process will help bring to focus elements needed to decide if/when to undergo transplant

Clinical Experience Data from Research

Patient Preference

Adapted from Philippe Moreau, ASH 2015

THE BRIGHT DARK SIDE TO STEROIDS

Steroid Side Effects

Steroid Synergy

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

Managing Steroid Side Effects

• Consistent schedule (AM vs. PM)

• Take with food

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

• Medications to prevent shingles, thrush, or other infections

Do not stop or adjust steroid doses without discussing it with your health care provider

• Irritability, mood swings, depression

• Difficulty sleeping (insomnia), fatigue

• Increased risk of infections, heart disease

• Muscle weakness, cramping

• Increase in blood pressure, water retention

• Blurred vision, cataracts

• Flushing/sweating

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

• Weight gain, hair thinning/loss, skin rashes

• Increase in blood sugar levels, diabetes

Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR, Eastern Cooperative Oncology Group (2010) Lenalidomide plus highdose dexamethasone versus lenalidomide plus low - dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an o pen - label randomised controlled trial. Lancet Oncol 11(1):29 –37.

HEALTHY LIVING FOR PEOPLE WITH MULTIPLE MYELOMA INFECTION

AND SIDE EFFECT

MANAGEMENT

BCMA TARGETED THERAPIES ARE ASSOCIATED WITH AN INCREASED RISK OF INFECTIONS

Both viral and bacterial

– Up to a 3rd of patients on clinical trials has serious infections (requiring IV antibodies or hospitalization)

Increased risk of serious COVID complications despite history of vaccination

– Antibody levels

– Tixagevimab co - packaged with cilgavimab ( EVUSHELD )

– Immediate treatment once diagnosed Nirmatrelvir with Ritonavi ( Paxlovid )

• Start as soon as possible; must begin within 5 days of when symptoms start

Multiple myeloma

Immune dysfunction

INFECTION CAN BE SERIOUS FOR PEOPLE WITH MYELOMA

7 - 10 fold increased risk of bacterial and viral infections for people with myeloma

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

General Infection Prevention Tips

Good personal hygiene (skin, oral)

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

Growth factor (Neupogen [filgrastim])

Immunizations (NO live vaccines)

care team

• Medications (antibacterial, antiviral)

HEALTHFUL LIVING STRATEGIES: PREVENTION

Manage stress

• Rest, relaxation, sleep hygiene

• Mental health / social engagement

• Complementary therapy

Maintain a healthy weight

• Nutrition

• Activity / exercise

Preventative health care

• Health screenings, vaccinations

• Prevent falls, injury, infection

• Stop smoking

• Dental care

Maintain renal health

• Myeloma management

• Hydration

• Avoid renally - toxic medications

– Dose adjust to renal function

• Diabetes management

Protect your bones

• Nutrition, Calcium + D supplement

• Weight- bearing activity / walking

• Bone strengthening agents

“ An ounce of prevention is worth a pound of cure .” Benjamin Franklin

CARE PARTNER SUPPORT

Care partner support is essential for the entire transplant and CAR T processes

• Sedated procedures; Education sessions

• Assistance with daily activities, managing medications and alerting the medical team of changes

• Continued support and assistance is often needed in the early days after returning home. Less assistance will be needed as time goes on.

Care partner can be one person or a rotation of many people.

GI SYMPTOMS: PREVENTION & MANAGEMENT

Diarrhea may be caused by medications and supplements

• Laxatives, antacids with magnesium

• Antibiotics, antidepressants, others

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

• Sugar substitutes in sugar free gum

Avoid caffeinated, carbonated, or heavily sugared beverages

Take anti- diarrheal medication

• Imodium ® , Lomotil® , or Colestid if recommended

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

• Welchol® if recommended

Constipation may be caused by

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

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

Increase fiber

• Fruits, vegetables, high fiber whole grain foods

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

Fluid intake can help with both diarrhea and constipation, and good for kidneys. Discuss GI issues with health care providers to identify causes and make adjustments to medications and supplements.

PAIN PREVENTION AND MANAGEMENT

Pain can significantly compromise quality of life

Sources of pain include bone disease, neuropathy and medical procedures

Management

• Prevent pain when possible

• Bone strengtheners to decrease fracture risk; anti viral to prevent shingles; sedation before procedures

• Interventions depends on source of pain

• Monitor serum calcium levels

• Imaging may be needed depending on type and location of pain ( eg , MRI, PET- CT)

• May include medications ( eg bone modifying agents), activity, surgical intervention, radiation therapy, etc

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

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

PERIPHERAL NEUROPATHY MANAGEMENT

Peripheral neuropathy: damage to nerves in extremities (hands, feet, or limbs)

• Numbness

• Tingling

• Prickling sensations

• Sensitivity to touch

• Burning and/or cold sensation

• Muscle weakness

Prevention / management:

• Bortezomib once - weekly or subcutaneous administration

• Massage area with cocoa butter regularly

• Supplements:

• B - complex vitamins (B1, B6, B12)

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

• Safe environment: rugs, furnishings, shoes

If PN worsens, your HCP may:

• Change your treatment

• Prescribe oral or topical pain medication

• Suggest physical therapy

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

FATIGUE, ANXIETY & DEPRESSION

All can affect quality of life and relationships

• Fatigue is the most common reported symptom (98.8%)

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

• Anxiety reported in >35%

• Depression nearly 25% Financial concerns, disease progression, end - of - life, and change in social and sexual function were highlighted sources

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

Financial burden comes from

• Medical costs

• Premiums

• Co - payments

• Travel expenses

• Medical supplies

• Prescription costs

• Loss of income

• Time off work or loss of employment

• Caregiver time off work

FINANCIAL BURDEN

Contact the Social Services department at your hospital or clinic to talk to a social worker for assistance.

Funding and assistance may be available

• Federal programs

• Pharmaceutical support

• Non - profit organizations

• Websites:

• Medicare.gov

• SSA.gov

• LLS.org

• Rxassist.org

• NeedyMeds.com

• HealthWellFoundation.org

• Company - specific website

FRAMING YOUR CARE

Know your care team, Telehealth & Meeting Prep, & Shared Decision Making

You are central to the care team

CARE TEAM COLLAGE

Be empowered

• Ask questions, learn more

• Participate in decisions

Communicate with your team

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

• Participate in support network

You and Your Caregiver(s) Support Network

Subspecialists

Myeloma Specialist

General Hem/ Onc

Provider (PCP)

Come prepared:

PREPARE FOR VISITS & CONSIDER TELEMEDICINE

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

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

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

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

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

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

Check with your healthcare team –Is telemedicine an option?

Similar planning for “in - person” appointment PLUS:

• What is the process and what technology is needed?

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

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

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

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

SHARED DECISION - MAKING

Be empowered to be part of the treatment decision - making

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

• Understand options; consider priorities

• Use reliable sources of information

• Use caution considering stories of personal experiences

• Consider your goals/values/preferences

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

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

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

• Arrive at a treatment decision together

Philippe Moreau. ASH 2015.

YOU ARE NOT ALONE

Thank you for joining us today for the February 1, 2023, International Myeloma Foundation’s Regional Community Workshop –Northeast & Southern states.

Workshop Video Replay &

Slides

As follow up to today's workshop, we will have the speaker slides and a video replay available.

These will be provided to you shortly after the workshop concludes.

Upcoming Programs:

February 15, 2023

IMF Virtual Regional Community Workshop (RCW) - Midwest Region

5:30 PM Central Time

March 4, 2023* RETURN TO IN PERSON MEETINGS

IMF In-Person Regional Community Workshop (RCW) - San Diego

8:00AM Pacific Time

March 17, 2023

IMF Patient & Family Seminar 2023 - Boca Raton

8:00AM Eastern Time

Registration for these events can be found at myeloma.org under the “EVENTS” tab:

Thank you to our sponsors!

We want to hear from you!

Feedback Survey

At the close of the meeting a feedback survey will pop up.

This will also be emailed to you shortly after the workshop.

Please take a moment to complete this survey.