M-power Baltimore Community Workshop by International Myeloma Foundation

Welcome and Speaker Introductions Kelly Cox IMF Director, Support Groups and Senior Director, Regional Community Workshops

Today’s Presenters

Dr. Joseph Mikhael Chief Medical Officer International Myeloma Foundation

Dr. Ashraf Badros University of Maryland Baltimore, MD

Amy E. Pierre RN,MSN,ANP-BC Memorial Sloan Kettering Cancer Center Montvale, NJ

Bonnie Downing, MS Patient Advocate Baltimore, MD

AGENDA Welcome and Speaker Introductions

Kelly Cox

Race Matters in Myeloma Care & Survival

Dr. Mikhael

Myeloma for Patients Just Getting Started

Dr. Mikhael

When Myeloma Comes Back

Dr. Badros

Audience Questions

Panel

Break

AFTER BREAK Changing the Course of Myeloma

Dr. Mikhael

Changing the Course of Myeloma in Maryland

Dr. Badros

Making Room for Hope and Joy

Bonne Downing

How to Manage Symptoms and Side Effects

Amy Pierre

Audience Survey and Questions

Panel

Wrap up and thanks

Kelly Cox

Race Matters in Myeloma Care and Survival

Important about Myeloma andcancer African Americans 1. Myeloma is Facts the most common hematologic in African Americans Currently, African Americans comprise 14% of the total population of the USA and nearly 20% of myeloma patients…

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

Important Facts about Myeloma and African Americans 2. MGUS and Myeloma is TWICE as common in African Americans

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

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

Important Facts about Myeloma and African Americans 3. African Americans are younger at diagnosis by about 5 years

Median Age at Diagnosis With MM Is Approximately 5 Years Earlier for Black vs Whites Hispanics1

African Americans1

Asians1

Whites1

YEARS

The median age at diagnosis for all patients is 69 years MM = multiple myeloma.

Ailawadhi S, et al. Br J Haematol. 2012;158:91-98. National Cancer Institute. SEER Stat Fact Sheets: Myeloma. Surveillance, Epidemiology, and End Results Program website. Accessed February 11, 2021. http://seer.cancer.gov/statfacts/html/mulmy.html.

Important Facts about Myeloma African Americans 4. Survival improvements in myeloma haveand not been as pronounced in African Americans

Important Facts about Myeloma and African Americans 5. There is a longer time to diagnosis from the onset of symptoms Studies have shown the delay in diagnosis is on average 6 months LONGER in African Americans

Ailawadhi et al. Racial disparities in treatment patterns and outcomes among patients with multiple myeloma: a SEER-Medicare analysis Blood Adv 2019; 3(20): 2986-94

Important Facts about andTRIPLET African Americans 6. Africans Americans are lessMyeloma likely to receive therapies

1. NecampJ, et al. Blood. 2016;128:4502. 2. Chehab S, et al. Cancer. 2018;124(8):4358-43651

Important Facts about and African Americans 7. African Americans are less Myeloma likely to receive Stem Cell Transplants

8. Although African comprise nearly of all Americans MM patients, Important FactsAmericans about Myeloma and 20% African they only represent 8% of patients on clinical trials

9. There are biologic in African and Americans withAmericans MM that Important Facts differences about Myeloma African may lead to lower risk disease African ancestry associated with less aggressive disease Higher prevalence of [a]: t(11;14) t(14;16) OS by Race and t(11;14)[b] t(14;20)

Lower prevalence[c]: 13q deletion 17p deletion •

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

a. Baughn LB, et al. Blood Cancer J. 2018;8:96; b. Badar T, et al. Cancer. 2020;127:82-92; c. Kazandjian D, et al. Blood Cancer J. 2019;9:15; d. Munjuluri A, et al. Blood. 2019;134:4388. 16

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

So what can we do about this? • It is a complex problem and requires a complex solution • Key themes of Success: • Awareness, Education, Advocacy and Empowerment in the lay community • Education, Cultural Competence, Access in the medical community • Policy, Expectations, Commitment in the regulatory and corporate community

• This is impossible without genuine collaboration between ALL stakeholders

The International Myeloma Foundation African American Initiative ⚫

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

❑ Increase awareness

❑ Increase education ❑ Increase support

❑ Increase research 19 19

Myeloma for Patients Who Are Just Getting Started M-Power Baltimore September 2021 Joseph Mikhael, MD, MEd, FRCPC Chief Medical Officer, International Myeloma Foundation Professor, Translational Genomics Research Institute (TGen) City of Hope Cancer Center

The Basics of Blood • •

The blood is an “organ” made up of both cells and liquid “plasma” Think of wine (red/white/rose)

1. Red Cells – carry Oxygen…trucks 2. White Cells – immune system…army 3. Platelets – help with clotting…ambulance

All produced in the blood factory = Bone Marrow

What is Cancer? • Simple definition:

– Identical, uncontrolled growth

• The body usually has a balance to allow cells to grow in the right place for the right period of time – When that system is unbalanced, cancers grow – Ie, solid tissue (breast, colon…) or blood cells

• The “double whammy” of blood cancers is that they are the cells meant to protect you

What is Multiple Myeloma? Multiple Myeloma* is a blood cancer that starts in plasma cells of the spongy center of bones (bone marrow). – This is where stem cells mature into red blood cells, white blood cells, and platelets. – Myeloma cells are abnormal plasma cells that make an abnormal antibody called “M protein”. * Myeloma is NOT a bone cancer or skin cancer (melanoma), it is a type of blood cancer.

Multiple Myeloma Snapshot National MM Statistics 34,920 Estimated New Cases in 2021

12,410 Estimated Deaths in 2021

Trends in MM Natural History by Race MM Incidence

➢

MM ➢ Mortality

The Average Survival of patients with myeloma is IMPROVING! The expected survival is nearly 10 years for all patients, but still less than 5 years in patients with high risk disease

➢ MM Survival

Higher incidence in AA vs White patients: • 15.9 vs 7.5 cases per 100,000 per year Higher mortality in AA vs White patients: • 5.6 vs 2.4 MM deaths per 100,000

5-year relative survival evolution from 1973 to 2005 • Survival for White patients increased significantly from 26.3% to 35% • Survival for AA patients increased from 31% to 34.1%

Myeloma Is a Cancer of Plasma Cells • • •

Cancer of plasma cells Healthy plasma cells produce immunoglobulins G, A, M, D, and E Myeloma cells produce abnormal immunoglobulin “paraprotein” or monoclonal protein

FAST STATS

1.8% of all cancers; 17% of hematologic malignancies in the United States Most frequently diagnosed in ages 65 to 74 years (median, 69 years)

Bone marrow of patient with multiple myeloma

The average age of diagnosis of 4-5 years younger in African American and Hispanic patients

Image courtesy of American Society of Hematology Kyle et al. Mayo Clin Proc. 2003;78:21-33;

Multiple Myeloma diagnosis can be challenging

Fatigue

Bone Pain Kyle RA. Mayo Clin Proc. 2003;78:21-33.

Anemia

Multiple Myeloma Typically Preceded by Premalignant Conditions Premalignant MGUS1-4

Malignant SMM1-5,8

(Monoclonal Gammopathy of Undetermined Significance)

(Smoldering Multiple Myeloma)

Active Multiple Myeloma6-8

Clonal plasma cells in bone marrow

<10%

10%-60%

>10%

Presence of Myeloma Defining Events

None

Yes

~1% per year

~10% per year

Not Applicable

No; observation

Yes for high risk*; No for others

Yes

Condition

Likelihood of progression Treatment

* In clinical trial (preferred)

or offer treatment for those likely to progress within 2 years

1. Kyle RA, et al. N Engl J Med. 2007;356:2582-90. 2. International Myeloma Working Group. Br J Haematol. 2003;121:749-57. 3. Jagannath S, et al. Clin Lymphoma Myeloma Leuk. 2010;10(1):28-43.

4. Kyle RA, et al. Curr Hematol Malig Rep. 2010;5(2):6269. 5. Mateos M-V, et al. Blood. 2009;114:Abstract 614. 6. Durie BG, Salmon SE. Cancer. 1975;36:842-854.

7. Durie BG, et al. Leukemia. 2006;20(9):1467-1473. 8. Rajkumar SV, et al. Lancet Oncology 2014; 15:e538e548.

2014 IMWG Active Myeloma Criteria: Myeloma-Defining Events Clonal bone marrow ≥10% or bony/extramedullary plasmacytoma AND any one or more Myeloma-Defining Events

Calcium elevation R enal complications A nemia B one disease

Clonal bone marrow ≥60%

FLC

sFLC ratio >100

MRI

>1 focal lesion by MRI

BM, bone marrow; FLC, free light chain; MRI, magnetic resonance imaging; sFLC, serum free light chain. Rajkumar et al. Lancet Oncol. 2014;15:e538-e548. Kyle et al. Leukemia 2010;24:1121-1127.

More About the Common “CRAB” Symptoms Low Blood Counts • May lead to anemia and infection • Anemia is present in 60% at diagnosis 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)

Weakness Fatigue Infection

Weakness Bone pain Loss of Appetite & Weight loss

About 10% to 20% of patients with newly diagnosed myeloma will not have any symptoms. 29

How to Choose a Treatment Plan

Age

Lifestyle Goals of Therapy

Patient Preference

Myeloma Symptoms

Second/Expert Opinion • You have the right to get a second opinion. Insurance providers may require second opinions.

• A second opinion can help you: – Confirm your diagnosis

– Give you more information about options – Talk to other experts – Introduce you to clinical trials – Help you learn which health care team you’d like to work with, and which facility 31

Tools of the Trade for Frontline Therapy Standard Drug Overview

Class

Drug Name

IMiD immunomodulatory drug

Revlimid (lenalidomide)

R or Rev

Thalomid (thalidomide)

T or Thal

Chemotherapy Steroids Monoclonal Antibodies

V or Vel or B

Administration Oral

Kyprolis (carfilzomib)

C or K or Car

Intravenous (IV) or subcutaneous injection (under the skin)

Ninlaro (ixazomib)

N or I

Oral

Cytoxan (cyclophosphamide)

Alkeran or Evomela (melphalan)

M or Mel

Decadron (dexamethasone)

Dex or D or d

Prednisone

Daratumumab (Darzalex)

Dara

Velcade (bortezomib) Proteasome inhibitor

Abbreviation

Oral or intravenous Oral or intravenous Intravenous (IV)

Pillars of Myeloma Treatments • Doxorubicin, Panobinostat, Steroids

Belantamab mafodotin

• Others?

New Immune Drugs Proteasome Inhibitors

Immunomodulatory

Bortezomib Carfilzomib Ixazomib

Thalidomide Lenalidomide Pomalidomide

Monoclonal Antibodies Daratumumab Elotuzumab Isatuximab

Alkylators

• Steroids • Elotuzumab

Selinexor

Melphalan, Cyclophosphamide • Other Melflufen Conventional

CAR T Cell Therapy?

Chemo (Bendamustine, DPACE…) 33

General Principles of Initial Therapy 1. 2. 3. 4. 5.

Frontline therapy has a significant impact on long term survival We don’t “save the best for last” but use the best we have early on We leverage combinations of drugs to best control the myeloma We seek a DEEP and DURABLE response We mix and match from the 3 major classes of drugs and add steroids: Proteasome Inhibitors Immunomodulatory Drugs Monoclonal Antibodies 6. We decide early on whether or not someone will have a stem cell transplant

Personalized Approach to Frontline Therapy Newly Diagnosed MM and Risk Stratified

Factors to be considered for ASCT Age, performance status (PS), comorbidities (R-MCI score, HCT-Cl) and organ function

ASCT Eligible

ASCT Ineligible

Treatment Algorithm in Frontline Newly Diagnosed MM

Not Transplant Candidate

Transplant Candidate VRd x 4 cycles

VRd x 8-12 cycles followed by Len

DRd

Early Auto SCT followed by Maintenance

Collect & store Continue VRd x4 Maintenance Delayed Transplant

*Based on CALGB 100104, S0777, IFM-2009, MAIA ¶ VTd/VCd if VRd not available RAJKUMAR SV. 2020 36

Transplant Eligible Key Questions:

1. Is Transplant still necessary?

2. What is the triplet combination? (VRD or KRD)

3. Should we switch to quadruplet combinations? (D-VRD, D-KRD or I-VRD, I-KRD)

Transplant Eligible Key Questions:

1. Is Transplant still necessary? YES, it seems that it still helps with DEPTH and DURATION of response 2. What is the triplet combination? (VRD or KRD) Both are legitimate, we tend to use VRD more but KRD in certain patients 3. Should we switch to quadruplet combinations? (D-VRD, D-KRD or I-VRD, I-KRD) It is still early, but is clearly promising and will come soon…

Frontline Therapy and Transplant - Conclusions

• We will likely be transitioning to quadruplets in frontline eligible patients in the near future • Transplant still has a role in MM even with long term use of novel agents • It is still unclear if we should routinely give consolidation therapy after transplant • We can likely improve on current maintenance strategies of lenalidomide alone by adding daratumumab or carfilzomib

Transplant Ineligible Key Questions: 1. Are triplets better than Doublets? (VRD vs RD and DRD vs RD)

2. How long should patients be treated?

3. How can we make these combinations more tolerable?

Transplant Ineligible Key Questions: 1. Are triplets better than Doublets? (VRD vs RD and DRD vs RD) YES, this has been a consistent trend, but it has to be matched to the patient as some may still receive a doublet 2. How long should patients be treated? In general, the longer the better – but hopefully we will develop stopping rules in the future

3. How can we make these combinations more tolerable? Using drugs that impair quality life LESS is critical… 41

Conclusions in Transplant Ineligible Patients • There is more overlap than ever between therapies for transplant eligible and transplant ineligible patients • Although ASCT remains the standard of care, use is likely to decline in patients who are 65-75 or with significant comorbidities

• Continuous therapy has resulted in better outcomes • The balance of toxicity and efficacy is particularly important in this population • My approach is to select 2 agents from the 3 Novel Classes (PIs, IMiDs and MoAbs) – I favor DRD in standard risk patients – I favor VRD in high risk patients

• DRD is more easily delivered and feasible • D-VRD may well be a future standard of care 42

The Evolution of Myeloma Therapy VD Rev/Dex CyBorD

Now

VTD VRD KRD D-VMP DRD

Nothing Thalidomide? Bortezomib SCT Tandem ASCT (?)

Front line treatment

Induction

New

D-VRD Isa-VRD D-KRD Isa-VRD

Ixazomib Lenalidomide Combinations

Maintenance

Bortezomib Panobinostat Lenalidomide Daratumumab Ixazomib Carfilzomib Pomalidomide Elotuzumab Isatuximab Selinexor Belantamab mafodotin Melphalan flufenamide Relapsed

Consolidation

Post consolidation

Rescue

“more” induction

Daratumumab? Lenalidomide + PI

CAR T Cell Therapy Bispecific/Trispecific Antibodies Cell Modifying Agents Venetoclax? PD/PDL-1 Inhibition Multiple small molecules ++++++++

THANK YOU! Joseph Mikhael, MD, MEd, FRCPC Chief Medical Officer, International Myeloma Foundation Professor, Translational Genomics Research Institute (TGen) City of Hope Cancer Center Director of Myeloma Research and Consultant Hematologist, HonorHealth Research Institute jmikhael@myeloma.org

Relapsed/Refractory Multiple Myeloma

Ashraf Badros, MB; ChB Professor Of Medicine Director of Multiple Myeloma Service Greenbaum Comprehensive Cancer Center University of Maryland

RRMM

• Median Overall Survival is improving •

3 yrs in 1990s; now 8-10 yrs

• 15-20% are cured “?definition” •

Multiple Myeloma Today

Chronic disease or off therapy

• Unmet need still exist •

High-risk disease

•

Understand disparity in different populations (biology, response to therapy, etc..

•

Management of therapy side effects

• Optimal use of current therapies upfront and sequence at relapse is evolving

Melphalan Corticosteroids 1958 1962

Auto SCT 1983

Carfilzomib

Thalidomide 1999 Bortezomib Lenalidomide 2002

2012

Pomalidomide 2003

Selinexor 2019

Panabinostat Ixuzumib Daratumumab Elotuzumab 2015

Melflufen Abecma 2021

Isatuximab Belantamab 2020

Definitions: Relapse - Asymptomatic

- Symptomatic

Disease coming back after a response to therapy Biochemical (number progression) • ≥25% increase of (M-protein) in the serum (≥0.5 g/dL) or in the urine (≥200 mg/d) • ≥25% increase involved and uninvolved serum-free light chains (>10 mg/dL) • ≥10% increase of bone marrow plasma cells • New soft tissue plasmacytomas or bone lesions or ≥50% (and ≥1 cm) increase in size Clinical • End organ dysfunction such as hypercalcemia, renal failure, anemia, and bone lesion/fractures

Patients who achieve a response, and then either become non-responsive while receiving therapy or who progress within 60 days after stopping therapy (RRMM)

Relapse & Refractory

Serum & Urine protein electrophoresis and immunofixation Serum-free light chain Serum beta-2-macroglobulin

Diagnostic Procedures for RRMM

Chemistry: Calcium, Creatinine, serum lactate dehydrogenase CBC and peripheral blood smear (?circulating plasma cells) Bone marrow: fluorescent in situ hybridization (FISH) Skeletal Lesion or extramedullary plasmacytoma (MRI or PET)

Challenges in RRMM therapy

Disease Tempo Change in biology

• Asymptomatic Observation • Low risk

Urgent Therapy

• High risk (del 17p • Symptomatic

Challenges in RRMM therapy

Who is relapsing Patient Factors

Age Reserve

• Is not an obstacle for any therapy • Comorbidity is …

• Natural aging • Frailty • Support (driving, caregiver, etc..

Challenges in RRMM therapy

Prior Therapy

What/When

Side Effects

• Refractory Triple Class refractory? • Exposed Duration of response

• Heart disease • DM • PN • Kidney disease

Challenges in RRMM therapy

Prior Therapy

What/When

Side Effects

• Refractory Triple Class refractory? • Exposed Duration of response

• Heart disease • DM • PN • Kidney disease

Challenges in RRMM therapy

Cure? Goals of Therapy

Prevention of Damage

• Deep response (MRD?) • Symptom relief

• Bone disease • PN • Infection

Quality of Life is a crucial part of any decision How much time will I get from this therapy? & How much my QoL is impacted?

NDMM R High risk VRD + Elo x 8

Maint VRD + Elo

SWOG: NCT01668719

3-4 Drug regimen Response Rates of Different Induction Regimens

If eligible 1-Auto-SCT

Maintenance IFM 2009 – RVD vs. Autotransplant Maintenance-lenalidomide

RVD +/- SCT

Newly Diagnosed Patients Today

Meta-analysis

N=3 50

Mailankody S et al. Nat. Rev. Clin. Oncol. 2015;12:286-95

RVD CRD +/Daratumumab

PFS 50 m vs. 36 m CR 59% vs. 48%

MRD Status and OS

McCarthy P; at al. JCO 2017, 35, 3279-3289. BMT CTN0702 STaMINA Trial Attal M et al. N Engl J Med 2017

An option in selected transplant-eligible patients • Available stem cells have been collected • Remission > 18-24 months after the first auto-SCT

Second Auto-SCT

• Phase III German trial comparing re-induction Rd followed by salvage autoSCT Vs Rd did not prove the efficacy of auto-SCT in terms of ORR, PFS, and OS;

I believe there is no role for salvage auto-SCT in the era of triplet combinations in the RRMM setting. If cells are stored we usually use them to correct cytopenia before next therapy or clinical trial.

Gol dschmidt H, et al. Blood (ASH Abstracts) 2018;132(Suppl):253.

An option with reduced induced conditioning in young and fit patients who have high-risk cytogenetics “newly diagnosed” “on clinical trial”

Allogeneic SCT

• The largest outcome series, from European Blood and Marrow Transplantation data, reported a 3-year PFS of 41% and OS of 21% in heterogeneous population of RRMM • Registry-based analysis comparing salvage auto-SCT and allo-SCT RRMM patients showed no advantage for allo-SCT; however, few long-term survivors were observed among allo-SCT recipients

I believe there is no role for allo-SCT in the modern era in the RRMM setting. Ikeda T, et al.. Hematol Oncol 2019;37:586-94.

Challenges in RRMM therapy

Which drug Which Sequence

I will focus only on drugs approved for relapsed setting and few in trials that are quite promising…

Challenges in RRMM therapy

Which drug Which Sequence

I will focus only on drugs approved for relapsed setting and few in trials that are quite promising…

Myeloma cells carry specific proteins on their surface

Antibodie s

CD-38 - Daratumumab - Isatuximab

SLAM-7

- Elotuzomab

BCMA - Promote plasma cell survival - Transduction of signals, BAFF and APRIL - Advantage for myeloma cell growth/survival

CD-38 Antibodies

Selected Phase II/III Trials

Daratumumab & Isatuximab 100 80 60 40 20 0 D-RD

D-PD

D-VD

ORR, %

IKEMA

Pollux

Apollo

D-KD >VGPR, %

Castor Candor

ISA-PD ISA-KD PFS, m

ICARIA

Median Lines of therapy 1

1-3

Median follow up, m

11.6

Belantamab Mafodotin

DREAM-2

Humanized IgG1 anti-BCMA+ Toxin MMAF

DREAM-1

- 3.4 mg/kg P2D - ORR 60% - Ocular toxicity 60% - Thrombocytopenia 35%

Efficac y Adverse Events

DREAM-2

- > 3 lines of therapy Median 7 (3-21) - All triple class refractory - Approved dose is 2.5 /g/kg Long term follow up (13 m) - Median DoR 11.0 m (95% CI: 4.2–NR) - Response independt of cytogenetics or renal failure - Delay therapy no impact on clinical benefit

Duration of response

Overall survival

Lonial, Lancet Oncol 2020:21:207-

DREAMM-2: Corneal Events Belamaf 2.5 mg/kg; n = 95 • Ocular AEs common but manageable, majority of patients recover. 77% recovered from first keratopathy, 82% from reduction in BCVA Most recoveries occurred on treatment

Very important to monitor monthly with eye exam (asymptomatically cases) Dose reductions and delays did not impact efficacy

Keratopathy (MECs) 68/95 (72%)

In patients with keratopathy Grade ≥ 2 48% (29/60) had > 1 event

Symptoms (eg, blurred vision, dry eye) and/or a ≥ 2-line BCVA decline (better-seeing eye) 53/95 (56%) BCVA change to 20/50 or worse† 17/95 (18%) Discontinuation Due to corneal AE 3/95 (3%)

• Grade ≥ 2/3 corneal events increased with higher belantamab mafodotin Cta u ; time to initial grade ≥ 3 corneal event decreased with higher Cta us • Corneal event likelihood rose with previous history of dry eye, declined with higher blood levels of sBCMA Lonial S, ASH 2020 abs

The Future Role of Bispecific Antibodies

British Journal of Haematology, First published: 01 September 2021, DOI: (10.1111/bjh.17805)

Chimeric Antigen Receptor (CAR) modified T cells

KarMMa: Ide-cel in RRMM All ide-cell treated patients (N=128)

Tumor BCMA expression (≥50%)

85%

Extra medullary di sease

39%

Medi an ti me since diagnosis yrs ,

6 (1-18)

No. of pri or regimens,

6 (3-16)

≥7 prior antimyeloma regimens

38%

Response, %

Baseline characteristics

Respons e

100% 80% ORR=73% 33 60% % 20 40% 20 20% % 0% % All ide-cel treated (N=128) PR

VGPR

PFS 10.9 m (95%CI: 5.6-11.6) OS 24.8 m (95% CI 19.9-3.2) Medi an DOR … 10.9 m (95% CI: 9-11.4)

CRS and NT ≥1 CRS event, n(%)

107 (84)

Ma x gra de, n (%) 1/2

100 (78)

Medi an onset (ra nge), d

1 (1-12)

Medi an duration (range), d

5 (1-63)

≥1 NT event, n(%)

23 (18)

Ma x gra de, n (%) 1/2/3

11 (9)/ 7 (5)/ 5 (4)

Medi an onset (ra nge), d

2 (1-10)

Medi an duration (range), d

3 (1-26)

Anderson LD, et al. ASCO 2021. Abstract 8016.

PF S

CARTITUDE-1: Cilta-Cel in RRMM Characteristic (n=97) Age, median (range) years Bl a ck/African American, n (%) Prior lines of therapy, median (range)

61.0 (43–78) 17 (17.5)

Tri pl e-class refractoryc

6.0 (3–18) 85 (87.6)

Penta -drug refractoryd

41 (42.3)

Patients, %

Respons e 100%

80. 4%

50% 3.1 0% %

14. 4% PR

1st response … 1 m (0.9-10.7)

Medi an time to Medi an time to best response … 2.6 m (0.9-15.2) Medi an DOR … 21.8 m (95% CI, 21.8-NE)

Medi an follow-up…18 m (ra nge, 1.5–30.5) PFS … 66.0% (95% CI, 54.9–75.0) OS … 80.9% (95% CI, 71.4–87.6)

Side Effects, n(%) Neurotoxicity; any Grade

20 (20.6)

Neurotoxicity; > Grade 3

10 (10.3)

CRS

92 (94.8)

CRS, onset, days

7 (1-12)

CRS, duration, days

4 (1-97)

Usmani SZ, et al. ASCO 2021. Abstract 8005.

CAR T toxicities Management Tocilizumab/Dexamethasone

Methylprednisolone/Cyclophosp hamide/Seizure prophylaxis Cytopenias MAS (ferritin, IL-2R, NK cell activation, coags) Anakinra

Risk factors • Type of malignancy (ALL > DLBCL) • Tumor burden • Baseline inflammatory state • CAR T-cell (design, dose, expansion…)

Immunosuppression (IVIg; Antimicrobial prophylaxis) Long-term CAR T cells may remain for years (? late onset treatment-related effects) Brudno J, Kochenderfer, JH. Blood. 2016;127:3321-3330. Maude SL, et al. N Engl J Med. 2014; Davila ML, et al. Sci Transl Med. 2014; Lee DW, et al. Lancet. 2015; Teachey DT, et al. Cancer Discov. 2016; Turtle CJ, et al. J Clin Invest. 2016; Turtle CJ, et al. Sci Transl Med. 2016; Gust J, et al. Cancer Discov. 2017; Hay KA, et al. Blood. 2017; Neelapu SS, et al. N Engl J Med. 2017; Maude SL, et al. N Eng J Med. 2018; Park JH, et al. N Engl J Med.

Phase IIB STORM Trial

Selinexor (oral) 80 mg on days 1, 3 weekly every 4 wks Dexa (oral) 20 mg on days 1 and 3, weekly Inhibitor of Nuclear Export targeting XPO1

Phase III BOSTON Trial

Randomization

Selinexor

Bortezomib 1.3 mg/m2 Twice Weekly/Dexa 20 mg QIW Selinexor 100 mg Once Weekly/Bort 1.3 mg/m 2 Once Weekly+ Dexa (oral) 20 mg Twice Weekly

Synergistic activity Pis/IMiDs Experience with Selinexor - Fit vs frail PFS (13 vs 14 m) (Auner HW, ASH2020) - High-risk cytogenetics vs SR PFS (13vs 9 m), HR=0.7 p=08. (Richard S, ASH 2020) - First relapse.. PFS of 17 m (Mateos MV, AS 2020) Cha ri A, et.al. N Engl J Med 2019; 381:727-738. Gros icki S, et al. Lancet. 2020; 14;396:1563-1573.

Melflufen

Aminopeptidase targeting of myeloma cells

Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate

157 RRMM median age 65 yrs median lines of therapy; 5 All Refractory to Pom+/- Dara Triple class RRMM = 119 (76%) Refractory to alkylators = 92 (59%) Melflufen 40 mg IV every 28-days plus weekly dexa The overall response rate was 29% (26% in the triple-class–refractory)

- lipophilic, diffuses into the cell - Inside is cleaved by aminopeptidase to release alkylating load (entrapped inside the cell) - Within the nucleolus it induces DNA damage leading to cell death

Median follow-up of 14 months Median PFS 4.2 months OS 11.6 months

Ri chardson P, et a l. J Cl in Oncol. 2021 Ma r 1;39(7):757-767.

Venetoclax Arm 1: Venetoclax with dara and Dexa in t(11;14) RRMM (n=24) Arm 2 : VenDd + bortezomib (VenDVd) unselected RRMM

Bahlis N, et al. 2021 Aug 13;JCO2100443

Iberdomide

CELMoDs (Cereblon E3 Ligase Modulation Drugs)

- > 20-fold binding affinity to CRBN than LEN or POM _ More

efficient degradation of target proteins (Ikaros/Aiolos) - Antimyeloma and immune co-stimulatory activity on T/NK - Overcome resistance to len/Pom & Synergy bort/dara

- Side effects: Anemia (36%) Neutropenia (33%) Thromocy (14%) Fatigue (30%) Diarrhea (15%) Infection (> 30%)

Best Response, n (%) ORR ▪ sCR/CR ▪ VGPR ▪ PR

Iber + Dd (n = 27)

Iber + Vd (n = 23)

11 (42.3) 1 (3.8)/2 (7.7) 2 (7.7) 6 (23.1)

14 (60.9) 0/ 1 (4.3) 5 (21.7) 8 (34.8)

Fit Dara/Vel/dex Dara/Kar/dex Dara/Pom/dex

Lenalidomide

Refractory Frail

1st relapse

Sel/Vel/dex (sens) Elo/Pom/dex

Pom/Cytoxan/dex

Len Sensitive

Elo/Len/dex Kar/Len/dex Dara/Len/dex

Belnatamab (4 lines)

Good organ functions

Sel + Vel/dex or Kar/dex Panabinostat + Kar or Vel dex (PI refractory) Melflufen (4 lines) CAR-T Trials CAR T cells Bispecifics

≥ 2nd Relapse

Iberdomide Other targets (CD74, BRAF, etc…) Poor organ function

VDT-PACE/Melphalan + cells

Low counts, Creatinine, PCL, etc…

Chemotherapy (Adriamycin or alkylating) t(11:14)…Venetoclax

• MM is not a single disease…not every relapse need immediate therapy • MM therapy can and should be individualized

Few final thoughts

• Immunotherapies are changing MM landscape

• Goals of therapy need to be assessed in each stage • QoL & monitoring of side effects providing aggressive supportive care throughout the course of treatment are important today more than ever

Webinar Q&A

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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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AGENDA Changing the Course of Myeloma

Dr. Mikhael

Changing the Course of Myeloma in Maryland

Dr. Badros

Making Room for Hope and Joy

Bonnie Downing

How to Manage Symptoms and Side Effects

Amy Pierre

Audience Survey and Questions

Panel

Wrap up and thanks

Kelly Cox

Break

M-Power Baltimore: Changing the Course of Myeloma Dr. Joseph Mikhael IMF Chief Medical Officer Professor, Translational Genomics Research Institute (TGen) City of Hope Cancer Center

IMF Patient Empowerment Mission

Advancing early and equitable access to myeloma information, screening and treatment in vulnerable communities worldwide

African American Initiative The IMF African American Initiative is one important portion of the IMF’s Patient Empowerment Mission

SUPPORT

Many groups have sought to reach out to the African American myeloma community HOWEVER

The IMF is ideally poised to make a difference due to its unique mission and presence in the community

AWARENESS

RESEARCH

EDUCATION 84

The IMF African American Initiative The core vision of the IMF African American Initiative is to improve the short and long-term outcomes of African American patients through engagement of the community, education of health care providers, and support of patients ⚫

The overall objective of the IMF African American initiative is to improve outcomes in African American patient care by: ⚫

⚫

⚫ ⚫

actively engaging the African American community in a better understanding of myeloma educating the primary health care community regarding early and accurate diagnosis of myeloma supporting the Hematology Oncology community in their care of African American patients with myeloma

M-Power Baltimore Website: m-powerbaltimore.myeloma.org

Be M-Powered YOU Can Change the Course of Myeloma in Your Community

Ask if you should be screened @#$ %

#!? %^

Speak to your doctor about your risk Know the symptoms

Talk to friends & family about what you’ve learned about Multiple Myeloma

Community Outreach • Social Media Campaigns including Black History Month • M-Power Website with Toolkit • Patient Stories • Community Workshops • Myeloma Made Simple video • Teaming up with local organizations to provide community ed particularly in churches • Post ASH Facebook Live •

Kappa Alpha Psi Black Health Matters Summit booth

Myeloma Toolkit

M-Power Website

Education for Primary Care Providers Remember that there is typically a DELAY in diagnosis of myeloma in all patients The delay is LONGER in African American patients for many reasons Our goal is to reduce this time delay by educating the primary care communities in these cities with a focus on: * Recognizing the signs and symptoms of myeloma * Discriminating myeloma from other diagnoses such as diabetes * Proper use of testing to capture the accurate diagnosis of myeloma * Guidance as to referral to Hematology and Oncology

Optimal Practices for Nurses and Physicians The IMF Nurse Leadership Board has published a paper for nurses in the care of myeloma patients who are African American Similarly, a group of physicians are working on a similar paper for the physician community Key themes include: * Knowing the facts about myeloma in the African American community * Practical tools to facilitate care including the use of resources * Culturally competent care * Clinical trial participation

Current and Upcoming Geographies

M-Power Community Workshops Adjacent, targeted states States under consideration for 2022 Myeloma voices

Please Reach Out To Us! Website myeloma.org IMF InfoLine 800 452 CURE (2873) Website m-powerbaltimore.myeloma.org

Website www.umgcc.org/community Phone 800 821 1535

Changing the course of MM in Baltimore/MD Ashraf Badros, MB; ChB Professor Of Medicine Director of Multiple Myeloma Service Greenbaum Comprehensive Cancer Center University of Maryland

Changing the course of MM in Baltimore/MD

• Multiple myeloma is a rare cancer

• MM is more common in black communities • There are serious health disparities

Changing the course of MM in Baltimore/MD • Eliminate the stigma surrounding cancer “the disease” • Don’t keep this a secret from your family • Open conversations; • let them know that MM is out there and there’s a lot that can be done about it • I think that’s really the best way that we can educate and reach everyone

Changing the course of MM in Baltimore/MD • Empower our patients • Trust; it’s very important to communicate honestly and provide options • With new therapies, treatment options are changing rapidly • Update response criteria • Risk assessment • Disease Monitoring

Changing the course of MM in Baltimore/MD • Access to treatment • Perhaps one of the most important aspects of cancer care • Prioritizing access to treatment ”optimal” for all patients

• Increasing Diversity in Clinical Trials • Overcome distrust of clinical trials among Black communities • Clinical trials can be a life-saving resource for many.

We have done studies where we show that if black patients receive the same therapy their outcome is even better than whites (younger age, favorable biology,

A Patient Journey over 11 Years Venetoclax CyBorD x 6

Selinexor + KPD

DVT-PACE x 2 SCT x 2

KCD Iberdomide

Oprozomib Pom+D Lenalidomide

Belantamab

KCD + P

DRD

LD + IDE-CEL

Changing the course of MM in Baltimore/MD Our Mission as a community (physicians, nurses, patients and advocates…) • Raise awareness about the disease • Establish the highest standard of care • Make available promising clinical trials • Offer support throughout MM journey • Explore & overcome disparity in care • Build a family for support/shared experiences

MAKING ROOM FOR HOPE & JOY IN THE BATTLE B O NNIE D O W NING , M S

P A TIENT A D V OC ATE B A L T IMOR E, M D

My Diagnosis

Living the dream

H PE

My Diagnosis

✓ Back Pain ✓ Extreme Fatigue

✓ Weight Loss

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

My Diagnosis

Stem Cell Transplant Clinical Trial

→ Remission!

My Diagnosis

Remember: ❖ Develop an ongoing relationship with a Primary Care Physician ❖ Don’t hesitate to communicate your concerns ❖ Work with a myeloma specialist ❖ Call the InfoLine if you need help finding one! 800-452-CURE (2873)

HOPE

20 Years Later… I surround myself with messages of hope

H PE

…and Make Time for Joy

CRAZY STORM – BEAUTIFUL RAINBOW

How to Manage Myeloma Symptoms & Side Effects Amy E. Pierre, RN, MSN, ANP-BC Memorial Sloan Kettering Cancer Center, Flatiron Health & IMF Nurse Leadership Board

Your Care Consists of… MYELOMA TREATMENT

SUPPORTIVE THERAPIES

• Rapid and effective disease control

• Prevent disease- and treatmentrelated side effects

• Durable disease control

• Optimize symptom management

• Minimize side effects

• Improved overall survival Allow for Good Quality of Life

116

Myeloma and Treatments Both Contribute to How You Feel Patient Reported Symptoms

Psychological

Physical • •

• • • •

•

Depression

•

Anxiety

•

Sleep Disturbance

•

Decreased Cognitive Function

•

Decreased Role & Social Function

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

Financial •

Financial burden (80%)

•

Financial toxicity (43%)

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Deep Vein Thrombosis (DVT ) and Pulmonary Embolism (PE) Risk Factors Personal or family history Lifestyle (obesity, smoking, inactivity) Medical (medications, surgery

Symptoms

Swelling, tightness, ache/pain, change in color or temperature Chest or shoulder pain Shortness of breath, difficult/labored breathing Anxiety Rapid heart rate

Provider Management Adjusting medications and schedules (weekly steroids, types of chemo) Prescribing blood-thinning medications according to assessed risk (aspirin, warfarin, heparin or Direct Oral Anticoagulant[DOAC]) Anti-embolism stockings (elastic stockings)

Self Management

Lifestyle changes (stop smoking, weight mgmt) Activity; Moving frequently when sitting long periods; Travel precautions

Report DVT and PE symptoms immediately! These are considered a medical emergency & require immediate care.

GI Symptoms Diarrhea and Constipation: Prevention & Management • Diarrhea may be caused by – Laxatives, antacids with magnesium – Antibiotics, antidepressants, others – Milk thistle, aloe, cayenne, saw palmetto, ginseng – Sugar substitutes in sugar free gum

• Increase fluid intake – 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

Discuss GI issues with health care providers to identify causes of and make adjustments to medications and supplements.

• Increase fiber – Fruits, vegetables, high fiber whole grain foods – Fiber binding agents – Metamucil®, Citrucel®, Benefiber®

• Increase fluid intake – to work with fiber, also good for kidneys

Understanding Changes to Kidney/ Renal Function Risk Factors • Active multiple myeloma (light chains, high calcium) • Other medical issues (ex: Diabetes, dehydration, infection) • Medications (MM treatment, antibiotics, contrast dye)

Prevention • Drink, Drink, Drink • Avoid certain medications, when possible

Treatment • Treatment for myeloma • Hydration • Dialysis

Many myeloma patients will experience kidney function problems at some point; it is important to protect your kidney function early and over time.

Myeloma Cells Can Cause Damage To Bones Approximately 85% of myeloma patients develop bone disease • Protecting bone health – Nutrition – Weight-bearing activity – Medications • Vitamin D • Calcium (if approved by doctor) • Bone strengthening agents: Zometa® zoledronic acid, Aredia (pamidronate), or Xgeva® denousamab)

• Report new pain to your health care provider

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

Most myeloma patients will experience bone involvement at some point; it is important to protect your bone health

Figure 1. Bones at Highest Risk of Being Affected by Multiple Myeloma

Peripheral Neuropathy (PN) Management • Peripheral neuropathy: damage to nerves in extremities (hands, feet, or limbs) – – – – – –

Numbness Tingling Prickling sensations Sensitivity to touch Muscle weakness Burning pain or cold sensation

Report symptoms of peripheral neuropathy early to your health care provider; nerve damage from PN can be permanent if unaddressed Fa i man B, et a l. CJON. 2017;21(5)suppl:19-36. Ta riman, et al. CJON.2008;12(3)suppl:29-36.

• 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 122

122

Steroid Side Effects and Management Steroid Side Effects • Irritability, mood

swings, depression

• Blurred vision, cataracts • Flushing/sweating

• Difficulty sleeping

(insomnia), fatigue

• Increased risk of

infections, heart disease

• Stomach bloating, hiccups,

Take with food Stomach discomfort: Over-the-counter or prescription medications

Medications to prevent shingles, thrush, or other infections

• Weight gain, hair thinning/loss,

skin rashes

• Increase in blood sugar

levels, diabetes

• Increase in blood pressure,

water retention

Consistent schedule (AM vs. PM)

heartburn, ulcers, or gas

• Muscle weakness,

cramping

Managing Steroid Side Effects

Steroids help kill myeloma cells. Do not stop or adjust steroid doses without discussing it with your health care provider.

Infection Prevention & Treatment Compromised immune function comes from multiple myeloma and from treatment Good personal hygiene (skin, oral) Environmental control (wash hands, avoid crowds and sick people, etc) Growth factor (Neupogen [filgrastim]) Immunizations (NO live vaccines) Medications (antibacterial, antiviral)

COVID: The Best Way to Prevent Illness Is to Avoid Being Exposed to the Virus Spread mainly through respiratory droplets that are produced by cough, sneezing and talking.

❖ Get COVID Vaccine ❖ Wear a Mask ❖ Avoid Crowds, Sick People, Unvaccinated ❖ Physical Distance & Outdoors

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

❖ Wash Your Hands

Infection is serious for myeloma patients!

124 CDC website. How to Protect Yourself & Others. Accessed October 22, 2020.

ASH 2017 Abstract #903

Fatigue, Anxiety & Depression All can affect quality of life and relationships

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

• Anxiety reported in >35% • Depression nearly 25%

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

• 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 Burden Financial burden comes from ⚫

Medical costs

Premiums Co-payments Travel expenses Medical supplies

⚫

Prescription costs

⚫

Loss of income

o o o

o o

Funding and assistance may be available…

Ask about a social worker, financial or nurse navigators at your hospital or clinic for assistance.

contact the IMF Infoline for guidance at: 800-452 CURE (2873) or infoline@myeloma.org

Time off work or loss of employment Caregiver time off work

126

Discuss Your Priorities and Treatment With Your Healthcare Team Take Time to Consider Your Preferences Before an Appointment Ask Important Questions at Your Appointments • What Can I Expect Now? • What Can I Expect In the Future? Have these conversations…

• Whenever your treatment stops working • Whenever you start a new treatment

• Whenever there is a change in your life priorities • Whenever you have a question or concern

Available for download at myeloma.org

IMF has many free resources to help you

http://m-powerbaltimore.myeloma.org

IMF TV

http://myeloma.org IMF InfoLine: 1-800-452-CURE | 9am to 4pm PST

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Please Reach Out To Us! Please Reach Out To Us! Website myeloma.org IMF InfoLine 800 452 CURE (2873) Website m-powerbaltimore.myeloma.org

Website umgccc.org/community Phone 800 821 1535 129

Webinar Q&A

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•

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

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Workshop Video Replay & Slides

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