IMF Virtual Regional Community Workshop (RCW) - Pacific Southwest by International Myeloma Foundation

Welcome and Announcements Kelly Cox

Director Support Groups & Senior Director Regional Community Workshops 1

Thank you to our sponsors!

IMF REGIONAL COMMUNITY WORKSHOP Saturday July 23, 2022- Agenda

10:00 AM - Welcome and Announcements Kelly Cox, Director Support Groups & Senior Director of Regional Community Workshops 10:05 AM - Myeloma 101 and Frontline Therapy Caitlin Costello, MD, University of California San Diego 10:40 AM - Q & A with Panel 10:55 AM – Meditation and Stretch Break 11:05 AM - Relapsed Therapy and Clinical Trials Amrita Krishnan, MD, City of Hope Comprehensive Cancer Center, Duarte, CA 11:45 AM - How to Manage Myeloma Symptoms and Side Effects Donna Catamero, ANP-BC, OCN, CCRC, The Mount Sinai Health System, IMF Nurse Leadership Board 12:05 PM - Q&A with Panel

Myeloma 101 and Frontline Therapy Caitlin Costello, MD, University of California San Diego 4

Multiple Myeloma 101 Caitlin Costello, MD July 23, 2022

Multiple Myeloma Today

CML, chronic myeloid leukemia; CLL, chronic lymphocytic leukemia; MM, multiple myeloma; NHL, non-Hodgkin lymphoma. Leukemia & Lymphoma Society. Facts 2014-2015. Available at: http://www.lls.org/#/resourcecenter/freeeducationmaterials/generalcancer/facts. Accessed April 6, 2015. Siegel RL et al. CA Cancer J Clin. 2016;66:7.

PROMISE Study Promisestudy.org

MM Causes and Risk Factors  Cause of change in plasma cell development is unknown  Chronic inflammation and environmental exposures may play a role

 Risk increases with age  Men 60%, Women 40%  African Americans have double the risk of developing MM

Etiology: Risk Factors for MM

•Chronic exposure to low-dose ionizing radiation (? Radon) •Occupational exposure (e.g. chemical) •Genetic factors-increase MGUS risk in families •Chronic antigenic stimulation (eg, recurrent infections and drug allergies) •Agent orange, 9/11 exposure •Ultimately, we do not know why patients develop MM

Epidemiology of Myeloma • Incidence

• 2022 cases: 34, 470 • 1.8% of cancer cases • 7.1 per 100,2000 per yr

• Mortality

• 2022 deaths: 12,640 • 2.0% of cancer deaths • 3.2 per 100,000 per yr

• Survival

• 55.6% 5-yr relative survival

Siegel. CA Cancer J Clin. 2022;72:7-33. seer.cancer.gov/statfacts/html/mulmy.html

Slide credit: ProCE.com and clinicaloptions.com

What is multiple myeloma? Multiple myeloma Normal plasma cells

Antibodies M proteins

Light chain

Light chain Heavy chains

Multiple myeloma cells

Bone Bone marrow

Clinical Presentation: Myeloma Defining Event C

Confusion, constipation

Renal Failure

Anemia

Electrolytes disturbances

Fatigue, weakness, SOB

B Rare Presentation

Hypercalcemia

Bone Disease Osteolytic lesions, fractures

 ~15% of patients

‒ Due to renal ± bone involvement

 20%-40% have an elevated creatinine ‒ Can be reversible with treatment

 ~75% of patients

‒ Due to renal and marrow involvement

 80% of patients have osteolytic lesions ‒ 58% of patients report bone pain

Infections  decreased function of IgG and T-lymphocyte function Hyperviscosity  headache, blurred vision, epistaxis, oral bleeding, confusion Neurologic disease  neuropathy, cord compression, intracranial plasmacytomas

Rajkumar. Mayo Clin Proc. 2016;91:101. Kyle. Mayo Clin Proc. 2003;78:21. Palumbo. NEJM. 2011;364:1046. Talamo. Clin Lymphoma Myeloma Leuk. 2010;10:464.

Slide credit: ProCE.com and clinicaloptions.com

Classification and Risk of Progression to Symptomatic Myeloma Malignant transformation Symptomatic

Asymptomatic No anemia or bone lesions. Normal calcium levels and kidney function.

M-Protein Level →

Possible anemia, bone lesions, high calcium levels, or reduced kidney function.

Active myeloma 5

Normal

MGUS or SMM

Remission Frontline therapy

SMM clinical trials 0

Time* MGUS, monoclonal gammopathy of undetermined significance; SMM, smoldering multiple myeloma. *Timing is variable depending on individual risk factors Kyle RA et al. Leukemia. 2010;24:1121

Biomarkers to Predict Risk of Progression • FLC ratio ≥ 100 predicts risk (P < .0001)

• Clonal plasma cells in BM predicts risk (P < .001)

FLC ratio < 100 Median TTP: 55 mos

0.4 0.2 0

6 12 18 24 30 36 42 48 54 60 66 72

Mos to Progression

% Progression to Symptomatic Myeloma

% Progression to MM

FLC ratio ≥ 100 Median TTP: 15 mos 0.6 0.8

BM plasma cells ≥ 60%

1.0

0.8

BM plasma cells < 60%

0.6 0.4 0.2 0

HR: 13.7; P < .001 0

Mos to Progression

Larsen JT, et al. Leukemia. 2013;27:941-946. Kastritis E, et al. Leukemia. 2013;27:947-953.

100

120

Know the Diagnosis

Key Items That Define the Diagnosis MGUS

Smoldering Myeloma

• M protein <3 g/dL • Clonal plasma cells in BM <10% • No myeloma-defining events

• M protein ≥3 g/dL (serum) or ≥500 mg/ 24 hrs (urine) • Clonal plasma cells in BM ≥10%–60% • No myeloma-defining events

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

10% risk of progression/year to active myeloma

*C: Calcium elevation (>11 mg/dL or >1 mg/dL higher than ULN) R: Renal insufficiency (creatinine clearance <40 mL/min or serum creatinine >2 mg/dL) A: Anemia (Hb <10 g/dL or 2 g/dL < normal) B: Bone disease (≥1 lytic lesions on skeletal radiography, CT, or PET-CT) Rajkumar SV et al. Lancet Oncol. 2014;15:e538.

Multiple Myeloma • Underlying plasma cell proliferative disorder • AND ≥1 myeloma-defining events • ≥1 CRAB* feature • Clonal plasma cells in BM ≥60% • Serum free light chain ratio ≥100 • >1 MRI focal lesion

Key Steps to Take on Your Journey Laboratory tests and diagnosis Staging and prognosis Obtain a second opinion Treatment The promise of precision medicine

Diagnostic Workup Lab tests: • Serum protein electrophoresis (SPEP) • Urine protein electrophoresis (UPEP) • Complete metabolic panel • CBC + differential • Plasma ratio of free kappa/lamba light chains • Monoclonal protein analysis • Bone marrow biopsy:

Genetic changes occur

• FISH, cytogenetics

Imaging: • Skeletal survey • MRI, CT • PET scan ± MRI, CT Ghobrial IM, et al. Blood. 2014;124:3380-3388. Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-3548. Faiman B. Clin Lymphoma Myeloma Leuk. 2014;14:436-440.

Diagnosing Myeloma: Learn Your Labs! Blood tests

CBC

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

CMP

IFE SFLC

• Measure levels of albumin, calcium, lactate dehydrogenase (LDH), blood urea nitrogen (BUN), and creatinine. Assess function of kidney, liver, and bone status and the extent of disease.

B2M

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

SPEP

• Detect the presence and level of M protein

• Identify the type of abnormal antibody proteins

• Freelite® test measures light chains (kappa or lambda)

CBC, complete blood count; CMP, complete metabolic panel; B2M; beta-2 microglobulin; SPEP, serum protein electrophoresis; IFE, immunofixation electrophoresis; SFLC, serum free light chain assay

Diagnosing Myeloma: Learn Your Labs! Urine tests

UPEP

24-hr Urine Analysis

UPEP, urine protein electrophoresis

• Detect Bence Jones proteins (otherwise known as myeloma light chains)

• Determine the presence and levels of M protein and Bence Jones protein

Monoclonal Protein—M Spike Normal SPEP

Abnormal SPEP

• Amount/type of M protein varies among patients (IgG, IgA 80% of cases) • Abnormal M protein (immunoglobulin [Ig]) loses immune function and adheres and binds to tissues

Immunofixation to Determine Type of Monoclonal Protein

IgG kappa M protein Kyle RA and Rajkumar SV. Cecil Textbook of Medicine, 22nd Edition, 2004

Lambda Light Chains

Intact Immunoglobulin

Free Light Chain

Exposed surface Hidden surface

Previously hidden surface

FLC reference range: κ 3.3 – 19.4 mg/L λ 5.7 – 26.3 mg/L κ/λ ratio 0.26 - 1.65

Types of Monoclonal Protein (M Protein) in Multiple Myeloma

Intact immunoglobulin • For example: • IgG+kappa • IgG+lambda • IgA+kappa • IgA+lambda • etc… • 80% of myeloma cases

Light chain only • Also known as Bence Jones protein • 20% of all myeloma cases • Renal failure more common in light chain multiple myeloma; creatinine >2 mg/dL in 1/3 of cases

Non-secretory • No monoclonal protein present • 3% of cases of multiple myeloma

Diagnosing Myeloma: Know Your Imaging Tests! X-ray

Assess changes in the bone structure and determine the number and size of tumors in the bone

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

MRI

CT scan

PET scan

MRI and PET/CT appear to be more sensitive (85%) than skeletal x-rays for the detection of small lytic bone lesions.

Current Role For Imaging in MM Diagnosis Monitoring Detection of lytic lesions Detection of focal lesions

Skeletal XRay

Low-dose Whole Body CT



Detection of extraosseous lesions

Whole Body MRI

    

High sensitivity; detects early bone damage; focal and diffuse lesions can be prognostic

Advantages

Low cost; widely available

Higher sensitivity; short imaging time

Disadvantages

Lower sensitivity

Limited use for diffuse Higher cost; longer or non-lytic lesions; imaging time; limited some limited availability availability

Use

Not recommended

Recommended for routine clinical practice

Zamagni. Blood. 2019;133:644.

Recommended if CT is negative; for suspected cord compression

18F-FDG

PET/CT

    

High sensitivity; 18F-FDG SUV prognostic; determine response to treatment and evaluate relapse/progression Higher cost; potentially limited availability Recommended to detect EMD Slide credit: clinicaloptions.com

Diagnosing Myeloma: Know Your Bone Marrow Tests!

Bone marrow aspiration and biopsy Jamshidi needle

Bone marrow Hip bone

Conventional cytogenetic analysis Karyotyping

Skin

Chromosome FISH (fluorescence in situ hybridization)

Myeloma cell

REVISED- International Staging System (ISS):Prognostic Groupings Better prognosis

Poorer prognosis

Stage

Criteria

Stage I

Serum β2-microglobulin < 3.5 mg/L Serum albumin ≥ 3.5 g/dL Standard risk cytogenetics Normal LDH

Stage II

Not R-ISS stage I or stage III

Stage III

Serum β2-microglobulin ≥ 5.5 mg/L and high risk cytogenetics by FISH or high LDH [t(4;14), t(14;16), 17p]

Greipp et al. J Clin Oncol. 2005;23(15):3412; Palumbo et al J Clin Onco Aug 2015l

How aggressive is my myeloma? High Risk

• High-risk genetic abnormalitiesa,b − t(4;14) − t(14;16) − t(14;20) − Del 17p − p53 mutation − Gain 1q • RISS Stage 3 • High plasma cell S-phasec • GEP: high-risk signature

Standard Riska

• All others including: − Trisomies − t(11;14)d − t(6;14)

• Double-hit myeloma: any two high-risk genetic abnormalities • Triple-hit myeloma: three or more highrisk genetic abnormalities

Currently cannot predict with great certainty all high-risk patients.

Based on the Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013 aTrisomies may ameliorate; bBy FISH or equivalent method; cCut-offs vary; dt(11;14) may be associated with plasma cell leukemia Mikhael JR et al. Mayo Clin Proc. 2013;88:360.

What do the Chromosome Tests Mean? Risk Level* (Degree of Aggressiveness) 80

High Risk

Intermediate Risk

All others including: • Hyperdiploid • t(11;14) • t(6;14)

60 Patients affected (%)

Standard Risk

• del 17p • t(14;16) • t(14;20)

FISH

GEP • High-risk signature

FISH • t(4;14)* Cytogenetic • del 13 or hypodiploid • PCLI ≥3%

4–5 Survival (years)

*Based on the Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines 2013 Mikhael JR et al. Mayo Clin Proc. 2013;88:360.

Putting the Results Together Imaging results

Blood and urine test results Genomics

Bone marrow analysis

Staging, and Prognosis

Overview of Treatment Approach MGUS

SMM Close monitoring (observation)

Close monitoring (observation)

If high risk: possible myeloma drugs (as part of a clinical trial)

If bone loss: bisphosphonates

Active myeloma Initial therapy • Myeloma drugs • High-dose chemotherapy/stem cell transplantation (option, if possible) Maintenance option Therapies for relapsed/ refractory myeloma

Bone loss: bisphosphonates + other supportive treatments

Clinical trial participation should be considered.

Myeloma Can Be Treated, but Not Cured Asymptomatic

Symptomatic

Relapsing

Refractory

M-Protein Level →

Disease may respond or become refractory at any point

Relapse

Active myeloma

Remission 1st-line therapy ← 2-3 yr →

• Progression after achieving at least minor response or progression within 60 days of most recent therapy

• Primary refractory MM

• Progression without achieving at least minor response

Relapse MGUS or indolent myeloma

• Relapsed/refractory MM (R/R MM)

• Relapsed MM 4th-line therapy

2nd- or 3rd-line therapy ← 1-2 yr → ← 1-2 yr →

4th- to 20thline therapy

← 6 mo-1 yr →

Durie. International Myeloma Foundation Concise Review. 2018. Lonial. Clin Cancer Res. 2011;17:1264.

• Progressive disease but does not fit definition of relapsed/ refractory or primary refractory

Slide credit: ProCE.com and clinicaloptions.com

Measuring Response to Therapy Tests M-Protein Reduction

Bone Marrow

Immunofluorescence

Other

Negative

<5%

Negative

<5%

Negative

Normal

>90%

<100 mg/24 hrs

>50%

>90%

Urine

Immunofixati on

sCR

Very good partial response

VGPR

Partial response

Stable response

Does not meet criteria for response or progressive disease

Progressive disease

An increase of 25% in M-protein; an increase of 10% in bone marrow plasma cells

Response Type

Abbreviati on

Blood

Complete response

Stringent complete response

Freelite

Degree (or depth) of response is usually associated with better prognosis. Some patients do well despite never achieving a complete response (CR). Kumar S, Paiva B, Anderson KC, et al. Lancet Oncol. 2016;17(8):e328-e346.

Getting to Minimal Residual Disease (MRD): New Definitions for CR Newly diagnosed

S.S. Patient

CR Stringent CR

Molecular/Flow CR ?Cure?

Disease burden 1×108

1×104 0.0

1×1012

Minimal Residual Disease (MRD)

Rawstron A C et al. JCO 2013;31:2540-2547

Key Considerations for Optimal Disease Management Laboratory and imaging tests, tissue banking, and diagnosis Staging and prognosis Obtain a second opinion Know the standard of care Consider clinical trials

Myeloma 101: Summary Multiple myeloma can have numerous effects on the body. Genomics is growing and may lead to personalized treatments. Survival improving because of new drugs and new combinations of drugs. Treatment paradigm will continue to change with the approval of additional novel agents.

Be an informed and empowered patient!

Milestones in Multiple Myeloma Drug Approvals

2015: daratumumab 2015: ixazomib 2015: elotuzumab

2022: ciltacabtagene autoleucel

2015: panobinostat 1983: aHCT

First Documented Case

1840

2012: carfilzomib

2020: belantamab

2003: bortezomib

1960

1980

1990

2000

1958: melphalan

2010 2007: doxorubicin

1962: prednisone 1986: high-dose dexamethasone

2006: lenalidomide thalidomide

Image adapted from Kyle. Blood. 2008; 111:2962. Raje. NEJM. 2019;380:1726. Li. Circulation. 2016;133:908.

2020: isatuximab

2020Present 2019: selinexor

2013: pomalidomide

2021: idecabtagene vicleucel

Slide credit: ProCE.com and clinicaloptions.com

Navigating the MM Drug Arsenal Proteasome Inhibitors

Immunomodulatory Agents

Monoclonal Antibodies

BCMA-Specific Targets

Small Molecule Inhibitors

Bortezomib (V)

Lenalidomide (R)

Daratumumab (D)

Belantamab mafodotin-blmf (Bel)

Selinexor (X)

Carfilzomib (K)

Pomalidomide (P)

Isatuximab-irfc

Idecabtagene vicleucel

Venetoclax [if t(11;14)]

(Ide-cel)

(Ven)

Ixazomib (I)

Thalidomide (T)

(Isa)

Elotuzumab (E)

Rajkumar. Am J Hematol. 2020;95:548. Su. J Hematol Onco. 2021;14:115.

Ciltacabtagene autoleucel (Cilta-cel)

Corticosteroids

Dexamethasone (d)

Prednisone Panobinostat (Pano)

(p)

Slide credit: ProCE.com and clinicaloptions.com

Factors Affecting Treatment Selection The picture can't be displayed.

The picture can't be displayed.

Patient-Related • • • • • • • •

Age/frailty Performance status Lifestyle/pt preferences Drug metabolism Compliance/adherence Caregiver support Renal insufficiency Comorbidities

Disease-Related • • • •

ISS/LDH Rate of rise Marrow burden CRAB symptoms (hypercalcemia, renal failure, anemia, bone disease) • Extramedullary • Molecular cytogenetics/ genomics

Agarwal A, et al. Clin Lymphoma Myeloma Leuk. 2017;17:69-77.

Treatment-Related • Response to prior therapy (depth/duration) • Time to relapse • Route of administration • Single agent vs combination • Adverse events/toxicity • Clinical trial availability • Costs and copays • Access to standard of care therapies 42

Drug Therapies in Multiple Myeloma  Steroids – – – –

Dexamethasone, Medrol, Prednisone May be the most important drug to treat multiple myeloma Kills multiple myeloma cells Side effects: • Weight gain, mood swings, irritability, fluid retention, skin thinning, cataracts, insomnia, muscle loss, raise blood sugars, hiccups

–

Usually given as a pulse of treatment • Dexamethasone 40 mg every week • Prednisone 100 mg for five days in a row

–

Dose needs to be adjusted for each patient

Drug Therapies in Multiple Myeloma  IMID’s –

Thalidomide (Thalomid)

• SE: Sleepiness, numbness in feet, constipation –

Lenalidomide (Revlimid)

• SE: Low blood counts, diarrhea, rash, muscle cramps –

Pomalidomide (Pomalyst)

• SE: Low blood counts, fatigue, rash –

All can increase risk for blood clots and cause birth defects if pregnant woman exposed to them

Drug Therapies in Multiple Myeloma  Proteasome Inhibitors –

Bortezomib (Velcade)

• Subcutaneous (shot in abdomen) –

Carfilzomib (Kyprolis)

• Intraveneous –

Ixazomib (Ninlaro)

• Pill given weekly

 Work by blocking protein breakdown in the cell –

Plasma cells make protein as their main function

Daratumumab (Key takeaways)  Antibody to CD38 – –

CD38 found seemingly universally on myeloma cells Humanized IgG Kappa antibody • Will be detectable on SPEP, SIEP – 0.1 – 0.2 g/dL protein spike often noted

 Single agent activity often combined with other agents  Safety – –

50% infusion reaction on 1st infusion No other usual side effects • ? Pancytopenia (mild), increased risk for infection

 Infusion time eventually 90 minutes – now a shot  My experience – – –

Well tolerated and easy to combine with other active drugs Shot version (Faspro) particularly well tolerated and without side effects Premedications can be stopped after a while

Current Treatment Approaches: Newly Diagnosed Multiple Myeloma Are you a candidate for an autologous stem cell transplant? YES

NO • Any of the regimens listed for transplant candidates, modified dose • Dara/Rd • Doublets option, particularly for patients with health/side effect concerns • Clinical trial

3–4 cycles of therapy (induction) • Triplets or Quads (Dara-) RVD, KRD • Clinical trial

High-dose chemotherapy (melphalan) and autologous transplant Consolidation/maintenance Supportive care

Types of Stem Cell Transplant Type

Source of Stem Cells

Autologous

Patient’s blood or marrow

Allogeneic

Donor blood or marrow or umbilical cord blood

Standard and Reduced-intensity

Treatment Approach with Auto transplant Induction

Remission induction with chemotherapy (Get cancer controlled)

Consolidation

Stem Cell Mobilization

Conditioning Therapy

(Use growth factors +/- chemo to get stem cells out of bone marrow)

(Kill bone marrow cells with therapy)

Stem Cell Harvest (Collect stem cells for storage)

Treatment Approach with Auto transplant Consolidation

Maintenance Next 10–14 Days Blood Cell Count Recovery Manage Side Effects

Stem Cell Rescue (Put in stored cells to regrow bone marrow)

Measure Response

Various maintenance approaches under study, for example, thalidomide (Thalomid®), Revlimid (Revlimid®) or Velcade (Velcade®)

RVd ± ASCT and Lenalidomide Maintenance to Progression for NDMM

Content of this presentation is the property of the author, licensed by ASCO. Permission required for reuse.

Does ASCT improve outcomes for NDMM patients receiving triplet induction (RVd) and lenalidomide maintenance until disease progression?

Content of this presentation is the property of the author, licensed by ASCO. Permission required for reuse.

Primary endpoint: Progression-free survival (PFS)

Content of this presentation is the property of the author, licensed by ASCO. Permission required for reuse.

MRD / PFS by MRD status

Content of this presentation is the property of the author, licensed by ASCO. Permission required for reuse.

Key secondary endpoint: Overall survival (OS)

Content of this presentation is the property of the author, licensed by ASCO. Permission required for reuse.

Randomized Phase 2 GRIFFIN Trial of D-RVd vs RVd in Transplant Eligible NDMM: Design Induction: Cycles 1-4 D-RVd

1:1 Randomization

Key eligibility criteria: • Transplanteligible NDMM • 18-70 years of age • ECOG score 0-2 • CrCl ≥30 ml/mina

90%

D: 16 mg/kg IV Days 1, 8, 15 R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2, 8, 9, 15, 16

RVd

R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2 ,8, 9, 15, 16 21-day cycles

Stem cell mobilization with G-CSF ± plerixaforb

T R A N S P L A N T

76%

Consolidation: Cycles 5-6c

Maintenance: Cycles 7-32d

D-RVd

D-R

D: 16 mg/kg IV Day 1 R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2, 8, 9, 15, 16

RVd

R: 25 mg PO Days 1-14 V: 1.3 mg/m2 SC Days 1, 4, 8, 11 d: 20 mg PO Days 1, 2, 8, 9, 15, 16 21-day cycles

D: 16 mg/kg IV Day 1 Q4W or Q8W e R: 10 mg PO Days 1-21 Cycles 7-9; 15 mg PO Days 1-21 Cycle 10+

R: 10 mg PO Days 1-21 Cycles 7-9; 15 mg PO Days 1-21 Cycle 10+ 28-day cycles

Endpoints & statistical assumptions Primary endpoint:

sCR (by end of consolidation); 1-sided alpha of 0.1 80% power to detect 15% improvement (50% vs 35%), N = 200

Secondary endpoints:

MRD (NGS 10–5), CR, ORR, ≥VGPR

• Median age ~60; ISS3 14%, High risk 15% • Lower ASCT rate in RVd arm due to early discontinuations

Voorhees P, et al. IMW 2019.

Phase 2 GRIFFIN: Responses Deepened Over Time

• Results for end of induction, ASCT, and consolidation are based on a median follow up of 13.5 mo at primary analysis • Median follow up at 24-mo-of-maintenance therapy cutoff was 38.6 months bITT

aResponse-evaluable

population; DRVd, n=100; RVd, n=97. population: DRVd, n=104; RVd, n=103; median fu for MRD neg data for all time points is 38.6 mo. Labauch JP, et al. ASH 2021. Abstract 79.

GRIFFIN: PFS in the ITT Population

• Overall survival not reached/not mature; 3-year OS: 92.6% D-RVd vs 92.2% RVd

Labauch JP, et al. ASH 2021. Abstract 79.

MAIA: Study Design

 Multicenter, open-label, randomized phase III trial Stratified by ISS (I vs II vs III), region (North America vs other), age (< vs ≥ 75 yrs)

Patients with ASCT-ineligible ND MM, ECOG PS 0-2, CrCl ≥ 30 mL/min (N = 737)

Daratumumab + Lenalidomide + Dexamethasone (n = 368) Lenalidomide + Dexamethasone (n = 369)

28-day cycles until disease progression or unacceptable toxicity

Dosing: daratumumab, 16 mg/kg IV (QW cycles 1-2, Q2W cycles 3-6, Q4W cycle 7+); lenalidomide, 25 mg QD PO on Days 1-21; dexamethasone 40 mg QW PO or IV.

 Primary endpoint: PFS  Secondary endpoints: TTP, CR/sCR, MRD by NGS (10-5), PFS2, OS, ORR, safety Kumar. ASH 2020. Abstr 2276. NCT02252172.

Slide credit: clinicaloptions.com

% Surviving Without Progression

100

MAIA: PFS

PFS Event

48-month PFS

34.4

• 12 mos

86.2

78.4

• 24 mos

76.0

61.6

• 36 mos

67.4

48.4

PFS rate, % 60%

D-Rd: NR

38%

Median PFS, mos

D-Rd

Rd: 34.4 months

Median follow-up: 47.9 mos HR: 0.54 (95% CI: 0.43-0.67); P < .0001 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63

Pts at risk, n

Months

Rd 369 333307 280 255237220 205 196179 172 155145 132 114 79 53 22 9 2 D-Rd 368 347335 320 309 300 290 276266 256 246 237 232221201 153 111 63 26 7

Kumar. ASH 2020. Abstr 2276. Reproduced with permission.

1 1

0 0

 Risk of progression or death reduced 46% with D-Rd vs Rd  PFS benefit evident across all subgroups, except among small set with reduced hepatic function ‒ Median PFS in high-risk subgroup: 45.3 mos with D-Rd vs 29.6 mos with Rd Slide credit: clinicaloptions.com

Maintenance Therapy Why in a disease we cannot routinely cure would an effective treatment be stopped when a remission is achieved?

Maintenance Lenalidomide Following High-dose Melphalan and ASCT Meta-analysis

100

of 3 Phase III Trials

7-yr OS

62%

OS (%)

After a median follow-up of 80 months, there is an estimated: • 26% reduction in risk of death • 2.5y increase in median survival

40 N = 1209

Median OS, mos (95% CI)

Lenalidomide

Control

NE (NE-NE)

86.0 (79.8-96.0)

HR (95% CI) P value

50%

0.74 (0.62-0.89) .001

Median follow-up: 80 mos 0

100

110

120

Months The risk of developing a hematologic secondary primary malignancy (SPM) post-PBSCT was higher in the lenalidomide group (HR,2.03; 95% CI 1.14-3.61)

McCarthy PL, et al. J Clin Oncol. 2017;10;35(29):3279-3289.

Summary of Frontline MM Treatment Approach Treatment Suggestions    

Goal is to maximize initial disease response (sCR, MRD[-]) Backbone agents: steroids, PIs, IMiDs ± anti-CD38 mAbs Quad >/= triplet >>doublet regimens Choosing regimens  individual patient and tumor factors, prior exposure

Tips for Transplant Patients  Every patient who is a candidate should go to aHCT  Age and renal function are not contraindications  Limit exposure to myelotoxic agents and consider harvesting cells before prolonged exposure to lenalidomide and/or daratumumab

Maintenance  Given proven PFS ± OS benefit, maintenance remains important role  Optimal duration varies (cost, toxicity, adherence, MRD status) NCCN. Clinical Practice Guidelines in Oncology. Multiple Myeloma v5.2022.

Slide credit: ProCE.com and clinicaloptions.com

Clinical Trials in the Treatment of Myeloma Phase I

Phase II

Tests safety

Tests how well treatment works

Phase III

Compares new treatment to standard treatment

Clinical trials are so important!

Together we can open the doors of knowledge, reduce fear and increase hope about evolving treatments and improved side effect management.

Thank you

Audience Q&A with Panel

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IMF REGIONAL COMMUNITY WORKSHOP – July 23, 2022 Agenda After Break

11:05 AM - Relapsed Therapy and Clinical Trials Amrita Krishnan, MD, City of Hope Comprehensive Cancer Center, Duarte, CA 11:45 AM - How to Manage Myeloma Symptoms and Side Effects Donna Catamero, ANP-BC, OCN, CCRC, The Mount Sinai Health System, IMF Nurse Leadership Board 12:05 PM - Q&A with Panel

Relapsed Therapy and Clinical Trials Amrita Krishnan, MD, City of Hope Comprehensive Cancer Center, Duarte, CA 69

Relapsed Myeloma Amrita Krishnan, M.D., F.A.C.P.

Director of the Judy and Bernard Briskin Center for Myeloma Professor of Hematology HCT City of Hope Cancer Center

Newport Beach on a hot day on Saturday, April 25, 2020, during the COVID pandemic

(Telephoto lens Photo by Mindy Schauer,

Orange County Register/SCNG)

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Newport Beach on the same day (still of aerial video from helicopter)

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Myeloma current treatment landscape 2nd Line

3rd Line

4th Line

• Selection Based on Response to Prior Therapy • Changes between PI & IMiDs classes and or next generation

Idecabtagene vicleucel (ABECMA) Ciltacabtagene autoleucel (CARVYKTI)

Backbone of major regimens: Proteasome inhibitor (PI), Immune modulatory drug (IMiD) With and without CD38 antibodies Elotuzumab (CS1 antibody) combinations Selinexor Selinexor/Bortezomib/DEX Melflufen Belantamab: BCMA antibody drug conjugate Presenter: Yi Lin, M.D.Ph.D.

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First Relapse • Treatment selection dependent on patient-, tumor-, and treatment-related factors

   

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Sequencing of drugs with different modes of action Triplet regimens are superior to doublet regimens (response rate and PFS, and in some studies also OS) (Dose-adjusted) doublet can be the best option for frail patients Reusing a drug can be considered based on prior response and treatment-free interval

In 2021: CASTOR and POLLUX are emblematic of active combinatorial regimens

POLLUX

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Dimopoulos et al, NEJM 2016;375:1319-1331.

Randomized studies with lenalidomidedexamethasone control arms N Efficacy

Carfilzomib*

Elotuzumab

Daratumumab

Ixazomib

KRd vs Rd 792

ERd vs Rd 646

DRd vs Rd 569

IRd vs Rd 722

Median follow up, mos ORR CR Median PFS, mos

Control

Min 48 mos

Control

32.9

Control 23

87.1%

66.7%

79%

66%

93%

76%

78.3%

71.5%

32%

9.3%

55%

23%

12%

16.6

14.9

17.5

14.7

PFS HR (95% CI)

0.69 (0.57–0.83)

0.71 (0.59–0.86)

Median OS, mos

48.3

OS HR (95% CI)

0.79 (0.67–0.95)

*PFS HR 0.58 @ 18 mos

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Control

40.4

39.6

0.78 (0.63–0.96)

0.44 (0.34–0.55) NR

NR NR

0.74 (0.59–0.94) NR

NR NR

Dimopoulos MA et al. N Engl J Med. 2016;375:1319; Dimopoulos MA et al. Br J Haematol. 2017;178:896; Stewart AK et al. N Engl J Med. 2015;372:142; Stewart AK et al. Blood. 2017;130: Abstract 743.; Dimopoulos M et al. J Hematol Oncol. 2018;11:49; Moreau P et al. N Engl J Med. 2016;374:1621.

Immunotherapeutic Targets in Multiple Myeloma

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Anti-Multiple Myeloma Immunotherapeutic Agent Structures Antibody Drug Conjugate

T-Cell Bispecific Antibody

T-Cell Trispecific Antibody

Designed ankyrin repeat proteins (DARPins)

Lancman, et al. ASH 2020.

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APOLLO: Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Vs Pomalidomide and Dexamethasone (Pd) Alone

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Amrita Krishnan, MD

APOLLO: Daratumumab Plus Pomalidomide and Dexamethasone (D-Pd) Vs Pomalidomide and Dexamethasone (Pd) Alone

Dimopolous et al., 2020; 136(Supplement 1): 5-6

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CANDOR: Carfilzomib, Dexamethasone, and Daratumumab Vs Carfilzomib and Dexamethasone alone

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CANDOR: Carfilzomib, Dexamethasone, and Daratumumab Vs Carfilzomib and Dexamethasone alone

Dimopoulos et al., Lancet 2020;396:186-97.

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CANDOR: Carfilzomib, Dexamethasone, and Daratumumab Vs Carfilzomib and Dexamethasone alone

Dimopoulos et al., Lancet 2020;396:186-97.

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IKEMA: Isatuximab/Carfilzomib/Dexamethasone (Isa-Kd) vs Carfilzomib/Dexamethasone (Kd) alone

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IKEMA: Isatuximab/Carfilzomib/Dexamethasone (Isa-Kd) vs Carfilzomib/Dexamethasone (Kd) alone

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ICARIA: Isatuximab/Pomalidomide/Dexamethasone (Isa-Pd) vs Pomalidomide/Dexamethasone (Pd)

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OPTIMISMM: Pomalidomide, Bortezomib, and Dexamethasone vs Bortezomib and Dexamethasone alone, in Lenalidomide-exposed patients

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OPTIMISMM: Pomalidomide, Bortezomib, and Dexamethasone vs Bortezomib and Dexamethasone alone, in Lenalidomide-exposed patients

Richardson et al. Lancet Oncol 2019; 20:781-94.

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Belantamab Mafodotin Overview Belantamab mafodotin-blmf is a BCMA-directed antibody and microtubule inhibitor conjugate, composed of 3 components1,2

Belantamab mafodotin-blmf is internalized and MMAF is released following proteolytic cleavage from the mAb Anti-BCMA, humanized IgG1 mAb that binds to BCMAexpressing MM cells MMAF, microtubule-disrupting cytotoxic agent that leads to apoptosis of BCMA-expressing MM cells

Protease-resistant, maleimidocaproyl linker that joins the MMAF to the mAb

MMAF intracellularly disrupts the microtubule network leading to cell cycle arrest and apoptosis Belantamab mafodotin-blmf binds to BCMA expressed on normal and malignant plasma cells

Belantamab mafodotin was also shown to induce tumor cell lysis via ADCC and ADCP

Tai Y-T, et al. Blood. 2014;123(20):3128–3138. 2. Farooq A, et al. Ophthalmol Ther. 2020 July 25

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BCMA Antibody Drug Conjugates Study Phase Treatment (All are IV q 3wk)

Patients Median prior lines Triple-class refractory ORR % PFS

AEs- all grade (gr3+) Keratopathy Thrombocytopenia Anemia Infusion reaction Other

DREAMM-1

DREAMM-2

DREAMM-4

DREAMM-6

MEDI2228

I/II

Belamaf dose escalation, expansion 3.4 mg/kg

Belamaf 2.5 or 3.4 mg/kg

Belamaf 2.5 or 3.4 mg/kg + pembro

Belamaf 2.5 mg/kg + bortezomib-dex

MEDI2228

n=35

n=196

n=13

n=18

n= 82

6-7

8/ 5

range 2-11

37%

100%

NR (100% exposed)

60% (38.5% if prior dara exposure)

31% / 34%

67% / 14%

78%

61% (25/41) (0.14 mg /kg)

12 months (6.8 months if prior dara)

2.9 / 4.9 months

52% (3%) 63% (35%) 28% (17%) 12% (3%)

70% (27%)/ 75% (21%) 35% (20%)/ 58% (34%) 24% (20) / 37% (25%) 21% (3%) / 16% (1%)

67% (33%) / 57% (0%)

100% (56%) 67% (61%)

0% 32% (NR)

17% (0%)

Photophobia 54% Dry eye 20% Rash (29%) Pleural eff (20%)

50% (0%) / 14% (0%)

Trudel, et al. Blood Cancer J 2019; Lonial, et al. Lancet Oncol 2019; Nooka, et al. Hematology Reports 2020;; Popat, et al. ASH 2020; Kumar, et al. ASH 2020

Phase 3 DREAMM studies recruiting: 3: Blmf vs Pd, 7: BlmfVd vs DVd, CITY OF HOPE

8: BlmfPd vs VPd

CAR-T has entered standard of care for multiple myeloma in the U.S. Feb 2022 Cilta-cel (CARVYKTI)

These are the first regulatory approved CAR-Ts that are not targeting CD19.

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Autologous BCMA CAR-T in Pivotal Trials Ciltacabtagene autoleucel (Cilta-cel, JNJ-68284528)

Idecabtagene vicleucel (Ide-cel, bb2121, Abecma)

Orvacabtagene autoleucel (Orva-cel, JCARH125)

Binding domains

VH H

VHH

4-1BB

ide-cel CAR design MND

Anti-BCMA scFv

Promoter

CD8

4-1BB

CD3ζ

Linker Tumor binding domain

FDA Approved

Signaling domains

FDA Approved

Study Discontinued. Next generation CAR-T in trial.

Lin Y et al ASH 2020. 2. Madduri et al, ASH 2020. 3. Mailankody et al, ASCO 2020.

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KARMMA-1 REGISTRATION STUDY (IDE-CEL)

• PFS increased with higher target dose & depth of response • median PFS was 12 mo at 450 × 106 CAR+ T cells • median PFS was 20 mo in patients with CR/sCR Presenter: Yi Lin, M.D.Ph.D.

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Regulatory agency approved Dose

Munshi NC et al. N Engl J Med 2021;384:705-716.

KarMMA-1 Study (Ide-cel) Long Term Follow-up • OS is not decreased for elderly, those with extramedullary or triple refractory disease. • OS is decreased with patients with R-ISS stage.

OS in high-risk patient subgroups

Anderson L et al. ASCO 2021. Abstr 8016.

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CARTITUDE-1 Registration Study (Cilta-cel)

• 3 or more prior lines of therapy • Triple class and CD38 mAb exposed

• Median 2-YR follow-up

100%

ORR: 97.9% (95/97)

80% Patients, %

• Study population

60%

82.5%

40%

≥VGPR: 94.9%

20% 0%

3.1%

12.4%

Best response =

sCR

VGP R

Martin T et al. ASH 2021, abstr 549.

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CARTITUDE-1 Registration Study (Cilta-cel)

Progression-Free Survival

100

2-year PFS: 71.0% (95% CI, 57.6–80.9) Median PFS not reached (95% CI, 25.2–NE)

Patients (%)

2-year PFS: 60.5% (95% CI, 48.5–70.4)

Median PFS not reached (95% CI, 22.8 months–NE)

2-year OS: 74.0% (95% CI, 61.9–82.7) Median OS not reached (95% CI, 27.2 months–NE)

Overall Survival

100

0 0

Patients at risk All patients 97 sCR patients 80

95 80

85 78

77 73

74 71

67 64

18 21 Months 63 61

36 35

19 19

4 4

1 1

0 0

0 Patients at risk All patients 97

All patients

18 21 Months 78

sCR patients Martin T et al. ASH 2021, abstr 549.

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BCMA CAR-T Pivotal Trials: Toxicities Ide-Cel – Phase 1 (CRB-401)1 N = 62

Ide-Cel – Phase 2 (KarMMA-1)2 N = 128

Cilta-Cel – Phase 1b/II CARTITUDE-13 N = 97

76% / 6.5%

84% / 5%

95% / 5%

Onset day median (range)

2 (1 – 19)

1 (1 – 12)

7 (1 – 12)

Duration, days median (range)

5 (1 – 32)

5 (1 – 63)

4 (1 – 97)

36% / 1.6%

18% / 3%

21% / 10%*

CRS, Any Gr / ≥ Gr 3

ICANS, Any Gr / ≥ Gr 3

Toci: 29% Drug use Steroid: 16%

Toci: 52% Steroid: 15%

Toci: 69% Steroid: 22% Anakinra: 19%

* Delayed onset movement and neurocognitive symptoms noted in 12.4%, 9.3% Gr3 or higher. Lin Y et al ASH 2020. 2. Munshi et al ASCO 2020. 3. Madduri D ASH 2020.

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CAR-T access remain an issue Median (range) 10-50 MM CAR-T infusion volume in 2021 (<5,50-100) Number of FDA approved CAR-T slots 1 (0-4) given per month Patients on wait list 20 (5-100) (FDA approved CAR-T) Duration a patient is on waiting list 6 (2-8) months Outcomes of patients on wait list FDA approved CAR-T 25% (0%-64%) CAR-T trial 25% (0-50%) non-CAR-T trial 25% (0-50%) hospice or death 25% (0%-75%)

Survey of 20 centers. Responses from 17 centers. Kourelis T et al. ASCO 2022.

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Ide-cel and Cilta-cel in Earlier Lines of Therapy 2nd Line

3rd Line

4th Line

• Selection Based on Response to Prior Therapy • Changes between PI & IMiDs classes and or next generation

US FDA Approved LoT

Idecabtagene vicleucel

(Ide-Cel, bb2121, Abecma)

Ciltacabtagene autoleucel

(JNJ68284528, Carvykti)

KarMMa-2: Ide-cel in high-risk MM, early relapse after 1L/ASCT. KarMMa-4: Ide-cel in high risk NDMM KarMMa-3: Randomized, controlled study for Idecel vs SOC triplet regimens. CARTITUDE-5: Cilta-cel in NDMM, transplant not considered CARTITUDE-4: Randomized, CARTITUDE-6: Cilta-cel vs ASCT in controlled study for Cilta-cel vs SOC randomized, controlled study triplet regimens CARTITUDE-2: Cilta-cel in multiple exploratory cohorts KarMMa-7: Ide-cel with other drug combinations

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Unanswered Questions  Is there an upper age limit  Frailty  Renal Dysfunction  CNS involvement  Concurrent amyloid  PCL

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Teclistamab: BCMA × CD3 DuoBody® Antibody  Prognosis is poor for patients who progress on available classes of therapies, with ORR ~30%, mPFS of ~3 months, and mOS between 6–11 months1 BCMA

 Teclistamab (JNJ-64007957)a is a humanized BCMA × CD3 bispecific IgG-4 antibody that redirects CD3+ T cells to BCMA-expressing myeloma cells  Teclistamab induces T cell-mediated killing of myeloma cells from heavily-treated patients and in xenograft models2-4  Updated results from an ongoing phase 1 study of teclistamab administered IV or SC in patients with RRMM (NCT03145181) are presented here5

CD3

Myeloma cell Cell Death

Teclistamab

T cell

T cell activation Cytokine secretion Cytotoxicity

Ghandi Leukemia 2019;33:2266. 2. Labrijn AF PNAS. 2013;110:5145. 3. Frerichs KA Clin Cancer Res. 2020;26:2203. 4. Pillarisetti K Blood Adv. 2020;4:4538. 5. Usmani SZ. JCO 2020:38 (Suppl) Abstract 100. BCMA, B-cell maturation antigen; IV, intravenously; mOS, median overall survival; mPFS, median progression-free survival; ORR, overall response rate; RRMM, relapsed and/or refractory multiple myeloma; SC, subcutaneously. aIncludes technology licensed from GenMab.

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101

Updated Phase 1 Results of Teclistamab, a B-cell Maturation Antigen (BCMA) × CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM) Alfred L. Garfall1, Saad Z. Usmani2, María-Victoria Mateos3, Hareth Nahi4, Niels W.C.J. van de Donk5, Jesus F. San-Miguel6, Albert Oriol7, Laura Rosinol8, Ajai Chari9, Manisha Bhutani2, Lixia Pei10, Raluca Verona10, Suzette Girgis10, Tara Stephenson10, Jenna D. Goldberg10, Arnob Banerjee10, Amrita Krishnan11 

1Abramson Cancer

Center, University of Pennsylvania, Philadelphia, PA, USA; 2Levine Cancer Institute-Atrium Health, Charlotte, NC, USA; Universitario de Salamanca, Salamanca, Spain; 4Karolinska University Hospital at Huddinge, Stockholm, Sweden; 5Amsterdam University Medical Center, Location VU University Medical Center, Amsterdam, The Netherlands; 6Clínica Universidad de Navarra, Navarra, Spain; 7Institut Català d’Oncologia and Institut Josep Carreras. Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain; 8Hospital Clínic, Barcelona, Spain; 9Mt. Sinai School of Medicine, New York, NY, USA; 10Janssen R&D, Spring House, PA, USA; 11City of Hope, Duarte, CA, USA 3Hospital Clinico

Additional information can be viewed by scanning the QR code or accessing this link: https://oncologysciencehub.com/ASH2020/bispecifics/Garfall. The QR code is intended to provide scientific information for individual reference, and the information should not be altered or reproduced in any way

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Teclistamab: Cytokine Release Syndrome

aDay

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Parameter, n (%)

Total (N=149)

IV (n=84)

SC (n=65)

Patients with CRS

82 (55)

45 (54)

37 (57)

Median time to CRS onseta (range), days

2 (1–5)

1 (1–3)

2 (1–5)

Median duration of CRS (range), days

2 (1–8)

1 (1–7)

2 (1–8)

Patients with supportive measures to treat CRSb

76 (51)

43 (51)

33 (51)

Tocilizumab

35 (23)

22 (26)

13 (20)

Steroids

19 (13)

15 (18)

4 (6)

Low flow oxygen

9 (6)

6 (7)

3 (5)

Single low-dose vasopressor

1 (1)

Maximum CRS Grade by Dose Groupsc

80%

Grade 1

60%

54% (45/84)

40%

16%

20%

38%

57% (37/65) 15%

64% (21/33) 27%

42%

37%

RP2D

 No treatment discontinuations due to CRS

 Step-up dosing to mitigate risk of severe CRS

 CRS was generally confined to step-up and first full doses

 No grade ≥3 CRS events

1 was day of most recent dose. bA patient could receive >1 supportive therapies. cGraded according to Lee et al. Blood 2014;124:188.

103

Teclistamab: Overall Response Rate ORRa for SC Cohorts

80%

73% 60%

60% 46%

40%

n=3

Median time to first confirmed response was 1 month (0.3–3) 14/20 (70%) triple-class refractory patients responded 6/8 (75%) penta-drug refractory patients responded

n=4 n=1 n=7

̶ ≥VGPR 55%

 Most active doses were 270–720 µg/kg IV and 720–3000b µg/kg SC ̶ ̶

20% n=3 0%

n=4

 At the RP2D of 1500 µg/kg SC:

n=5 n=4

80 + 240 720 µg/kg 1500 µg/kg µg/kg (n=15) (RP2D) (n=13) PR VGPR (n=22)

ORRa at these doses was 69% (47/68) ≥VGPR was 59%; ≥CR was 26% 67% (18/27) ORR in IV cohorts and 71% (29/41) ORR in SC cohorts

 Of 11 evaluable patients across all IV and SC doses so far, 8 had MRD-neg CR at 10-6 and 1 at 10-5 sensitivityc

CR, complete response; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response. aAmong response-evaluable patients who had ≥1 study treatment and ≥1 postbaseline disease evaluation; includes unconfirmed responses.b4/4 patients responded at 3000 µg/kg SC dose. cPatient with MRD-neg CR at 10-5 was indeterminate at 10-6 due to insufficient cell counts.

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Teclistamab: Duration of Response Responders at SC Doses of 80–3000 µg/kg (n=35)  Responses were durable and deepened over time  Among responders treated at the RP2D, 15/16 (94%) are alive and progression-free after mF/U of 3.9 months (1.7–7.4)  Among responders in SC cohorts, 32/35 (91%) remain on treatment with ongoing responses after mF/U of 6.5 months (1.7–14)  Among responders treated at the most active IV and SC doses, 44/47 (94%) remain on treatment with ongoing responses after mF/U of 6.5 months (1.7–14)  5/5 evaluable patients across IV and SC cohorts showed sustained MRD negativity

D/C, discontinued; mF/U, median follow-up; MR, minimal response; PD, progressive disease; SD, stable disease.

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Bispecific Antibodies- BCMAxCD3 Bispecific Antibody

Treatment Patients Median prior lines Triple-class refractory ORR at therapeutic dose

Duration of Response AEs, (All/(Gr 3+) CRS Infections Neutropenia Anemia Thrombocytopeni a Deaths Other

AMG-420

AMG-701

CC-93269

PF-06863135

REGN5458

JNJ-64007957 (Teclistamab)

TNB-383B

Continuous IV 4/6 weeks

Weekly IV

Weekly SC

Weekly IV

Weekly IV or SC

IV q3w

n=42

n= 75

n= 19

n=18

n=45

n= 84 (IV), 44 (SC)

n= 38

3.5

IMiD + PI 36% Dara 21%

68%

IMiD 84%, PI 90%, Dara 89%

NR; 22% prior BCMA-directed

93%

79%

7/10 (70%); 5 MRD(400 μg/d)

16/45 (36%)

10/12 (83%) 9 MRD – (≥ 6mg)

6/8 (75%)

60%

(215 and 260 μg/kg)

(96mg)

30/47 (64%) 6 MRD-; (IV 270 & 720 μg/kg SC 720 & 1500

12/23 (52%)

9 months

3.8 mos (14/17 ongoing)

≥ 4 months44%

NR (up to 21 months +)

38% (2%) 33% (24%) NR NR NR 4 (10%) Polyneuropathy (5%)

61% (7%) (17%) 23% 40% 20% 4 (5%) Neurotoxicity 8% (0%)

90% (5%) NR (26%) NR (53%) NR (42%) NR (21%) 1 (5%)

61% (0%) NR NR (22%) 50% (44%) 39% (28%) 3 (17%) ISR 33% (0%)

38% (0%) 47% (20%) NR NR (9%) NR 3 (7%) IRR 7% (0%)

53% (0%) NR (15%) 55% (23%) 55% (9%) 41% (NR) 4 (3%) ISR 25% (0%) IRR 5% (0%)

(3-12mg)

(≥ 5.4mg)

21% (0%) NR NR NR (16%) NR (13%) 5 (13%)

Topp, et al. Journal of Clinical Oncology 2020; Harrison, et al. ASH 2020; Costa, et al. ASH 2019; Lesokhin, et al. ASH 2020; Madduri, et al. ASH 2020; Garfall, et al. ASH 2020; Rodriguez, et al. ASH 2020 CITY OF HOPE

TALQUETAMAB GPRC5D × CD3 Bispecific Antibody • GPRC5D is a highly expressed receptor in MM, with limited expression in healthy human tissue1-2 • Talquetamab is a first-in-class antibody that binds to CD3 and GPRC5D to redirect T cells to kill MM cells2-3 • In the ongoing, phase 1, first-in-human study of talquetamab in patients with RRMM, the RP2D was identified as a QW SC dose of 400 µg/kga (MonumenTAL-1; NCT03399799)4

T-cell activation (CD25)

Cytokine release (IFN-γ, TNF-α, IL-10…) CD3 arm

Cell kill

Talquetamab JNJ-64407564 GPRC5D × CD3 antibody

GPRC5D arm

Perforin

• Here we present updated results of safety and efficacy of talquetamab at the RP2D, with additional patients and longer follow-up

Granzymes

a400 µg/kg was selected as final dosing concentration in phase 2 for operational convenience; in phase 1, 405 µg/kg was the RP2D. GPRC5D, G protein–coupled receptor family C group 5 member D; IFN, interferon; IL, interleukin; MM, multiple myeloma; QW, once weekly; RP2D, recommended phase 2 dose; RRMM, relapsed/refractory multiple myeloma; SC, subcutaneous; TNF, tumour necrosis factor. 1. Smith EL, et al. Sci Transl Med 2019;11:eaau7746. 2. Pillarisetti K, et al. Blood 2020;135:1232-43. 3. Verkleij CPM, et al. Blood Adv 2021;5:2196-215. 4. Chari A, et al. 62nd ASH Annual Meeting and Exposition 2020, Abstract 290.

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TALQUETAMAB Overall Response Rate ORRa

80 53.3%

6.7%

Patients, %

30 20 10 0

The RP2D of 405 µg/kg SC QW has been administered to 30 patients with a median follow-up of 6.3 months (range: 1.4–12.0) for responders

•

At the RP2D:

70.0%

•

2.7%

34.7%

3.3%

≥VGPR 44%

9.3% SC total (n=75) PR VGPR

6.7%

• 70.0% ORR (21/30) 50.0%

• Median time to first confirmed response was 1 month (range: 0.2–3.8)

≥VGPR 60%

• 65.2% (15/23) of triple-refractory patients responded • 83.3% (5/6) of penta-refractory patients responded

10.0% RP2D (405 µg/kg SC QW) CR (n=30) sCR

•

Of 6 evaluable patients across IV and SC cohorts, 4 had MRD-negative CR/sCR at 10-6, including 1 patient in RP2D cohort • MRD negativity was sustained 7 months post CR in 1 evaluable patient

aInvestigator assessment of evaluable patients who had ≥1 dose of talquetamab and ≥1 postbaseline disease evaluation per 2011 International Myeloma Working Group response criteria; includes unconfirmed response. CR, complete response; IV, intravenous; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; QW, once weekly; RP2D, recommended phase 2 dose; SC, subcutaneous; sCR, stringent complete response; VGPR, very good partial response.

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TALQUETAMAB Duration of Response Duration of Response at RP2D (405 µg/kg SC QW) TR TR

•

Responses were durable and deepened over time

•

At the RP2D of 405 µg/kg SC QW: • Median duration of response was not reached

TR TR

• 17/21 responders (81%) were continuing on treatment, after median follow-up of 6.3 months (range: 1.4–12.2)

TR TR TR TR TR TR TR TR TR

• Response: End of treatment status: Intrapatient dose reduction:

TR TR

7 Months

sCR CR VGPR PR On treatment as of April 18, 2021 D/C - PD D/C - Other 135

Data in IV cohorts (not shown) were more mature • Even at subtherapeutic doses, responses are ongoing at 22+ months in patients with longer follow-up

CR, complete response; D/C, discontinued; IV, intravenous; MR, minimal response; PD, progressive disease; PR, partial response; QW, once weekly; RP2D, recommended phase 2 dose; SC, subcutaneous; sCR, stringent complete response; SD, stable disease; TR, triple-class refractory; VGPR, very good partial response.

CITY OF HOPE

Cevostamab: FcRH5xCD3 bispecific antibody  Fc receptor-homolog 5 (FcRH5) Anti-CD3 Fab region

o expressed exclusively in B-cell lineage (myeloma cells > normal B cells)1

Anti-FcRH5 Fab region

o near ubiquitous expression on myeloma cells1,2

 Cevostamab bispecific antibody 1 o targets membrane-proximal domain of FcRH5 on myeloma cells and epsilon domain of CD3 on T cellsActivation

o dual binding results in T-cell directed killing of myeloma cells1

 Phase I dose-finding experience (NCT03275103)3 o promising activity in patients with heavily pre-treated RRMM

CD3

T cell

Apoptosis

FcRH5 Myeloma cell

o manageable safety, with C1 single step-up dosing providing effective CRS mitigation

Aims: (1) share updated Phase I dosing-finding results, and (2) evaluate the impact of C1 single step-up and C1 double step-up dosing on CRS C, Cycle; CRS, cytokine release syndrome; Fab, fragment antibody binding; RRMM, relapsed/refractory multiple myeloma Li et al. Cancer Cell 2017;31:383–95 Sumiyoshi et al. EHA 2021; 3. Cohen et al. ASH 2020

CITY OF HOPE

Study overview Key inclusion criteria

Cevostamab administration

•

• •

RRMM for which no established therapy is available, appropriate, or tolerable ECOG PS 0–1 Prior CAR-Ts, ADCs, and bispecific antibodies allowed

C1 single step-up escalation‡

•

Q3W intravenous infusions for 17 cycles* CRS/infusion-related reaction mitigation – C1 step-up dosing – C1–2 corticosteroid premedication†; C1–17 acetaminophen and diphenhydramine premedication Hospitalization (≥72 hours) after each C1 infusion

C1 single step-up expansion‡

C1 double step-up escalation‡ C1D1

C1D8

C1D15

N=9

0.3

3.6

160

N=5

160

N=8

0.6

3.6

N=8

3.6

132

N=7

C1D1

C1D8

0.3

3.6

N=8

3.6

N=12

3.6

1.2

3.6

N=3

3.6

N=7

1.2

3.6

N=6

3.6

N=6

3.6

N=3

0.05–3.6

0.15–10.8

N=17

C1D1

C1D8

3.6

198

3.6

N=31

C1 double step-up expansion‡ C1D1

C1D8

C1D15

0.3

3.6

160

D15 D1

N=31

D1 D1

D1 C1 21 days

C17

C1 21 days

Cut-off date: August 25, 2021; *or until progressive disease or unacceptable toxicity occurs; †corticosteroid pre-medication optional from C3 onwards; ‡all doses in mg ADC, antibody–drug conjugate; CAR-T, chimeric antigen receptor T-cell; D, Day; Q3W, once every 3 weeks

CITY OF HOPE

C17

Baseline patient and disease characteristics N (%) of patients unless stated Age in years, median (range) Male

N=161 64 (33–82) 94 (58.4)

High-risk cytogenetics*, N (%) of patients with conclusive assay result

67/95 (70.5)

1q21 gain

50/90 (55.6)

t(4;14)

13/96 (13.5)

t(14;16)

2/90 (2.2)

del(17p)

27/112 (24.1)

Extramedullary disease Time since first multiple myeloma therapy in years, median (range)

34 (21.1) 6.1 (0.3–22.8)

N (%) of patients unless stated

N=161

Number of lines of prior therapy, median (range)

6 (2–18)

Prior anti-CD38 antibody

142 (88.2)

Prior anti-BCMA

54 (33.5)

Prior CAR-T

28 (17.4)

Prior ADC

27 (16.8)

Prior bispecific antibody

13 (8.1)

Triple-class refractory†

136 (84.5)

Penta-drug refractory‡

110 (68.3)

Refractory to last prior therapy

143 (88.8)

• Most patients had heavily pre-treated and highly refractory disease. High-risk cytogenetics were common.  *includes 1q21 gain, t(4;14), t(4;14), and del(17p) chromosomal aberrations; †≥1 IMiD, ≥1 PI, and ≥1 anti-CD38 antibody; ‡≥2 IMiDs, ≥2 PIs and ≥1 anti-CD38 antibody; BCMA, B-cell maturation antigen; IMiD, immunomodulatory drug; PI, proteasome inhibitor

CITY OF HOPE

Cytokine release syndrome N=161 130 (80.7) 69 (42.9) 59 (36.6) 2 (1.2)

N (%) of patients with CRS* Grade 1 Grade 2 Grade 3

23 (14.3) 13 (8.1) 9 (5.6) 1 (0.6)

N (%) of patients with ICANS associated with CRS Grade 1 Grade 2 Grade 3 Most common ICANS symptoms associated with CRS Confusional state Aphasia

4 (2.5) 2 (1.2)

N (%) of patients with CRS leading to treatment discontinuation

*assessed using

N (%) of patients with CRS receiving CRS management with: 1; ICANS, immune effector Tocilizumab only ASTCT 2019 criteria Steroids only Tocilizumab and steroids

• CRS primarily observed in C1 • CRS onset within 24 hours of administration in 70% of patients • CRS resolved within 48 hours of onset in 85% of patients • All but one patient with ICANS associated with CRS recovered –

the patient who did not recover had disease progression soon afterwards

1 (0.8)

60 (37.3) neurotoxicity syndrome cell-associated 35 (21.7) 26 (20.0)

• C1 step-up dosing provided effective CRS mitigation. CRS was generally confined to C1 and was mostly low Grade. Lee et al. Biol Blood Marrow Transplant 2019;25:625–38

CITY OF HOPE

Response Best response rates in efficacy-evaluable patients by dose level

• Response observed at the 20mg target dose level and above (N=143 patients)

• ORR increases with target dose ORR in C1 single step-up expansion (3.6/90mg): 29.0%

–

ORR in C1 double step-up expansion (0.3/3.6/160mg): 54.8%

• Response occurs early –

median time to first response: 1.0 mo (range: 0.7–5.9)

• Response deepens over time –

median time to best response: 2.1 mo (range: 0.7–11.4)

• MRD negativity by NGS detected in 7/10 evaluable patients with ≥VGPR (<10–5)

sCR

100 80 Patients (%)

–

VGPR

ORR: 56.7%

60 40 20 0

ORR: 36.1% 1.2%

8.4% 10.8%

1.7%

≥VGPR:2 0.5%

6.7% 25.0%

15.7%

23.3%

20–90mg dose level N=83

132–198mg dose level N=60

≥VGPR:3 3.3%

• Cevostamab was efficacious in patients with heavily pre-treated RRMM. ORR increased with target dose. CR, complete response; MRD, minimal residual disease; NGS, next generation sequencing; ORR, objective response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response

CITY OF HOPE

Duration of response Median duration of response among responders in the C1 single step-up cohorts

• Median follow-up in responders

– C1 double step-up cohorts: 6.5 months (range: 4.8–21.4) • 6 patients in the C1 single-step-up cohorts continued in response for ≥6 months after cessation of treatment

1.00 Survival probability

– C1 single step-up cohorts: 14.3 months (range: 2.7–31.8)

0.75 0.50 0.25 0 0

Number at risk 37

10 16

Time, months

Median duration of response: 11.5 months (95% CI: 6.0, 18.4)

• Responses were durable. Responses were maintained after cessation of treatment.

CITY OF HOPE

Summary: Comparison of Novel Immunotherapeutic Approaches Pros

Chimeric antigen receptor T cells (CAR-T)

Bispecific antibodies

Antibody-drug conjugates

Unprecedented ORR including MRD neg in heavily pre-treated patients

Off the shelf

Impact of bridging chemo on remission duration

Toxicities require further study – infections, neurotoxicty

Deep responses Encouraging response rates One time intervention; long chemo holiday resulting in Limited severe CRS - ? Safety in 1 hour infusion every 3 weeks median PFS ~1 year frail elderly No CRS, can be given in community Can be given in community settings settings after 1st cycle Cons Manufacturing time makes impractical for patients ? Need for admissions with initial Ocular toxicity – requires close with aggressive/rapidly progressing disease doses until CRS risk low collaboration with opthamology & impact on pt quality of life Requires complex infrastructure – stem cell lab, RN/ Dosing/schedule to be ICU/ER training – thus restricted to accredited determined Thrombocytopenia centers Need for continuous treatment Need for continuous treatment until CRS ? role in frail elderly progression until progression

Low WBC and plts post CAR-T

Modest ORR and PFS in triple class/penta refractory

Cost given relapses even in MRD neg patients; mgmt. challenging especially if soon after flu/cy given impact on T cells Lancman, et al. ASH 2020. CITY OF HOPE

Conclusions  Future therapies for myeloma  New targets  High response rates

CITY OF HOPE

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How to Manage Myeloma Symptoms and Side Effects Donna Catamero, ANP-BC, OCN, CCRC, The Mount Sinai Health System, IMF Nurse Leadership Board 119

July 23, 2022

LIFE IS A CANVAS, YOU ARE THE ARTIST Donna Catamero, ANP-BC, OCN, CCRC The Mount Sinai Health System New York, New York

Patient Education Slides 2022

PATIENT-REPORTED SYMPTOMS 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

Psychological

• Fatigue

• Depression

• Constipation

• Anxiety

• Pain

• Sleep Disturbance

• Neuropathy

• Decreased Cognitive Function

• Impaired Physical Functioning • Sexual Dysfunction

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

Financial • Financial burden (80%) • Financial toxicity (43%)

• Decreased Role & Social Function

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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

Smith LC, et al. CJON.2008;12(3)suppl:37-52. Faiman B. CJON. 2016;20(4):E100-E105.

Physical

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. 122

PAIN PREVENTION AND MANAGEMENT

Physical

Pain can significantly compromise quality of life Sources of pain include bone disease, neuropathy and medical procedures Management • Prevent pain when possible • Bone strengtheners to decrease fracture risk; anti viral to prevent shingles; sedation before procedures

• Interventions depends on source of pain • May include medications, activity, surgical intervention, radiation therapy, etc • Complementary therapies (Mind-body, medication, yoga, supplements, acupuncture, etc)

Faiman B, et al. CJON. 2017;21(5)suppl:19-36.

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

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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

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

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Tariman, et al. CJON.2008;12(3)suppl:29-36.

Physical

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

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FATIGUE, ANXIETY & DEPRESSION

Physical Psychological

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. Ramsenthaler, et al. 2016. https://doi.org/10.1111/ejh.12790. Catamero D et al. CJON. 2017; 21(5)suppl:7-18.

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Financial

FINANCIAL BURDEN Financial burden comes from • Medical costs • • • •

Premiums Co-payments Travel expenses Medical supplies

• Prescription costs • Loss of income

• Time off work or loss of employment • Caregiver time off work

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

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INFECTION PREVENTION AND COVID-19 IN PEOPLE WITH MULTIPLE MYELOMA

Patient Education Slides 2021

IMPORTANT WAYS TO SLOW THE SPREAD OF COVID-19 • Get a COVID-19 vaccine (and booster) as soon as you can • Wear a mask (N95 is most protective) that covers your nose and mouth • Stay 6 feet apart from others who don’t live with you • Avoid crowds and poorly ventilated indoor spaces • Test to prevent spread to others • Wash your hands often with soap and water. Use hand sanitizer if soap and water aren’t available

CDC = Centers for Disease Control; FDA = Food and Drug Administration. CDC website. Understanding Variants. Accessed January 30, 2022. https://www.cdc.gov/coronavirus/2019-ncov/variants/understanding-variants.html

PREVENTION: AVOID BEING EXPOSED TO THE COVID VIRUS Virus spreads from person-to-person through respiratory droplets • Respiratory droplets are from coughs, sneezes, talking of an infected person beginning ~2-14 days post exposure • More droplets with louder talking, yelling, singing • Virus does not live long on surfaces

• Close contact (within 6 feet) and indoors increases risk of spread • Airflow, ventilation matters • ~25X less transmission outdoors vs indoors

• High quality masks provide a physical barrier that prevents airborne viral spread Not infected (Exposed)

• Especially important for people at increased risk • Important in situations where distancing is not possible

COVID Images: CDC

CDC = Centers for Disease Control; MIT = Massachusetts Institute of Technology MIT Medical website. COVID-19 Updates. How safe are outdoor activities? Accessed January 30, 2022. https://medical.mit.edu/covid-19-updates/2021/08/how-safe-outdoor-activities CDC website. Types of Masks and Respirators. Accessed January 30,2022, 2020.. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/types-of-masks.html CDC website. Your Guide to Masks. Accessed January 30, 2022. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/about-face-coverings.html

Infected

CDC NOW RECOMMENDS HIGH QUALITY MASKS FOR THOSE AT RISK N95

Surgical

Cloth

KN95 This Photo by Unknown Author is licensed under CC BY

This Photo by Unknown Author is licensed under CC BY

CDC website. Types of Masks and Respirators. Accessed January 30,2022, 2020.. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/types-of-masks.html CDC website. Your Guide to Masks. Accessed January 30,2022, 2020.. https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/about-face-coverings.html

TIME TO INFECTIOUS DOSE FOR SOMEONE NOT INFECTED WITH COVID-19 COVID Image: CDC

Person Infected Is Wearing COVID Images: CDC

Nothing

Cloth Mask

Surgical Mask

(10% leakage)

<15 min*

20 min

30 min

2.5 hrs

Cloth Mask

20 min

27 min

40 min

3.3

Surgical Mask

30 min

40 min

60 min

hrs

N95 Mask

2.5 hrs

3.3

Nothing

Person Not Infected Is Wearing

N95 Mask

(10% leakage)

hrs

*New research shows that 9.8 feet (3 meters) of social distancing are not enough to ensure protection from Covid-19. Even at that distance, it takes less than five minutes for an unvaccinated person standing in the breath of a person with Covid-19 to become infected with almost 100% certainty. ACGIH website. COVID-19 Fact Sheet: Workers Need Respirators. Accessed January 30, 2022. https://www.acgih.org/covid-19-fact-sheet-worker-resp/ Cornell University website. Cornell Chronicle: Better-fitting masks offer better COVID protection. Accessed January 30, 2022. https://news.cornell.edu/stories/2021/12/better-fitting-masks-offer-better-covid-protection

INFECTION CAN BE SERIOUS FOR PEOPLE WITH MYELOMA Multiple myeloma

Treatment

Immune dysfunction

General Infection Prevention Tips • Good personal hygiene (skin, oral) • Environmental control (wash hands, avoid crowds and sick people, etc)

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.

As recommended by your health care team

• Growth factor (Neupogen [filgrastim]) • Immunizations (NO live vaccines) • Medications (antibacterial, antiviral)

Brigle K, et al. Clin J Oncol Nurs. 2017;21(5)suppl:60-76. Faiman B, et al; IMF Nurse Leadership Board. Clin J Oncol Nurs. 2011;15(Suppl):66-76. Miceli TS, et al. Clin J Oncol Nursing. 2011;15(4):9-23.

ASH Website. COVID-19 Resources. Accessed January 30, 2022. https://www.hematology.org/covid-19/covid-19-and-multiple-myeloma

132

Manage stress

HEALTHFUL LIVING STRATEGIES: PREVENTION

• 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

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

• Dental care

“An ounce of prevention is worth a pound of cure.” Benjamin Franklin Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56. Brigle K, et al. CJON. 2017;21(5)suppl:60-76. Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Faiman B, et al. CJON. 2011;15suppl:66-76. Miceli TS, et al. CJON. 2011;15(4)suppl:9-23.

133

HEALTHFUL LIVING STRATEGIES: KEEP ACTIVE Do Keep a log or journal of your activity • Notify your healthcare provider about sudden onset of pain, progressive weakness, headaches, blurred vision, numbness, and tingling •

•

Dehydration can lead to low blood pressure, falls

Movement therapies can reduce stress, promote sleep Yoga, Pilates, Tai Chi Shown to improve sleep and sleep quality, • Improved quality of life & mood •

Do Not: Overdo it • Force exercise • Try things without discussing with provider • Consider weight lifting limits •

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

Boullosa DA, et al., Jul 2013;45(7):1223-1228. Faiman B et al., Clinical Journal of Oncology Nursing. 2008;12(0):53-62; Rome S et al., Clin J Oncol Nurs. Aug 2011;15 Suppl:41-52. Miceli T et al., Clinical Journal of Oncology Nursing. 2011;15:9-23; Coleman EA et al.,Oncol Nurs Forum. May 2008;35(3):E53-61.

134

Stress during an infectious disease outbreak may sometimes cause the following: • Fear and worry about your own • • • • • •

health and the health of your loved ones Fear/worry about your financial situation or job, or loss of support services you rely on Changes in sleep or eating patterns Difficulty sleeping or concentrating Worsening of chronic health problems Worsening of mental health conditions Increased use of tobacco, and/or alcohol and other substances

CDC = Centers for Disease Control; COVID-19 = coronavirus 2019. CDC website. How to Select, Wear, and Clean Your Mask. Accessed October 27, 2020.

MANAGING STRESS DURING A PANDEMIC Take care of your Mental Health

• •

Take breaks from watching, reading, or listening to news stories Take care of your body

– Take deep breaths, stretch, – – – –

• •

or meditate Try to eat healthy, well-balanced meals Exercise regularly Get plenty of sleep Avoid excessive alcohol and drug use

Make time to unwind Connect with others. While social distancing measures are in place, consider connecting online, through social media, or by phone or mail

PREPARE FOR VISITS & CONSIDER TELEMEDICINE Come prepared: • Bring a list of current medications, prescribed and • • •

• •

over the counter Write down your questions and concerns. Prioritize them including financial issues Have there been any medical or life changes since your last visit? Current symptoms - how have they changed (improved, worsened, stable)? Keep a symptom diary. Bring it along Communicate effectively: your health care team can’t help if they don’t know Know the “next steps”, future appointments, medication changes, refills, etc

IMF Telemedicine Tip Sheet. In development.

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

Data From Research

HCP Clinical Experience TREATMENT DECISION

Your Preference Philippe Moreau. ASH 2015. 137

KNOWLEDGE IS POWER USE REPUTABLE SOURCES Website: http://myeloma.org

IMF TV Teleconferences

eNewsletter: Myeloma Minute

Download or order at myeloma.org

IMF InfoLine 1-800-452-CURE 9am to 4pm PST 138

CLINICAL TRIALS: EARLY ACCESS TO PROMISING TREATMENTS Preclinical PHASE 1

PHASE 2

ANIMAL STUDIES FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS

• • •

Determine metabolism and PK/PD actions, MTD, and DLT Identify AEs Gain early evidence of effectiveness, studied in many conditions; typically, 20 to 80 patients; everyone gets agent

EVALUATION OF EFFECTIVENESS IN A CERTAIN TUMOR TYPE

• •

Determine short-term AEs and risks; closely monitored Includes up to 100 patients, typically

PHASE 3

GATHER ADDITIONAL EFFECTIVENESS AND SAFETY INFORMATION COMPARED TO STANDARD OF CARE

PHASE 4

APPROVED AGENTS IN NEW POPULATIONS OR NEW DOSE FORMS

• •

Placebo may be involved if no standard of care exists; 100s to several thousand patients Often multiple institutions; single or double blind

AE = adverse event; DLT = dose-limiting toxicity; MTD = maximum tolerated dose; PD = pharmacodynamics; PK = pharmacokinetics. Faiman B, et al. Adv Pract Oncol. 2016;7:17-29.

139

HOW TO FIND CLINICAL TRIALS

Clinicaltrials.gov https://clinicaltrials.gov/

IMF Infoline US & Canada 800-452 CURE (2873) Worldwide: 1-818-487-7455 infoline@myeloma.org

140

CLINICAL TRIAL MYTHS: DISPELLING INACCURACIES MYTH: If I participate in a clinical trial, I might get a placebo, not active treatment MYTH: If I participate in a clinical trial, I can’t change my mind

• Phase 1 and 2, everyone gets active treatment • Phase 3 standard of care vs new regimen: often standard regimen with/without additional agent in MM trials • Patients can withdraw their consent for clinical trial participation at any time

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

• Mention the option and give the patient the opportunity; implicit and explicit biases can limit participation • Some groups may need more information about clinical trials to feel comfortable with participation

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

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

MYTH: Clinical trials are expensive and not covered by insurance

• Research costs are typically covered by the sponsoring company • Standard patient care costs are typically covered by insurance • Check with clinical trial team/insurers; costs such as transportation, hotel may not be reimbursed and are paid by patient

MM = multiple myeloma.

PhRMA website. Accessed April 15, 2022. https://phrma.org/-/media/Project/PhRMA/PhRMA-Org/PhRMA-Org/PDF/A-C/CLINICAL-TRIALS-MYTH-FACTPRINT.pdf?hsCtaTracking=f6689b95-1626-40d9-8c87-c6b8d31600a4%7C35221aa8-d487-4db3-9416-b9c3c35e3bac.

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IMPORTANCE OF DIVERSITY IN CLINICAL TRIALS “[P]eople from racial and ethnic minority and other diverse groups are underrepresented in clinical research. This is a concern because people of different ages, races, and ethnicities may react differently to certain medical products.” –FDA

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

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YOU ARE NOT ALONE

Thank you to our sponsors!

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