2024 Boca Raton Patient and Family Seminar - Saturday Slide Deck

2024 Boca Raton Patient and Family Seminar

March 15 & 16, 2024

The IMF Support Group Team is Here For You!

Shared Experiences Help to Better Understand the Myeloma Journey

• Support Groups Empower Patients & Care Partners with information, insight, & hope

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

Support.myeloma.org

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

Reach out to us at

SGTeam@myeloma.org

Local

Support Groups: You Are Not Alone!

 Miami Multiple Myeloma Support Group

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

 Melbourne Multiple Myeloma Support Group

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

Palm Beach County Multiple Myeloma Support Group

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

 Maitland Multiple Myeloma Support Group

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

 Fort Myers Multiple Myeloma Support Group

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

 Hollywood Multiple Myeloma Support Group

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

 Jacksonville Multiple Myeloma Support Group

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

Local Support Groups: You Are Not Alone!

 Brooksville / Nature Coast Multiple Myeloma Support Group

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

 Tampa CentralMultiple Reasons Support Group

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

 North Tampa Multiple Myeloma Support Group

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

 Naples Multiple Myeloma Support Group

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

 Tampa Bay/St Petersburg Multiple Myeloma Educational Group

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

Local Support Groups: You Are Not Alone!

 Palm Coast Multiple Myeloma Support Group

 Meets in-person on the 2nd

Thursday of each month at 3:30PM

 Ocala Multiple Myeloma Support Group

 Meets in-person on the 2nd

Saturday of each month at 11AM

 Sarasota Multiple Myeloma Network & Education Group

 Meets in-person on the 4th

Friday of each month at 11AM

 The Villages Multiple Myeloma Support Group

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

 Panama City Multiple Myeloma Support Group

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

 Tallahassee Multiple Myeloma Support Group

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

IMF – Special Interest Virtual Groups

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

 Las Voces de Mieloma

 Designed for Spanish speaking patients only

 Living Solo & Strong with Myeloma

 Designed for patients without a care partner

Coming Soon!

Care Partners Only

 Designed to address the needs of care partners only

 Smolder Bolder

 Created for people living with Smoldering Multiple Myeloma

 MM Families

 High Risk Multiple Myeloma

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

 MGUS 4 Us

 Created for people living with MGUS

 For patients/care partners with young children

EVALUATION

Please be sure to complete your program evaluation today.

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

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

Our team will collect all responses at the end of the day!

We greatly appreciate your time and feedback!

President & CEO Address

Yelak Biru

28-year Myeloma Survivor Patient

International Myeloma Foundation

The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure.

In November 2023, Susie stepped down from her leadership position to take time from what has been her 24/7 commitment to the IMF since •

Brian Novis

Susie Durie

Brian G.M. Durie, MD

In 2021 Poornima was Diagnosed with Multiple Myeloma

She had many questions!

Emotional

• This can't be happening to me.

• What will the future hold? How will this progress?

• Will treatment be painful? Will I be able to handle the side effects?

• How long do I have? What will my final days be like?

• Even after treatment, the fear of the cancer coming back can be very real.

• No one understands what I'm going through."

Medical

• What kind of doctor should I see?

• What is myeloma? What stage is it? What is my prognosis? Is it curable?

• What tests do I need to have done?

• What are my treatment options? What are the side effects of treatment?

• Are there clinical trials I can participate in?

• Will I be able to work and live a normal life?

Support

• What resources are available to help me cope with this disease?

• How will I pay for treatment?

• What kind of support groups are available?

• How do I talk to my family and friends about my diagnosis?

In 1995 Yelak was Diagnosed with Multiple Myeloma

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

Purpose

Our calling is clear: to fight alongside you every step of the way.

The Why of the IMF: A Patient-Centric Approach

You have the right to live life to the fullest. This is why a cure alone isn't enough.

• Patient-centric approach

• Information and resources

• Support systems

Is it Enough?

The IMF has made incredible strides in empowering patients. Imagine a newly diagnosed patient, overwhelmed and scared.

• Clear, concise information and Education

• Support groups

• We advocate on your behalf.

• We do and conduct research.

These are vital steps, but…

The answer is a resounding NO, we are not doing enough!

More Should Be Done, and Here’s How the IMF Plays a Role

• We envision a future where patients can thrive, not just survive.

• Myeloma shouldn't dictate your quality of life.

• You shouldn't have to choose between effective treatment and debilitating side effects.

• C U R E

Early Diagnosis

High-quality

Strategic collaboration

5

Research

that matters most to patients happens

Our Strategy Flywheel

4+ Generations

Millennials (22-41)

Gen-X (42-57)

Baby Boomers (58-75 Traditionalists (75-95)

1. Primary Destination

• Research, Support, Education, Advocacy

• Omnichannel way – Online, In Person, Telephone

2. Patients & Care Partners

• Shorten time from diagnosis to Hope –Time To Hope (TTH)

• Increase Time To next Treatment (TTT)

• Education

• Connection

• Overcome obstacles to access

• Address health equity

3. Healthcare Providers

• Timely Information + Education

• Treatment guidelines for newly diagnosed & initial relapse

• Expert 2nd opinion

4. Partner Ecosystem

• Credible partners in development, access, and policy

• Clinical trials – remove entry barrier + increase patient participation

• Research – Novel testing & therapy approaches

• Black Swan Research Initiative – BSRI

• Immunotherapy Data Marketplace

5. Sustainable Growth

• Strategic Plan

• Digital Innovation

• Investment in our People

• Bold Collaboration

6. Expand Capability

• Research

• Technology and Data

EVALUATION

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

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

We greatly appreciate your time and feedback!

What is the Future of Myeloma?

Saad Usmani, MD

Memorial Sloan Kettering Cancer Center

New York, NY

The Future of Multiple Myeloma

Saad Z. Usmani, MD MBA FACP FRCP FASCO Chief of Myeloma Service

Professor, Weill Cornell Medical College, Cornell University

Disclosures

• Research funding: Abbvie, Amgen, Array Biopharma, BMS, Celgene, GSK, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDX, Takeda.

• Consulting: Abbvie, Amgen, BMS, Celgene, EdoPharma, Genentech, Gilead, GSK, Gracell Therapeutics, Janssen, Oncopeptides, Sanofi, Seattle Genetics, SecuraBio, SkylineDX, Takeda, TeneoBio.

It Is Not a Matter of How, It Is a Matter of When We Will #CureMM!

Towards Curing Myeloma by 2034

• Comprehensively study the molecular and immunobiology of disease evolution and progression in MM.

• Recognize ‘real’ myeloma at the smoldering stage and intervene early for a defined duration of time.

• Pick different strategies for different disease biology and immune status.

• Incorporate frailty assessments in this algorithm.

• Optimize sequencing of existing therapies and incorporation of select novel MoAs based on disease biology.

• Accurately assess sustained minimal residual disease (MRD) negativity.

• Utilize novel imaging and novel peripheral blood assessments.

• Use MRD assessments guide treatment time and treatment strategy.

• Use Sustained MRD to stop treatment.

• Pay attention to supportive care.

• Address both short-term and long-term sequelae of treatments.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

The Road to Victory….

CAR, chimeric antigen receptor; HDT, high-dose therapy; OS, overall survival; PD-1, programmed cell death 1; PD-L1, programmed cell death-ligand 1; PFS, progression-free survival; R/R, relapsed/refractory.

1. Laubach J, et al. Annu Rev Med. 2011;62:249-264. 2. Rajkumar SV. Am J Hematol. 2020;95(5):548-567. 3. Palumbo A, et al. N Engl J Med. 2014;371(10):895-905. 4. Zanwar S, et al. Blood Cancer J. 2020;10(8):84. doi: 10.1038/s41408-020-00350-x. 5. US Food and Drug Administration. FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma. Updated August 6, 2020. Accessed May 6, 2021. 6. US Food and Drug Administration. FDA approves first cell-based gene therapy for adult patients with multiple myeloma. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-basedgene-therapy-adult-patients-multiple-myeloma. Updated March 27, 2021. Accessed May 17, 2021.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

NDMM: Principles of Therapy

• Picking the right strategy that gives the highest likelihood of the best depth of response in the first year of diagnosis is extremely important for survival outcomes.

– MRD 10-5 >> MRD 10-6 >> Sustained MRD 10-6

• Optimize induction, consolidation and maintenance based on:

– Disease biology (what kind?).

– Disease burden (how much?).

– Patient characteristics (PS, co-morbidities, frailty).

– Patient preference.

• Never under-treat, put your best foot forward!

– Especially true for high risk NDMM (HR-NDMM)

• Do not forget supportive care measures: bone health, infection prevention, pain management, physical therapy and rehabilitation, mental health.

Staging: Combining Nature with Size

Stage1 R-ISS1

Serum albumin ≥3.5 g/dL-1

I

Serum β2M <3.5 mg/L-1

No high-risk cytogenetics

Normal LDH level

II Not stage I or III

III Serum β2M >5.5 mg/L-1

High-risk cytogenetics: t(4;14), t(4;16), or del(17p) or elevated LDH

Risk2 Features

Trisomies

Standard

High

t(11;14) t(6;14)

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

Del(17p)

p53 mutation

Gain/Amp 1q

High plasma cell S-phase

GEP high-risk signatures

Circulating Plasma Cells

Elevated LDH/EMD

Ultra-High Risk 2 or more features

Stage1 R2-ISS3

I 0 Points (Low Risk, 19% pts)

II 0.5-1 Points (Low-Intermediate Risk, 31% pts)

III 1.5-2.5 Points (Intermediate-High Risk, 41% pts)

IV 3-5 Points (High Risk, 9 % pts)

POINTS: ISS III= 1.5, ISS-II = 1, Del17p =1, elevated LDH =1, Chromosome 1q21+ = 0.5

High-Risk Consensus Definition for Trials4

• R-ISS III

• R-ISS II with 1q21+, Del17p, t(14;16), t(14;20)

• Circulating PCs >5%

• Extramedullary disease

Treatment Paradigm For Newly Diagnosed

SWOG S0777: RVd Versus Rd in Patients Without Immediate Intent for ASCT1

RVd

Presented

IFM 2009 Study: Early vs Late ASCT

3x R ASCT

3x

RVd 21-day Cycles

R: 25 mg d 1 – 14

V: 1.3 mg/m2 d 1, 4, 8, 11

2x

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

R Maintenance

R: 10-15 mg/d for 13 cycles

ORR, MRD, TTP, OS, safety

Superior PFS With ASCT vs RVd Alone

RVd + transplant was superior to RVd alone, even with undetectable MRD at 10-6

Presented by:

MRD, minimal residual disease.

Perrot A. Presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; Abstract 143.

DETERMINATION: study design and patient disposition

DETERMINATION: Delayed vs Early Transplant with Revlimid Maintenance and Antimyeloma Triple Therapy

RVd cycle 1 (N=729)

Randomization (N=722)

Stratified by:

ISS disease stage

Cytogenetic risk

Arm A: RVd-alone (N=357)

Arm B: RVd+ASCT (N=365)

RVd cycles 2-3

Stem cell collection

RVd cycles 4-8

R maintenance (N=291)

RVd cycles 2-3

Each RVd cycle (21 days):

R 25 mg/day PO, days 1-14

V 1.3 mg/m2 IV/SC, days 1, 4, 8, 11

Dex 20/10 mg PO, days 1, 2, 4, 5, 8, 9, 11, 12

Stem cell collection

Melphalan 200 mg/m2 + ASCT (N=310)

RVd cycles 4-5

Induction ± ASCT + consolidation treatment duration = ~6 months

R maintenance (N=289)

Lenalidomide maintenance

Months 1-3: 10 mg/day

Month 4 onwards: 15 mg/day

• d/Dex, dexamethasone; DOR, duration of response; ISS, International Staging System; IV, intravenous; PO, orally; R, lenalidomide; SC, subcutaneous; TTP, time to progression; V, bortezomib

Primary endpoint: PFS

Secondary endpoints: response rates; DOR; TTP; OS; QoL; safety

DETERMINATION: Endpoint Readouts

(Median follow-up 70 months)

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

DETERMINATION Trial: PFS by Risk

GRIFFIN: Daratumumab Plus Lenalidomide, Bortezomib,

and Dexamethasone in Transplant-Eligible NDMM – 24 Months of Maintenance

Study design

Key eligibility criteria: TE NDMM; 18–70 years; ECOG PS 0–2; CrCl ≥30 mL/min2

D-R

N=207

Induction: C1–4 Consolidation: C5–6a Maintenance: C7–32b

D-RVd

D: 16 mg/kg iv D1, 8, 15

R: 25 mg po D1–14

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

d: 20 mg po D1, 2, 8, 9, 15, 16

RVd

R: 25 mg po D1–14

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

d: 20 mg po D1, 2, 8, 9, 15, 16

21-day cycles

D-RVd

D: 16 mg/kg iv D1

R: 25 mg po D1–14

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

RVd

Patient disposition

n (%)

D: 16 mg/kg iv D1 q4w or q8wc

R: 10 mg po D1–21; C7–9

d: 20 mg po D1, 2, 8, 9, 15, 16 R

R: 25 mg po Days 1–14

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

d: 20 mg po D1, 2, 8, 9, 15, 16

Stem cell mobilization with G-CSF ± plerixafor

• Primary endpoint: sCR by end of consolidation

D-RVd (n=104) RVd (n=103)

Treated with maintenance therapy 90 (87) 70 (68)

Completed maintenance therapy

15 mg po D1–21; C10+

R: 10 mg po D1–21; C79

15 mg po D1–21; C10+

21-day cycles 28-day cycles

67 (64) 44 (43)

Discontinued treatment during maintenance therapy 21 (20) 21 (20)

Adverse

• Secondary endpoints: MRD negativity (NGS 10-5), ORR, ≥VGPR, CR, PFS, OS

aConsolidation initiated 60–100 days post transplant; bPatients who complete maintenance cycles 7–32 may continue single-agent lenalidomide thereafter; cProtocol amendment allowed q4w dosing option. Phase 2 trial – patient enrollment between December 2016 and April 2018

Laubach JP, et al. ASH 2021, Virtual Meeting. Abstract 79

Presented

GRIFFIN: Daratumumab

Plus Lenalidomide, Bortezomib, and Dexamethasone in Transplant-Eligible NDMM – 24 Months of Maintenance

RVd ± Daratumumab x 6 cycles (4 pre- and 2 post ASCT)  ASCT  R ± Daratumumab maintenance x 2 years  optional R maintenance

Voorhees PM et al. Lancet Haematology 2023.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

MRD assessed in the ITT population

GRIFFIN: Longitudinal Outcomes

PERSEUS: DVRd vs VRd in Transplant-Eligible NDMM

Eligibility

• Transplant-eligible NDMM

• Age 18 – 70

• ECOG PS 0 – 2

4 cycles induction 2 cycles consolidation Transplant

28-day cycles

n = 355

R VRd

n = 354

28-day cycles

DVRd VRd

DVRd

Mel200 + ASCT

Induction/Consolidation Schedule

D: 1800 mg SC days 1, 8, 15, 22 in cycles 1-2, days 1, 15 in cycles 3-6

V: 1.3 mg/m2 days 1, 4, 8, 11

R: 25 mg PO days 1 – 21

d: 40 mg PO/IV days 1-4, 9-12

Primary endpoint: PFS

Key secondary endpoints: CR rate, MRD, OS

Maintenanc e until PD

DVRd VRd

Key Baseline Characteristics

n = 355 n = 354

Median age (range), y 61 (32 – 70)

High risk cytogenetics, n (%) 76 (21.4)

59 (31 – 70)

78 (22.0)

Extramedullary disease, n (%) 15 (4.2) 16 (4.5)

ISS stage, n (%) I II III

186 (52.4)

114 (32.1)

55 (15.5)

178 (50.4)

125 (35.4)

50 (14.2)

• ASCT, autologous stem cell transplant; CR, complete response; DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; DR, daratumumab and lenalidomide; ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; IV, intravenous; MRD, minimal residual disease; NDMM, newly diagnosed multiple myeloma; PFS, progression-free survival; PS, performance status; OS, overall survival; PO, by mouth; R, lenalidomide; SC, subcutaneous; VRd, bortezomib, lenalidomide, and dexamethasone.

PERSEUS: PFS and OS

Median follow-up 47.5 mo

The FORTE Trial

Multicenter, Randomized (1:1), Open-Label, Phase 2 Study

Is MEL200 better than 16 additional weeks of KRD?

FORTE. Updated November 3, 2022. https://classic.clinicaltrials.gov/ct2/show/NCT02203643

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

FORTE: Depth of Response and PFS

Progression-Free Survival

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

MRD Negativity

12 58% 35%

 ASCT 43% 25%

† OR KRd  ASCT vs KRd 12: 1.69 (95% CI 1.07 – 2.66, P = .024).

Progression-Free Survival With Sustained MRD Negativity

. 2021;22(12):1705-1720.

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

Daratumumab-KRd for NDMM

Study/Phase Patient Characteristics Responses PFS data Safety (Grade ¾)

Landgren O et al

JAMA Onc 2021

Phase II

8 cycles

N=41

High-risk = 49% (included gain 1q)

Median age: 60 years

Costa LJ et al

JCO 2022

Phase II

4 cycles

Bhutani M et al

ASH 2022

Phase II

8 cycles

ORR = 100% >CR rate = 95%

MRD-ve at 10-5 = 71%

N=123

High-risk = 57% (included gain 1q)

Median age: 60 years

N=23 (of 39)

High-risk = 43% (included gain 1q)

Median age:

ORR = 100%

>CR rate = 39%

MRD-ve at 10-5 = 80%

1-year PFS rate 100% Neutropenia 27%, Rash 9%

Lung infection 7%

Increased ALT 4% No TRM

2-year PFS rate 87% Lung infection 6% VTE 3% No TRM

ORR = 100%

>CR rate = 65%

MRD-ve at 10-5 = 70%

Not reported Hypophosphatemia 30%

Neutropenia 13%, HTN 13%

COVID19 7% No TRM

Rates of ≥CR (best response on study) by cytogenetic risk status* in MASTER and GRIFFIN trials

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

MRD negativity by cytogenetic risk status* among patients who received D-KRd in MASTER and D-RVd in GRIFFIN

MRD minimal residual disease, D-KRd daratumumab plus carfilzomib/lenalidomide/dexamethasone, D-RVd daratumumab plus lenalidomide/bortezomib/dexamethasone, HRCA high-risk cytogenetic abnormality, CR complete response, NA not available.

*HRCAs include any of the following genetic abnormalities: del(17p), t(4;14), t(14;16), t(14;20), and gain/amp(1q21) (≥3 copies of chromosome 1q21). Patients were grouped into categories: standard risk (0 HRCA), high risk (1 HRCA), or ultra-high risk (≥2 HRCAs).

†For MASTER, data are for all enrolled patients with available MRD data.

‡For GRIFFIN, the D-RVd group included patients from the randomized phase (n = 104) and the safety run-in phase (n = 16). Patients were grouped by HRCA: 0 HRCA (n = 67), 1 HRCA (n = 34), or ≥2 HRCAs (n = 13). 6 patients were not evaluable for cytogenetic abnormalities.

IsKia Isa-KRd vs KRd in Transplant-Eligible NDMM

Eligibility

• Transplant-eligible NDMM

• Age < 70y

4 cycles induction 4 cycles consolidation Transplant

28-day cycles

N = 302

28-day cycles

n = 151

R KRd

n = 151

Isa-KRd KRd

Isa-KRd

Mel200 + ASCT

Induction/Consolidation Schedule

Isa: 10 mg/kg IV days 1, 8, 15, 22 in cycle 1,

10 mg/kg IV days 1,15 in cycles 2 – 4

K: 20/56 IV mg/m2 days 1, 8, 15

R: 25 mg PO days 1 – 21

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

Primary endpoint: rate of post-consolidation MRDnegativity in ITT population

Key secondary endpoints: post-induction MRD-negativity, PFS

Key Baseline Characteristics

Isa-KRd KRd

n = 151 n = 151

Median age (range), y 61 (55 – 66) 60 (54 – 63)

High risk by IMWGa 25 (18) 26 (19)

# of HRCAb, n (%) 0 1 2 or more Missing

R-ISS stage, n (%) I II III

R2-ISS stage, n (%)

78 (56)

49 (35)

13 (9) 11

50 (35)

82 (58)

10 (7)

75 (54)

49 (35)

15 (11) 12

34 (24)

45 (32)

52 (37) 8 (6)

48 (34)

85 (59) 10 (7)

35 (25)

47 (34)

51 (37)

6 (4)

• a. del(17p), t(4;14), and/or t(14;16); b. del(17p), t(4;14), t(14;16), gain or amp(1q).

• Isa, isatuximab; KRd, carfilzomib, lenalidomide, and dexamethasone; R-ISS, Revised International Staging System; Mel200, melphalan 200 mg.

IsKia: Responses

Post-consolidation MRD-Negativity in ITT population

Primary endpoint

•

MRD advantage with Isa-KRd retained across all subgroups

Subgroup analysis

MSK Approach to Transplant Eligible NDMM

ASCT-Eligible Patients

Patients with good PS and adequate organ function

Standard risk

Dara-VRd × 4 cycles

High risk*

Consider VRd or KRd ×4 cycles

For Insurance reasons

DaraKRd × 4 cycles

Stem cell mobilization; adequate stem cell harvest (≥8×10 6 CD34 cells/kg) as per MSK ABMT SOP ASCT

Consider

with induction regimen for HR-NDMM patients who do not achieve CR or better

Consider VDPACE for Bulky EMD or PCL

Cytoreduction Consider planned Auto/Allo for Ultra-high risk

ASCT, autologous stem cell transplant; CR, complete response; DVRd, daratumumab, bortezomib, lenalidomide, and dexamethasone; IMiD, immunomodulatory drug; PI, proteasome inhibitor; PS, performance status; Tx, treatment.

*By R-ISS staging (R-ISS II/III) and/or cytogenetics (t[4;14], t[14;16], or del[17p]), elevated LDH, primary plasma cell leukemia 1. Attal. NEJM. 2017;376:1311. 2. Voorhees PM. Blood 2020. Gay. ASH 2020. Abstr 294. 4. McCarthy. J Clin Oncol. 2017;35:3279. 5. Nooka. Leukemia. 2014;28:690. 6. Dimopoulos. ASH 2018. Abstr 301. 7. Usmani. Lancet Haematol. 2021 Jan;8(1):e45-e54.

MSK Approach to Transplant Ineligible NDMM

ASCT-Ineligible Patients

Patients with poor PS not related to disease, ejection fraction <50%, pulmonary function test values <50%, concomitant multiorgan amyloidosis

RVd-Lite1×8-12 cycles

Lenalidomide maintenance until progression3

Consider DVd or VCd or Rd if VRd or DRd is not appropriate (eg, renal failure or other comorbidities)

DRd2

IMiD/PI maintenance until progression for high risk4

Continue treatment until progression

• DRd, daratumumab, lenalidomide, and dexamethasone; DVd, daratumumab, bortezomib, and dexamethasone; VRd-Lite, modified VRd regimen.

• Adjust dosing of lenalidomide based on renal function. Consider empiric age-adjusted dose reductions for all regimens, as needed.4

• 1. O’Donnell. Br J Haematol. 2018;182:222. 2. Facon. ASH 2018. Abstr LBA-2. 3. Larocca. ASH 2018. Abstr 305. 4.Usmani. Lancet Haematol. 2021 Jan;8(1):e45-e54.

RVd-Lite

• Regimen (N=53)

– Lenalidomide: 15 mg po days 1 to 21

– Bortezomib: 1.3 mg/m2 SC 1× weekly on days 1, 8, 15, 22

– Dexamethasone

• If ≤75 years, 20 mg 2× weekly

• If >75 years, 20 mg 1× weekly

• Results

– 86% ORR

– 66% ≥VGPR

– Median PFS: 35.1 months

– Median OS: NR

– Median follow-up: 30 months

– Median age: 73 years (range: 65-91)

– PN: 62%

– Only 1 patient had grade 3 symptoms

• PN, peripheral neuropathy. O’Donnell et al. Br J Haematol. 2018;182:222-230.

Phase 3 MAIA Study: Daratumumab Plus Rd in NDMM

• Stratified by ISS (I vs II vs III), region (North America vs other), and age (<75 vs ≥75 y)

• Primary endpoint: PFS

• Secondary endpoints: ≥ CR rate, ≥ VGPR rate, MRD negativity, ORR, OS, and safety

Patients with ASCTineligible NDMM, ECOG

PS 0-2, CrCl ≥30 mL/min (N = 737)

R

Daratumumab 16 mg/kg IV (every-wk cycles 1-2; every-2-wk cycles 3-6; every-4-wk cycles 7+) +

lenalidomide 25 mg/d PO on d 1-21 +

dexamethasone 40 mg/wka PO or IV (n = 368)

28-d cycles until progressio n

Lenalidomide 25 mg/d PO on d 1-21 +

dexamethasone 40 mg/wka PO or IV (n = 369)

Demographics and Baseline Characteristics (ITT)

D-Rd (n = 368)

Rd (n = 369)

73 (50-90)

4 (1)

74 (20)

130 (35)

160 (43)

Male,

74 (45-89)

4 (1)

73 (20)

131 (36)

161 (44)

Type of measurable disease, n (%)

IgG

IgA

Otherd Detected in urine only

Detected as serumfree light chain only

Cytogenetic profile,e n/total n (%)

Standard risk

High risk

Median time since initial diagnosis of MM (range), months

225 (61)

65 (18)

9 (2)

40 (11)

29 (8)

271/319 (85)

48/319 (15)

231 (63)

66 (18)

10 (3)

34 (9)

28 (8)

279/323 (86)

44/323 (14)

0.95 (0.1-13.3)

0.89 (0-14.5)

ITT, intention-to-treat. aECOG PS is scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability. b2 patients had an ECOG PS score >2 (1 patient each with an ECOG PS score of 3 and 4). ISS stage is derived based on the combination of serum β 2-microglobulin and albumin; higher stages indicate more severe disease. dIncludes IgD, IgE, IgM, and biclonal. eCytogenetic abnormalities were identified by fluorescence in situ hybridization or karyotype testing; high risk was defined as having a t(4;14), t(14;16), and/or del17p abnormality . Note: percentages may not add up to 100% due to rounding.

MAIA Phase III ORRa

Median follow-up

Primary: 28.0 months1

Median follow-up

56.2 months

• D-Rd induced deeper responses, with significantly higher rates of ≥CR and ≥VGPR, compared with Rd

• With >28 months of additional follow-up, responses deepened with continued daratumumab therapy

VGPR, very good partial response; PR, partial response; OR, odds ratio.

aITT population. bP <0.0001; P values were calculated from the Cochran-Mantel-Haenszel Chi-Squared test.

1. Facon T, et al. N Engl J Med. 2019;380(22):2104-2115.

Note: percentages may not add up to the total due to rounding.

Presented

MAIA Phase III Updated PFS/OS

CEPHEUS: Study Design

• Phase 3 study of DARA-VRd versus VRd in transplant-ineligible NDMM

Induction/Consolidation

V: 1.3 mg/m2 SC

VRd

Days 1, 4, 8, 11

Key eligibility criteria:

• Transplantineligible NDMM or deferred

• CrCl <40 mL/min

• ECOG PS ≤2

1 R a

R: 25 mg PO Days 1-14

d: 20 mg PO/IV Days 1,2,4,5,8,9,11,12

DARA SC-VRd

DARA: 1,800 mg SC

Cycles 1-2 QW

Cycles 3-8 Q3W

VRd: Same as control

Maintenance

8 Cycles of 21 days

Rd

R: 25 mg PO Days 1-21

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

Primary endpoint:

• Overall MRD negativity rate at 10-5

Secondary endpoints:

• PFS

• Durable MRD negativity at 1-yr

• Response

• PFS2

• OS

28 day cycles

Zweegman S, et al. Trials in Progress Poster presented at ASCO Annual meeting. May 31-June 4, 2019. Chicago, IL. Abstract TPS8066. ClinicalTrials.gov Identifier: NCT03652064. Accessed 24 February 2022

IMROZ: Study Design

• Open-label, multicenter, randomized phase III trial

Stratified by ISS (I or II vs III vs unknown), age (<70 vs ≥70 yr)

Induction (4 x 42 ± 3 d cycles) Continuous (cycle 5 onward 4-wk ± 3 d cycles)

Isatuximab

10 mg/kg on d 1, 8, 15, 22, 29 in cycle 1; every 2 wk after + RVd*

Transplant-ineligible patients with NDMM (N = 440) IsaRd

3: 2

Isatuximab

10 mg/kg q 2 wk until cycle 18; Q4W after + Rd† Rd†

*RVd: lenalidomide 25 mg PO d 1-14, d 22-35, bortezomib 1.3 mg/m2 SC d 1, 4, 8, 11, 22, 25, 29, 32;

• Primary endpoint: PFS (IMWG criteria)

dexamethasone 20 mg PO/IV d 1, 2, 4, 5, 8, 9, 11, 12, 15, 22, 23, 25, 26, 29, 30, 32, 33.

†Rd: lenalidomide 25 mg PO d 1-21, dexamethasone 40 mg PO/IV weekly.

• Secondary endpoints: ≥ VGPR, CR, OS, MRD negativity

Cross over to Isa-Rd if progressio n on Rd

Orlowski. ASCO 2018. Abstr TPS8055. NCT03319667.

MSK Approach to Transplant Ineligible NDMM

ASCT-Ineligible Patients

Patients with poor PS not related to disease, ejection fraction <50%, pulmonary function test values <50%, concomitant multiorgan amyloidosis

Dara-RVd-Lite OR Isa-RVd-Lite × 6-8 cycles

[Fit or Intermediate Fit]

Lenalidomide maintenance until progression

Consider DVd or VCd or Rd if VRd or DRd is not appropriate (eg, renal failure or other comorbidities)

DRd1 [Frail ]

IMiD/PI maintenance until progression for high risk

Continue treatment until progression with either Len or Dara maintenance based on tolerability

• DRd, daratumumab, lenalidomide, and dexamethasone; Dara-RVd-lite, daratumumab, lenalidomide, bortezomib, and dexamethasone; Isa-VRd-Lite, isatuximab, lenalidomide, bortezomib, and dexamethasone.

• Adjust dosing of lenalidomide based on renal function. Consider empiric age-adjusted dose reductions for all regimens, as needed.4

• 1. Facon. ASH 2018. Abstr LBA-2. 3.

The Promise of T-cell redirection

BCMAbispecific

CAR, chimeric antigen receptor; MM, multiple myeloma

CAR T-cell therapy is not yet FDA-approved for patients with MM.

Presented

bispecific T-cell engager

3

Adapted from Cho S-F et al. Front Immunol. 2018;9:1821.

BCMA-

BCM A Myeloma cell T cell toxin

CD

Myeloma cell dying

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

CARTITUDE-6: Randomized, phase 3 in NDMM, transplant eligible (NCT05257083)

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

TRIUMpH Trial: Phase 3 BMT-CTN Study in HR-NDMM (In Development)

Presented by: Saad Z. Usmani, MD MBA FACP, @szusmani

A062104: Phase 2 trial investigating quadruplet induction followed by novel consolidation for Primary Plasma Cell Leukemia

Primary endpoint:

• Rate of MRD negativity (10-5) for t(11;14) patients post-induction

Key secondary endpoints:

• Rate of MRD negativity post-consolidation pooled across all patients

Registratio

INDUCTIO N 4 cycles

CONSOLIDATION 1 4 cycles

• Overall survival R

Teclistamab+

Talquetamab

CONSOLIDATION 2 4 cycles

MAINTENANC E 24 cycles

Teclistamab+

Talquetamab

KR

Ven-DKd or D-KRd*

Ven-DKd or D-KRd*

*Consolidation regimens will be the same as induction

Stratified on t(11;14) status and induction regimen t(11;14) with D-KRd vs. t(11;14) with Ven-DKd vs. non-t(11;14) with D-KRd

KRd, carfilzomib-lenalidomidedexamethasone

Newly diagnosed, standard risk concept

Induction Consolidation

Maintenance

DaraRVd x 4 cycles

1 : 1 R a n d o m i z a ti o n

ASCT

Tec+Talq (q2wk dosing as per RedirecTT-1) x 4 cycles

DaraLe n x 2 years

Len until PD

MRD assessment

Stem cell collection

MRD assessment

MRD assessment

• Co-primary endpoints: PFS (non-inferiority with planned superiority assessment) and cumulative incidence of severe infections

• Key secondary endpoints: OS, MRD-neg post consolidation, sustained MRD negativity after 2 yrs of maintenance

• QOL/PRO endpoint as correlative/exploratory endpoint: incorporate into design as an integrated biomarker with separate hypotheses, power statements and analysis plans

Presented by: Saad Z. Usmani, MD MBA FACP,

Conclusions

• Picking the right strategy that gives the highest likelihood of the best depth of response in the first year of diagnosis is extremely important for survival outcomes.

• Anti-CD38 monoclonal antibody-based quadruplets have helped optimize the ‘induction’ part of treatment by providing better depth of response, translating in to better PFS (GRIFFIN, CASSIOPEIA, PERSEUS, ?GMMG-HD7, ?IsKIA).

• Future strategies may incorporate:

– Biomarker-directed small molecules into induction.

– BsAb or CART as consolidation. – Fixed duration of maintenance. Presented by: Saad Z. Usmani, MD MBA

Building Translational Research Enterprise

Foci of Work

• Microbiome & Immune profiling.

• Computational Genomics

• Functional Imaging

• Blood-based MRD assessments

• Metabolomics

Collaborators

• Marcel van den Brink lab

• Sohrab Shah lab

• Vijay Joseph lab

• Omar Abdel-Wahab lab

• Jessica Chapman (Path/Clinical Proteomics)

• Kaz Murata (Path/Lab Medicine)

• Jason Lewis lab (Radiology)

• Gareth Morgan lab (NYU)

• Santosha Vardhana lab

• Samir Parekh (Mount Sinai)

• Madhav Dhodapkar (Emory)

Presented by: Saad Z. Usmani, MD MBA

Working Groups

• PCD Immune profiling/Microbiome

• PCD Genomics

• PCD Specimen Collection

• PCD Research Database

• PCD Imaging

Paula and Rodger Riney

MSKCC Myeloma Team – It Takes a Village!

Physicians:

• Parastoo Dahi (ABMT)

• Sergio Giralt (Deputy Chair, DHM)

• Alexander Lesokhin

• David Chung (ABMT)

• Hani Hassoun

• Malin Hultcrantz

• Neha Korde (Clinical Director)

• Heather Landau (ABMT)

• Kylee Maclachlan

• Sham Mailankody (Research Director)

• Dhwani Patel

• Sridevi Rajeeve

• Michael Scordo (ABMT)

• Gunjan Shah (ABMT)

• Urvi Shah

• Carlyn Tan

•

APPs:

• Isabel Concepcion

• Katie Jones

• Justina Kiernan (BER)

• Lori Lang (WES)

• Katelyn Kelly-Johnson (CMK)

• Jennifer Rielly

• Ashley Steinberger

• Jenna Wenzel

CTNs:

• Marcela Algave, RN

• Kelly Barnett, RN

• Jenna Blaslov, RN

• Julia Caple, RN

• Tara Sood, RN

• Ling Tran, RN

OPNs:

• Kelly Aliaga

• Grismer Canales

• Carolanne Carini (BER)

• Kathleen Considine (WES)

• Alexa Cracolici (MON)

• Kellie Donovan

• Mackenzie Galvin

• Anna Howard

• Kyla Lafond

• Michelle O’Hare (CMK)

• Pattie Scherer (BER)

PharmDs:

• Alice Wang

• Issam Hamadeh

Clinical Research Team:

• Miranda Burge

• Leah Gilbert

• Bianca Gonzalez

• Laura Guttentag (CRM, Myeloma)

• Selena Hamid

• Roger Huang

• Meredith Hyland

• Mosammed Kabir

• Emily Lei

• Guljar Nahar

• Alexis Nwakwo

• Garrett Preusz

• Anna Przemielewska

• Raisa Rahman

• Colin Rueda

• Jeannen Santos

• Tala Shekarkhand

• Felicia Slaton

• Clare Sullivan

• Kristina Vinzon-Baltazar

OCs:

• Fariha Ali

• Xavier Ayala

• Elhaji Ba

• Ruth Bien-aime

• Odali Espinal

• Eric Frazer

• Daniel Maldonado

• Krystal Soto

Service Manager/Admins:

• Kristen Hakuta

• Nicole Santiate

• Shaneeza Imran

• Gladys Acosta

EVALUATION

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

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

We greatly appreciate your time and feedback!

Myeloma Action Month

International Myeloma Foundation

Jason London

Manager, Marketing & Communications

BREAK

Breakout Sessions #1: Treatment

Approaches in Myeloma

A Newly Diagnosed: An Approach to Frontline Therapy

Peter Voorhees, MD

Royal Palms Ballroom

An Approach to Relapsed Myeloma

Gurbakhash Kaur, MD

Grand Oasis Ballroom

Novel Therapies for Relapsed Myeloma

By Gurbakhash Kaur, MD MA

Co-Director of Amyloidosis Program

Assistant Professor of Internal Medicine

UT Southwestern Medical Center

Active Drugs in Multiple Myeloma

Anti-SLAMF7 moAb

Anti-BCMA CAR-T

 Alkylators

 Steroids

 Anthracyclines

IMiDs

 Thalidomide

 Lenalidomide

 Pomalidomide

 Elotuzumab

 Cilta-cel

 Ide-cel

 ddBCMA

Anti-CD38 moAbs

 Daratumumab

 Isatuximab

 Felzartamab (MOR202)

 TAK 079

Proteasome

Inhibitors

 Bortezomib

 Carfilzomib

 Ixazomib

CELMoDs

 Iberdomide

 Mezigdomide

 SAR 442085

Anti-BCMA antibody drug conjugate

 Belantamab

Selinexor (XPO1 inhibitor)

Venetoclax (BCL-2 inhibitor)

 Lumicar Anti-BCMA bispecifics

 Teclistamab

 REGN-5458

 Alnuctamab

 Elranatamab

 TNB 383B

 AMG 701

Novel bispecifics

 Talquetamab (GPRC5D/CD3)

 Cevostamab (FcRH5/CD3)

Modified from Rajkumar SV © 2022

moAB: monoclonal antibody

Current MM Treatment Paradigm

Newly Diagnosed MYELOMA

Plateau remission

EARLY RELAPSE

CAR and BsAb

REFRACTORY RELAPSE 3+

Symptomatic MM

Front-line therapy

Induction

--- QUAD/Triplet Consolidation --- +/- SCT Maintenance

years

Frontline

Triplet/QUAD: Auto SCT Maintenance

2nd-line therapy

Early Relapse (1-3 Prior Lines)

Triplet

Delayed Transplant

OR CLINICAL TRIAL

3rd+ line therapy

Expected OS

<12 months

Late Relapse

BCMA - CAR, bispecifics

GPRC5D-Bispecific

Belantamab

Selinexor

Clinical Trial: BsAb, GPRC5D, etc.

Treatment Attrition in Multiple Myeloma

Patients reaching line of therapy, %

Attrition by line of therapy, %

Br J Haematol. 2016;175:252.

In every new line of therapy, 15%-35% of patients are lost

BMC Cancer. 2020;20:1087

Myeloma Tx At Glance

DP D

KR D

KP D

Selinexor Vd

PV D

Treatment Decision Rests On Interplay between

Disease Characteristics

Patient Characteristics

Treatment Characteristics

Clinical Nature of Relapsed Myeloma- All that Relapses is NOT the SAME

Biochemical relapse

Clinical Relapse

• Hypercalcemia

• Bone lesions

• EMD

• Renal Failure

Plasma cell Leukemia

Patient characteristics

Age Performance Status Comorbidities

Side effects and Toxicity to prior Therapy Support System

Distance to the Treatment Center

Disease Characteristics

High Risk Disease Cytogenetics

Depth and Duration of Response to Prior therapy

Timing of relapse

Aggressiveness of Relapse

• Extramedullary Disease

• Plasma Cell Leukemia

• Doubling time of the Myeloma Markers

Mechanism of Action (i.e Drug class, exposure vs refractory to a similar drug in the same class)

Frequency -> twice weekly, weekly, monthly  TIME TOXICITY

Side effects: (Peripheral Neuropathy, Cardiovascular/Renal Dysfunction, Blood counts, immune recovery)

Route of Administration (Intravenous, Subcutaneous, Oral)

Concurrent Supportive Care & Monitoring

$$$$$$$ Financial Burden

**Triplets are preferred

**Preferred Options,

Lenalidomide

Sensitive

KRD

DRD

ERD IRD

DVd

DKd

Isa Kd

SVd Kd, Rd,

Lenalidomide

Refractory

DPD

Isa PD

DKD

KPD

PCD

CyBorD

Results of Recent Phase III Randomized Studies in Relapsed Multiple Myeloma

Rajkumar SV. Am J Hematol 2022;97(8):1086. Martin T et al. Haematologica. 2022;107:2485. Dimoupolus. Blood (2022) 140

Richardson ASH 2022 Abstract . ICARIA Update. Richardson. International Myeloma Society. 2022.

Results of Phase III Randomized Studies in Relapsed Multiple Myeloma

1.

5.

1st line: VRD-auto-len maintenance until PD

2nd line : CD38-Kd until PD

3rd line: Len + K + CD38 refractory after 2 lines

Regimen should include2 drugs patient has not seen yet

4th: ___?????___________

Clinical Trials, Venetoclax in high BCL2/t(11;14), Bendamustine,

5th line and beyond – Immunotherapy, Clinical Trials

The majority of patients are becoming triple-class (PI + IMiD + CD38) refractory after 2-3 lines of therapy

Where does Immunotherapy fit into this algorithm?

Amazing Success in Immunotherapy for MM

Munshi COMy

Right patient, right treatment, right time

Teclistamab

Talquetamab

Elranatama b

2023

BCMA as a Target

BCMA: B Cell Maturation Antigen

Expressed on late memory

B-cells committed to PC differentiation and PCs

BCMA plays a role in survival of long-lived PCs

Cell lineage specific so avoids off target toxicity

CAR T-Cells

MM Cell Death

Cytotoxic Payload

Released Into Cell

T-Cell

Bispecific T-Cell Engagers BCM A

CD3

Bispecific Antibodies

T-Cell

CD3

Antibody–Drug

Conjugates

NKCells, Monocytes

Cho. Front Immunol. 2018;9:1821. Su. J Hematol Oncol. 2021;14:115. Tai. Expert Opin Biol Ther. 2019;19:1143. Slides adopted from

BCMA

Idecabtagene

Vicleucel (ide-cel, Abecma)

6 median prior LOT

35% HR Cytogenetics

39% EMD

84% Triple Refractory

ORR: 81%

CR/sCR: 39%

PFS: 12.2 mo

3/26/2021

4+ lines, including IMID, prior PI and anti-CD38 mAB

300-460 x 106

CAR-positive viable T-cells IV

Ciltacabtagene

Autoleucel (cilta-cel, Carvykti)

6 median prior LOT

24% HR Cytogenetics

13% EMD

88% Triple Class

Refractory

ORR: 98%

CR/sCR: 39%

PFS: 34.9 mo

2/28/2022

4+ lines, including prior IMID, PI and anti-CD38 mAB

0.5-1.0 x 106

CAR-positive viable T-cells/kg IV

Cell

Idecabtagene

Vicleucel (ide-cel, Abecma)

BCMA

Ciltacabtagene

Autoleucel (cilta-cel, Carvykti)

BCMA

6 median prior LOT

35% HR Cytogenetics

39% EMD

84% Triple Refractory

ORR: 81%

CR/sCR: 39%

PFS: 12.2 mo

CRS:

6 median prior LOT

24% HR Cytogenetics

13% EMD

88% Triple Class Refractory

ORR: 98%

CR/sCR: 39%

PFS: 34.9 mo

CRS: ICANS:

3/26/2021

4+ lines, including IMID, prior PI and anti-CD38 mAB

300-460 x 106

CAR-positive viable T-cells IV

2/28/2022

4+ lines, including prior IMID, PI and anti-CD38 mAB

0.5-1.0 x 106

CAR-positive viable T-cells/kg IV

What is it?

CRS and ICANS in a nutshell

CRS (Cytokine Release Syndrome)

Common symptoms

When does it happen?

How is it treated?

Will it get better?

A reaction from a strong immune response after treatment.

Fever, nausea, headache, fast heartbeat, low blood pressure.

Usually within the first week after treatment.

Car-t Construct specific

Supportive care, steroids, and a specific medication (tocilizumab).

Usually improves with treatment, severe cases may need intensive care.

ICANS (Immune Effector CellAssociated Neurotoxicity Syndrome)

A condition affecting the brain and nervous system after treatment.

Confusion, agitation, seizures, trouble speaking.

Often after CRS, usually within the first few weeks after treatment.

Supportive care, steroids, and sometimes other medications.

Often gets better with treatment, but some effects can last longer.

Adverse Events Associated With CAR-T

Adverse Event Description

Cytokine Release Syndrome (CRS)

A condition where the immune system reacts strongly, causing symptoms like fever, nausea, and in severe cases, problems with breathing and blood pressure.

Occurs 70-95% - all grade; <5% grade 3 or higher

Neurotoxicity

ICANS and Parkinsonian Type

This can include changes in behavior, confusion, seizures, and in rare cases, severe brain swelling

Rare cases of delayed Parkinsonian movement disorder, motor neuropathy, and CN palsies, may be irreversible

Any grade CRS: 20-25%, Grade 3 or higher in <5%

Low Blood Cell Counts

Infections

Hemophagocytic Lymphohistiocytosis (HLH)

This includes a decrease in the number of red blood cells (anemia), white blood cells (neutropenia), and platelets (thrombocytopenia), increasing the risk of infections and bleeding.

Due to a weakened immune system, there is a higher risk of catching infections.

**Requires supportive care like IVIG, prophylactic antibiotics**

A rare but serious condition where the body's immune system becomes overactive, attacking its own tissues and organs, leading to severe inflammation.

Bispecific Therapy

BCM A

CD3 T-Cell Myeloma Cell

 Antibodies with multiple binding domains

‒ Target different tumor antigens including BCMA, GPRC5D,FcRH5

‒ Also binds to immune cell targets including CD3 (T-cell)

Bispecific Therapy Approval Dosing

Teclistamab (Tecvayli™)

CD3 x BCMA 10/25/202 2

Step up Dosing: 0.06 mg/kg on Day 1, increase to 0.3 mg/kg on Day 4, and 1.5 mg/kg on Day 7; Day 14 and weekly thereafter: 1.5 mg/kg once ]

Recently, new FDA insight. Change to Q2 weekly after 6 months

Elranatama b (Elrexfio™)

CD3 x BCMA 8/14/2023

Step-up dosing: 12 mg on Day 1, 32 mg on Day 4, followed by 76 mg on Day 8

Day 8: 76 mg SQ followed by Day 15

76 mg once weekly SQ through Wk 24

Wk 25 onward: 76 mg every 2 wk

Talquetama b (TALVEY™) 8/9/2023

Image Credit: Modified from CCO Options

Step Up Dosing: Weekly option: Day 14 0.4 mg/kg SQ followed by 0.4 mg/kg SQ every wk

Immunotherapy What, When and How

What

• ADC

• Bispecifics

• CAR-T

WHEN Timing

HOW: Sequencing

• Early vs Late

• Impact of T cell exhaustion  move treatment earlier in order to have more robust T cells

• Bispecifics  CAR-T  ADC

• CAR-T Bispecifics  ADC

CombinationAlone or Together

• Combine mABs + Bispecifics

• Combine IMIDS

Mechanism of Action

Administration

Engages both the tumor antigen on myeloma cells and CD3 on T cells to induce T-cellmediated cytotoxicity.

Genetically modifies patient's T cells to express a chimeric antigen receptor (CAR) targeting a tumor antigen.

Manufacturing

Duration of

Response

Toxicity

Accessibility and Cost

Off-the-shelf, ready-to-use intravenous or subcutaneous injections.

Mass-produced, standardized product.

Continuous or repeated dosing to maintain response

Commonly associated with cytokine release syndrome (CRS) and neurotoxicity, usually milder compared to CAR-T.

Autologous therapy requiring cell collection, modification, and reinfusion.

Personalized, patient-specific production.

Potentially long-lasting responses with a single treatment.

Higher risk of severe CRS and neurotoxicity.

Patient Eligibility

Generally more accessible and less expensive than CAR-T therapy.

Broader eligibility, including patients with comorbidities or those ineligible for autologous stem cell transplant.

Requires specialized centers for administration, with higher costs.

Limited to patients who can undergo apheresis and tolerate the intensive treatment process.

Timing

•Can CAR-T Therapy be moved up in earlier lines of therapy

• KarMMA-3

• CARTITUDE -4

•Bispecifics

• Many trials are looking at this strategy right now

KarMMa-3: Phase III Trial of Ide-Cel vs SoC in R/R MM

International, open-label, randomized phase III trial

Lymphodepletion

Patients with R/R MM after 2-4 prior lines of therapy; including a PI, an IMiD, and daratumumab; disease progression in ≤60 days after last therapy

ECOG PS ≤1 (N = 386)

Stratified by age (<65 vs ≥65), prior therapies (2 lines vs 3-4 lines), and high-risk cytogenetics (present or absent)

 Primary endpoint: PFS

 Key secondary endpoints: ORR, OS, DoR, MRD detection, safety

Rodriguez-Otero. NEJM. 2023;388:1002.

2:1

Cyclophosphamide 300 mg/m2 + Fludarabine 30 mg/m2

CAR T-Cell Infusion (Day 0)

Idecabtagene Vicleucel

150-450 x 106 CAR T-cells (n = 254)

Investigators’ Choice SoC* (n = 132)

SOC : DPD(n= 43)

DVd (n = 7)

IRD (n= 22)

Kd (n – 30)

EPD (n= 30)

PD or unacceptable toxicity

*Physician’s choice of PVd or DPd. †As-treated population (n = 176): 32 patients did not receive cilta-cel as part of study due to PD (n = 30) or death (n = 2) during bridging therapy/lymphodepletion.

CARTITUDE-4 (1-3 prior lines of therapy, Cilta-cel vs SOC (DPd or PVd)

Is Early CAR-T A Reality?

ODAC MEETING 3/15/2024

CARVIKTY

• 11-0 in favor of moving up CARVIKTY CAR-T to earlier line of therapy

• There is a safety signal early on (6 patients died due to disease progression, infections i.e COVID19) with CARVIKTY in CARTITUDE

ABECMA –

• 8:3 in favor of moving up ABECMA

• Cross over built in trial design so maybe OS benefit not so seen clearly

What would I do if CAR-T became available earlier?

Be in touch with reality

High risk patients (either with HR cytogenetics/functional high risk) will get early access to CAR-T with first relapse

There has to be a benefit with $$$, Efficacy and Toxicity

The current state where CAR-T and Bispecific therapy is available as 5th line of therapy is not practical as more patients become PI, IMID, mAB refractory at the end of 2-3 LOT

Access will remain an issue

Sequence BCMA-Targeted Therapies

100%

5% 8% sCR CR VGPR PR MR SD PD

Prior BsAb (n = 7) 5% 14% 5% 14% 25% 23% 29% 25% 31% 14%

8. 2

Cohen. Blood. 2023;141:219. Hansen. JCO. 2023;41:2087.

Ide-cel retrospective study: 75% of patients met KarMMa exclusion criteria

ORR: 87% ORR: 73% CR or sCR : 44 %

CR or sCR : 33 %

CR or sCR, MRD-

CR or sCR, MRD+

CR or sCR, MRD unknown

VGPR PR (n = 33) (n = 126)

Best ORR (n=159)

Prior BCMA

Targeted Therapy is an independent predictor of inferior outcomes for response, PFS, and OS

Treatment Landscape in Relapsed MM will change

BCMoreAntige n

CAR-T with non BCMA target in clinical trial

Bispecifics –

CT103

GPRC5D CART

CEVOSTOMA B -FcRH5

CelMODs Iberdomide

Targeted therapy

Belantamab Mafadotin

ddBCMA

DUAL CAR-T

Mezigodomid e

Future of Venetoclax in the t(11;14)

CAR-T cells in RRMM

We NEED more access

Approved CAR-T cells Academi c

Ide-cel KarMMa1 (n = 128)

US. US. China

Cilta-cel CARTITUDE-1 (n = 97) 2,3

CT103A7 (n= 79)

ARI0002h4 (n = 60)

Alternative manufacturin g

P-BCMA-101 PRIME5,6 (n = 53)

Novel Syntheti c AlloCAR GPRC5 D

ddBCMA7 (n= 40)

ALLO-715 UNIVERSAL8 (n = 43)

OriCAR -01790 (n= 13) Phase II Ib/II

CC-952669 (n= 70 )

scFv Chimeric mouse Chimeric Llama Human Humanized Chimeric mouse Synthetic Human Human Humaniz ed Biepitopic

*There, are no head-to-head comparisons of these data and naïve comparison should be conducted with caution

BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; EMD, extramedullary disease; HR cytog, high-risk cytogenetics; NA, not available; NR, not reached/not reported; ScFv, single-chain variable fragment; TCR, T-cell receptor; triple-R, triple-class refractory

1. Anderson L et al. ASCO 2021;abstract;8016 (poster presentation); 2. Berdeja J et al. Lancet 2021;398;314-24; 3. Lin Y et al. EHA 2022;abstract P961 (poster presentation); 4. Fernández de Larrea C, et al. EHA 2022;abstract S103 (oral presentation); 5. Costello C, et al. ASH 2020;abstract 134; 6. Mohyuddin GR et al. Blood Adv 2021;5(4):10971101; 7. Li C et al. EHA 2022;abstract S187 (oral presentation); 7. Li C, et al. ASH 2021;abstract 143; 8. Mailankody S, et al. ASH 2021;abstract 651; 9. Mailankody S, et al NEJM 2022. 10. Zhang et al Lancet Hematology 2023

AO, et al. ASH 2023 Frigault, M, et al. ASH2023. Du J, et al ASH 2023: Abstract 1022: FasT Bal S et al.

Summary:

•Multiple Options available at first relapse

•Nature of relapse, patient and treatment characteristics help decide the appropriate therapy

•In the era of quadruplets, many patients are triple class refractory after 2 nd line of therapy

•Huge gap in terms of effective options after triple class refractory until patient qualify for 5th line approved immunotherapies

•Immune therapy changed MM treatment landscape and eventually, will move from later lines to earlier lines of therapy

•Balance between side effects, $$$, efficacy

•Substantial progress by introducing newer therapies (19 FDA approved drugs in last 20 years, extending lives of patients and we have a long way to in introducing treatment regimens with low toxicity and improved QOL

Thank

EVALUATION

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

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

We greatly appreciate your time and feedback!

Welcome Back

Symptom Management & Living Well with Myeloma

Teresa Miceli, RN, BSN, OCN Mayo Clinic – Rochester, MN

International Myeloma Foundation

Nurse Leadership Board Member

Wintery Mix of Treatment Options Spring into Managing Side Effects Enjoy Life’s Bounty Summer of Success

Wintery Mix of Treatment Options

Diverse and Complex Treatment Combinations

Myeloma Treatment

Velcade® (bortezomib)

Lenalidomide

Common Combinations

DVRd, VRd, Vd

DVRd, VRd, Rd

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

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

Darzalex® (daratumumab)

DVRd, DRd, DVd, DPd, DVMP, DKd

Ninlaro®(ixazomib) IRd

Empliciti® (elotuzumab) ERd, EPd

Xpovio® (Selinexor)

Sarclisa® (Isatuximab)

XVd, XPd, XKd

Isa-Kd, Isa-Pd

Blenrep® (Belantamab mafodotin) Bela-d

Abecma® (Idecabtagene Vicleucel) --

Carvykti™ (ciltacabtagene autoleucel) --

Elrexfio™ (elranatamab) --

Prescribing information. NCCN Guidelines. Multiple Myeloma. V2.2024. Accessed February 5, 2024.

Tecvayli® (teclistamab)

Talvey™ (talquetamab)

Venclexta® (venetoclax)

Vd + ven

New agents or regimens in clinical trials are possible options

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

Stem Cell Transplant

ELIGIBILITY

Measuring Treatment Response

Determining Transplant Eligibility

Insurance Authorization

Collecting Stem Cells

Duration:

Approximately 2 weeks

Location:

Transplant Center

2

TRANSPLANT

High Dose Chemotherapy Stem Cell Infusion Supportive Care Engraftment

Duration: Approximately 3-4 weeks

Location:

Transplant Center

H A S E 3

POSTTRANSPLANT

Restrengthening

Appetite recovery

“Day 100” assessment

Begin maintenance therapy

Duration:

Approximately 10-12 weeks

Location: HOME

Upfront stem cell transplant remains the standard of care for eligible patients

CAR T: Another Treatment Approach

Ask for a referral to CAR Tcell center as soon as it is possible as next treatment option (ie, before relapse)

No driving for 8 weeks

“One & Done” with continued monitoring

T-Cell Collection

Manufacturing takes ≈ 4 to 6 weeks

Bridging therapy may be needed

• Away from home

• Often some hospital stay

• Care Partner needed

• Side effect management

• CRS, ICANS

• Low blood counts

• Fatigue and fever

• Some patients need ongoing transfusion support

Bispecific Antibodies

•Different bispecific antibodies have differences in efficacy, side effects

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

– About 7 in 10 patients respond

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

– CRS and neurotoxicity

– Risk of infection

•BCMA target: greater potential for infection

– Tecvayli® (teclistamab)

– Elrexfio™ (elranatamab)

T cell

BISPECIFIC ANTIBODIES

Cytotoxic cytokines

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

– Talvey™ (talquetamab)

MM cell

Target CD3

Bispecific antibody

MM cell death

BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; GPRC5D = G protein–coupled receptor, class C, group 5, member D; MM = multiple myeloma; scFV = single chain fragment variable. Shah

et

Spring into Managing Side Effects

The Early Bird Gets the Worm:

Communicate Proactively with Your Healthcare Team

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

Unmanaged Myeloma can cause:

• Calcium elevation

• Renal dysfunction

• Low blood counts

• Infection Risk

• Blood clots

• Bone pain

• Neuropathy

• Fatigue

How You Feel

Side Effects of Treatment can cause:

• GI symptoms

• Renal dysfunction

• Low blood counts

• Infection Risk

• Blood clots

• Neuropathy

• Fatigue

Tip: Proactively discuss common side effects with your nurse and what to do if they occur

Tip: Keep a Symptom Diary and bring it to appointments

Infection Can Be Serious for People With Myeloma

[P]reventing infections is paramount

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

IMWG Consensus guidelines and recommendations for infection prevention in multiple myeloma; Lancet Haematol.2022;9(2):143–161.

Infection Prevention Tips

Good personal hygiene (skin, oral)

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

IMWG = International Myeloma Working Group; HCP = healthcare provider. RAJE NS, et al. Lancet Haematol.2022;9(2):143–161. IMF Nurse Leadership Board

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 healthcare team:

Immunizations: Flu, COVID, RSV & and pneumococcal vaccinations; avoid live vaccines

Preventative and/or supportive medications (next slide)

Medications Can Reduce Infection Risk

Type of Infection Risk

Medication Recommendation(s) for Healthcare Team Consideration

Viral: Herpes Simplex (HSV/VZV); CMV Acyclovir prophylaxis

Bacterial: blood, pneumonia, and urinary tract infection

PJP (P. jirovecii pneumonia)

Fungal infections

COVID-19 and Influenza

IgG < 400 mg/dL (general infection risk)

ANC < 1000 cells/μL (general infection risk)

.2022;9(2):143–161.

Consider prophylaxis with levofloxacin

Consider prophylaxis with trimethoprim-sulfamethoxazole

Consider prophylaxis with fluconazole

Antiviral therapy if exposed or positive for covid per institution recommendations

Consider IVIg

Consider GCSF 2 or 3 times/wk (or as frequently as needed) to maintain ANC > 1000 cells/μL and maintain treatment dose intensity

Some people receiving BCMA-targeting therapies have experienced infections that are less common like CMV, PJP and fungal infections

ANC = absolute neutrophil count; BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; CMV, cytomegalovirus; GCSF = granulocyte colony-stimulating factor; HSV = herpes simplex virus; IVIg = intravenous immunoglobulin; PJP = Pneumocystis jirovecii pneumonia; VZV = varicella zoster virus. RAJE NS, et al. Lancet Haematol

Feel Like a Spring Chicken: Prevent and Manage Pain

Pain can significantly compromise quality of life

Sources of pain include bone disease, neuropathy and medical procedures

•Management

– Prevent pain when possible

• Bone strengtheners to decrease fracture risk

• Antiviral to prevent shingles

• Sedation before procedures

– Interventions depend on source of pain

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

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

• Scrambler therapy for neuropathy

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

Peripheral Neuropathy Management

Peripheral neuropathy happens when there is damage to nerves in the extremities (hands, feet, limbs). Damage can be the result of myeloma, treatment or unrelated conditions (i.e. diabetes).

Symptoms:

•Numbness

•Tingling

•Prickling sensations

•Sensitivity to touch

•Burning and/or cold sensation

•Muscle weakness

Prevention / management:

•Bortezomib once-weekly and/or subcutaneous administration

•Massage area with cocoa butter regularly

•Neuroprotective Supplements:

– B-complex vitamins (B1, B6, B12)

– Green tea

•Safe environment: rugs, furnishings, shoes

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

If neuropathy worsens, your provider may:

•Adjust your treatment plan

•Prescribe oral or topical pain medication

•Suggest physical therapy

Understanding Changes to Kidney Function

•Risk Factors

– Active multiple myeloma (light chains, high calcium)

– Other medical issues (ex: Diabetes, dehydration, infection)

– Medications (MM treatment, antibiotics, contrast dye)

– Poor Nutrition

•Prevention

– Stay hydrated – drink water

– Avoid certain medications when possible (eg, NSAIDs), dose adjust as needed

•Treatment

– Treatment for myeloma

– Hydration

– Dialysis

Many myeloma patients will experience kidney issues at some point; protecting your kidney function early and over time is important

Skin Changes: Talvey™ (talquetamab)

Photos: Mount Sinai Hospital, NY, NY

Nurse Leadership Board

Talvey™ (talquetamab): Common But Generally Mild and Painless Skin and Nail Side Effects

Body Rash:

Prevent dry skin; apply lotion

• Ammonium lactate 12% lotion

Steroids:

• Topical for grades 1-2,

• Systemic and topical for Grade 3 and dose hold

• Antihistamines, as needed

.

Nail Changes:

•Keep your nails short and clean. Watch for “catching and tearing”

Photos: Mount Sinai Hospital, NY, NY Nurse Leadership Board

•Apply a heavy moisturizer like Vaseline or salve. Wear cotton hand coverings to bed

•A nail hardener may help with thinning

•Tell the team if you have signs of a fungal infection, like thickened or discolored nails

Management of Talvey™ (talquetamab):

Oral Toxicities

Taste Changes

Dexamethasone oral solutions

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

Glossitis and thrush

EARLY initiation of nystatin or Mycelex is key to manage symptoms.

Dry Mouth

OTC dry mouth rinse, gel, spray are recommended. Advise patients to avoid hot beverages.

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

• Weight loss and anorexia are associated with taste changes. Nutritionist involvement and dietary modifications are recommended to support patients. Appetite stimulant with Marinol, if indicated, can also be utilized.

• Education and emotional support are key strategies to manage oral toxicities.

GI Symptoms: Prevention & Management

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

Diarrhea may be caused by medications and supplements

•Laxatives, antacids with magnesium

•Antibiotics, antidepressants, other (check with provider, pharmacist)

•Supplements: milk thistle, aloe, cayenne, saw palmetto, ginseng

Avoid caffeinated, carbonated, or heavily sugared beverages

Take anti-diarrheal medication if recommended

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

Constipation may be caused by medications and supplements

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

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

Increase fiber

•Fruits, vegetables, high fiber whole grain foods

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

Weight Management

Anorexia (difficulty eating)  Weight loss; Steroids  Weight gain

– Monitor weight for significant loss or gain

– Adjust diet (reduce calories or add supplements )

Side Effects

Confusion

Weakness

Fever

Diarrhea

Cytokine Release Syndrome

Fatigue

Headache

Nausea / vomiting

Shortness of Breath

CRS is a common but often mild & manageable side effect

Unique Side Effects

Neurotoxicity is a rare but serious side effect

Headache

Encephalopathy

Seizures

Confusion

NEUROTOXI

CITY

Tremors

Facial nerve palsy

Apraxia

Altered wakefulness

Ataxia

Hallucinations

Are Steroids Messing With Your Sunny Disposition?

Steroids enhance the effectiveness of other myeloma therapies

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

• Irritability, mood swings, depression

Steroid Side Effects

• Difficulty sleeping (insomnia), fatigue

Managing Steroid Side Effects

•Consistent schedule (AM vs. PM)

•Take with food

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

•Medications to prevent shingles, thrush, or other infections

• Blurred vision, cataracts

• Flushing/sweating

• Increased risk of infections, heart disease

• Muscle weakness, cramping

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

• Weight gain, hair thinning/loss, skin rashes

• Increased blood pressure, water retention

• Increased blood sugar levels, diabetes

Don’t Hibernate Through Spring

98.8%

Fatigue

Fatigue is the most commonly reported symptom.

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

Anxiety

>35% of patients

Depression

≈25% of patients

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

Additional Supportive Care

Supportive Medications

DVT/PE

Prevention

Blood thinners

Ex: Aspirin, DOACs

Bone Health

Bone Strengthening Agents

Calcium

Vitamin D

Fatigue

Stimulant medications

Red Cell Transfusion (anemia)

Non-medication

Therapies

Compression stockings

Radiation Surgery

Immobilization

Physical therapy

Relaxation

Meditation

Activity

Lifestyle Options

Stop smoking

Weight loss

Anxiety

Anti-depressants

Anti-anxiety

Therapy

Relaxation

Meditation

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.

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

Funding and assistance may be available

Federal programs, IRA & Medicare “Extra Help”

Pharmaceutical support

Non-profit organizations

– Websites:

• Medicare.gov

• SSA.gov

• LLS.org

• Rxassist.org

• NeedyMeds.com

• HealthWellFoundation.org

• Company-specific website

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

Summer of Success

Care Partners Are Vital for Success

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

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

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

•Caring for the Care Partner

– Recognize that caregiving is difficult/stressful

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

– The IMF has information and resources to help care partners

African Proverb

Cultivate Strong Social Ties & Belonging

Multiple studies demonstrate that strong social ties are associated with

 Increased longevity including people with cancer

 Improved adherence to medical treatment leading to improved health outcomes

 Lower risk of developing cardiovascular diseases

 Increased sense of purpose and life satisfaction

 Reduced stress and anxiety

 Improved mood and happiness

 Enhanced resilience

Martino J, et al. Am J of Lifestyle Med. 2015;11(6):466-475.

Yang YC, et al. Proc Natl Acad Sci U S A. 2016;113(3):578-583.

Pinquart M and Duberstein PR. Crit Rev Oncol Hematol. 2010; 75(2):122–137.

Strategies

for enhancing social connection

 Deepen existing relationships with family, friends, and loved ones

 Build new relationships by participating in a support group, joining clubs or organizations, or volunteering

Tip: Start with small steps outside your comfort zone. Call a loved one you haven’t spoken to in a while. Invite a person you’d like to know better for lunch, coffee, or a walk.

Hetherington C. Healthnews.

https://healthnews.com/longevity/healthspan/social-connection-andlongevity/#:~:text=Research%20consistently%20demonstrates%20that %20people,of%20fulfillment%20in%20your%20life. Accessed

Defining Your Success

Discuss your goals and priorities with your healthcare team

Myeloma Therapies

 Rapid and effective disease control

 Durable disease control

 Improved overall survival

 Minimize side effects

 Promote good quality of life

Supportive Treatment

 Prevent disease- and treatmentrelated side effects

 Optimize symptom management

 Promote quality of life

Enjoy Life’s Bounty

Harvest Good Health

Have a Primary Care Doctor

Have Recommended Health Screenings

• Blood pressure

• Cholesterol

• Cardiovascular disease

• Diabetes

• Colonoscopy

• Vision

• Hearing

• Dental checkups & cleaning

• Women specific: mammography, pap smear

• Men specific: prostate

Maintain a healthy weight

• Good nutrition

• Activity or exercise

• Sufficient Sleep (next slide)

An ounce of prevention is worth a pound of cure.

Benjamin Franklin

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-56.

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

Plentiful Sleep: Important for Good Health

Adequate rest and sleep are essential to a healthful lifestyle

Shortened and disturbed sleep cause

– Increased heart-related death

– Increased anxiety

– Weakened immune system

– Worsened pain

– Increased falls and personal injury

Things that can interfere with sleep

– Medications: steroids, stimulants, herbal supplements

– Psychologic: fear, anxiety, stress

– Physiologic: sleep apnea, heart issues, pain

Sleep hygiene is necessary for quality nighttime sleep and daytime alertness

– Engage in exercise but not too near bedtime

– Increase daytime natural light exposure

– Avoid daytime napping

– Establish a bedtime routine - warm bath, cup of warm milk or tea

Associate your bed ONLY with sleep

– Avoid before bedtime:

• Caffeine, nicotine, alcohol and sugar

• Large meals and especially spicy, greasy foods

• Computer screen time

Sleep aid may be needed

Rod NH et al 2014. PloS one. 9(4):e91965; Coleman et al. 2011. Cancer Nurs. 34(3):219-227.National Sleep Foundation. At: http://sleepfoundation.org/ask-the-expert/sleep-hygiene Mustian et al. Journal of clinical Oncology. Sep 10 2013;31(26):3233-3241; Stan DL, et al. Clin J Oncol Nurs. Apr 2012;16(2):131-141; Zeng Y et al., Complementary therapies in medicine. Feb 2014;22(1):173-186.

EVALUATION

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

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

We greatly appreciate your time and feedback!

Health Disparities in Myeloma

Patient and Family Seminars

Joseph Mikhael MD, MEd, FRCPC

Chief Medical Officer, International Myeloma Foundation

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

What are Health Disparities?

•Health disparities are preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations - Centers for Disease Control (CDC)

•Health equity generally refers to individuals achieving their highest level of health through the elimination of disparities in health and health care

What are the DRIVERS of Disparities in MM?

1. Systemic racism

2. The Healthcare system

3. Social Determinants of Health

4. Biology of the disease and concomitant comorbidities

5. Delayed Diagnosis

6. Access to Care – Triplets, Transplants, Trials and Car T

7. Lack of diversity, cultural sensitivity and optimal communication in healthcare professionals

A Call to Action Facts About African Americans and Myeloma

1.There is a longer time from symptoms to diagnosis among African Americans

2.African Americans and Latino Americans are younger by about 5-6 years on average at diagnosis

3.MM and MGUS are more than 2x as common in African Americans

4.African Americans and Latino Americansare less likely to receive the FOUR T’s: Transplant, Triplets, Trials and CAR Ts

5.African Americans have biologic differences with more t(11;14) and less high-risk cytogenetics with deletion 17p

6.Survival outcomes in African Americans are HALF of what is seen in White Americans

7.African Americans can achieve equal or better outcomes when they receive therapy

What are the DRIVERS of Disparities in MM?

1. Systemic racism

2. The Healthcare system

3. Social Determinants of Health

4. Biology of the disease and concomitant comorbidities

5. Delayed Diagnosis

6. Access to Care – Triplets, Transplants, Trials and CART

7. Lack of diversity, cultural sensitivity and optimal communication in healthcare professionals

M-Power = Myeloma Power

The core vision of this initiative is to improve the short- and longterm outcomes of African American patients with myeloma. We want to empower patients and communities to change the course of myeloma…

ENHANCE

ENGAGE

M-Power

Engage the community to increase awareness and provide support

Enhance access to optimal care by educating myeloma providers about the disparity and how to reduce it

EDUCATE

Shorten the time to diagnosis by educating primary care providers to recognize the disease and order the right tests

M-Power Is Both a National and Local Movement

Local Efforts

National Efforts

2023 M-Power Community Workshops

April 1, 2023

50+ attended

81% African American

• 100% rated v good or excellent

• 100% learned something new!

June 17, 2023

50+ attended

68% African American

• 80% at the Grace Baptist Church learned of the Workshop through their congregation

• 63% at the Riverside Church location learned of the Workshop from IMF

September 24, 2023

35+ attended

41% African American

• 96% of attendees rated the program as excellent

• 92% of the attendees reported learning something new

November 4, 2023

75+ attended

61% African American

• 100% plan to share something they learned

• 76% had not previously attended an IMF program

Facebook Live

Education of Primary Care Providers

Our goal is to reduce DELAYS in diagnosis among African Americans by educating the primary care community with a focus on:

• Recognizing the signs and symptoms of myeloma

• Discriminating myeloma from other diagnoses such as diabetes

• Capturing an accurate diagnosis through proper use of testing

• Providing referral guidelines for Hematology and Oncology

• Grand Rounds

• Postcards mailed to 6,000+ PCPs in target cities

• Free PCP CME course “Don’t Miss Myeloma”

• Cobb Institute talk

• Talk at NMA Annual Meeting

• Articles and pending publications

8,000 Learner s

Annual Meeting of the National Medical Association

Jane Cooke Wright Symposium on Health

Disparities

• Hosted by Dr. Edith Mitchell

• Keynote speaker - Dr. Monica Bertagnolli, the director of the National Cancer Institute (NCI)

• Dr. Mikhael spoke about health disparities in myeloma

Poster Walk

Student research was presented to Yelak Biru, Dr. Mikhael, Dr. Mitchell, Dr. Morgan (CEO of the Cobb Institute) and Dr. Bertagnolli.

M-Power Website:

•Web Stats: Over 40k Page views across main, city sites & myeloma.org

•Google PPC targeted web traffic

Email Stats:

•Total Sent: 18 emails

•Total Audience: 38k*

•Open Rate Avg: 31%*

*Note: We have continued to refine lists, contributing to a more engaged audience as evidenced in the Open Rates (The industry standard high-mark is 21%).

M-Minute Promotion

Stats:

•Total Sent: 19 emails

•Total Audience: 323k

•Open Rate Avg: 38.91%

M-Power Related Video

Stats:

• Total Views: Over 50k

Future Direction

Engage

• Planning for 2024 workshops in New York (Juneteenth) and other cities

• Expand online and social media strategy

sEducate

• Primary care program in Charlotte

• Lab based education

• Electronic Medical Record Initiative

Enhance

• Rolling out the Clinical Trial Mentor (CTM) as part of the Diversity in Clinical Trials initiative

• Nurse equity decision tool

Conclusions

•Health disparities are sadly prevalent across all diseases, but particularly in multiple myeloma

•There are MANY other types of inequity in myeloma, including geography, age, gender, orientation…

•Being aware of these disparities is critical to overcoming them

•The IMF’s M-Power is designed to reduce the inequity with specific emphasis on delayed diagnosis, access to therapy and diversity sensitive clinical care

What Can I Do??

•Be more conscious of the topics of health equity

•Evaluate the opportunities in your experience to reduce disparities

•Support the M-Power movement!

mpower.myeloma.org

EVALUATION

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

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

We greatly appreciate your time and feedback!

LUNCH

Breakout Sessions #2: Patients and Care Partners

Patients Only – Lessons Learned

Yelak Biru

Grand Oasis Ballroom

Care Partners Only

Nancy Bruno & Teresa Miceli

Royal Palms

Patients Only – Lessons Learned

Yelak Biru

Patient, President, CEO

International Myeloma Foundation

Bone Health in Multiple Myeloma

Matthew Drake, MD, PhD

Mayo Clinic

Rochester, MN

BONE HEALTH IN MULTIPLE MYELOMA

Matthew T. Drake, MD, Ph.D

Mayo Clinic College of Medicine

Boca Raton, Florida

March 16, 2024

Learning Objectives

Describe the physiologic/molecular bases for myeloma bone disease

Define how treatment with a bisphosphonate differs from treatment with denosumab and the potential for subsequent fracture risk with therapy discontinuation

Recognize the skeletal significance of MGUS

SKELETAL LESIONS IN MYELOMA

80-90% of patients with myeloma have bone involvement

• Spine, ribs, pelvis, skull, femur, humerus

Severe Features

• Intractable pain

• Increased fracture risk

• Hypercalcemia (high blood calcium)

• Risk for nerve compression

Also generalized bone loss (osteoporosis)

SITE-SPECIFIC FRACTURE RISK IN MYELOMA

SIGNIFICANT FACTORS FOR INCREASED RISK OF DEATH IN MULTIPLE MYELOMA

MYELOMA BONE DISEASE

Myeloma cells

Tumor-derived osteoclast activating factors

• Macrophage inflammatory protein-1 alpha

• Interleukin-3

Stromal cells

Osteoclast

Tumor-derived osteoblast inhibitory factors

• Dickkopf1 (DKK1)

• IL-3

• sFRP2

• IL-7 Bone

Osteoblasts

MYELOMA CELLS DISRUPT BONE REMODELING

Bone Resorption

Bone Formation

CLINICAL CONSEQUENCES OF MYELOMA BONE

DISEASE

•Pathological fractures

• Non-vertebral

• Vertebral compression

•Spinal cord compression/collapse

•Radiation therapy

•Surgery to bone

•Hypercalcemia

•Bone pain

•Use of analgesics

•Quality-of-life

*SREs

*SREs- skeletal-related events

PHARMACOLOGIC MANAGEMENT OF MYELOMA BONE DISEASE

•Current recommendations

- Pamidronate (Aredia) 90 mg/monthly (or less often)

- Zoledronate (Zometa) 4 mg/monthly (or less often)

- Denosumab (Xgeva) 120 mg/monthly

•Anti-resorptives improve skeletal outcomes

- Bone pain - Hypercalcemia - Fractures

BISPHOSPHONATES TARGET MATURE OSTEOCLASTS

Normal Osteoclast Bisphosphonatetreated

Apoptotic osteoclast

SKELETAL RELATED EVENT RISK –

ZOLEDRONATE VS PAMIDRONATE

Zoledronat

Pamidronat

DENOSUMAB (XGEVA) INHIBITS OSTEOCLAST FORMATION

Osteoclas t

Precursor

Activated Osteoclast

RANK Ligand RAN K

Denosuma

Osteoblas

PRIMARY ENDPOINT: NON-INFERIORITY FOR TIME TO FIRST ON-STUDY SKELETAL RELATED EVENT

HR (95% CI) = 0.98 (0.85, 1.14); P=0.01 (Noninferiority)

DENOSUMAB (XGEVA) THERAPY CONSIDERATIONS

Denosumab does not cause osteoclast apoptosis like bisphosphonates; rather it prevents pre-osteoclasts from becoming active osteoclasts.

Therefore, any treatment with denosumab must be followed by a bisphosphonate (such as zoledronate) to limit rebound bone resorption.

The timing of bisphosphonate treatment relative to the last dose of denosumab is not clear.

RANKL is not specific to osteoclasts but has a role in the regulation of other immune cells. This may explain the slightly increased rates of infection in denosumab-treated patients.

Denosumab may be a good option in patients with kidney dysfunction

Multiple Myeloma without bone lesions

Limited data exists on the routine use of bisphosphonates in myeloma patients without osteolytic disease

Data from the MRC IX Trial showed that myeloma patients without bone lesions at baseline who received zoledronate had fewer skeletal related events compared to patients treated with clodronate

Guidelines from the European Myeloma Network suggest that patients with symptomatic patients but without lytic lesions can be treated with zoledronate based on this data

Morgan

BONE LOSS ALSO OCCURS IN MGUS

•MGUS is a common pre-malignant condition with an ~ 1% annual risk of progression to MM

•MGUS prevalence increases with age and affects ~ 3.4 million Americans

• 3.2% adults aged > 50 years

• 7.5% adults aged > 85 years

Kyle et al. (2006) NEJM 354:1363; Melton et al. (2004) J Bone Miner Res. 19:25.

FRACTURE RISK IS INCREASED IN MGUS

F o l d i n c r e a s e d f r a c t u r e r i s k

Femu r Any Axial Vertebra l

MGUS Patients have Decreased Volumetric Bone Mineral Density and Microstructure

Bisphosphonate Use in MGUS

Alendronate (70 mg/weekly) ↑ bone density at the spine and hip in osteoporotic MGUS patients

Zoledronic acid (4 mg/every 6 months) ↑ bone density at the spine and hip in MGUS patients with osteopenia/osteoporosis

Neither study was large enough to evaluate for fractures, although fractures generally follow bone density results

Treatment of the MGUS Patient

Patients with MGUS are at increased fracture risk

A pro-active approach is warranted

– May include DXA, counseling on fall risks, lifting recommendations, ensuring adequate calcium and vitamin D intake

In patients with documented osteoporosis (by DXA, history of a fragility fracture, height loss, or kyphosis), medical intervention with anti-resorptive therapy (such as a bisphosphonate) is warranted

In patients with osteopenia, medical therapy to limit bone loss and fracture risk may be appropriate and must be considered carefully

UPDATED IMAGING GUIDELINES IN MONOCLONAL PLASMA CELL DISORDERS

•Optimal imaging supports clinical care decisions

•Bone disease supports the immediate start of systemic therapy

•Imaging can identify painful bone lesions or skeletal sites at increased risk for pathologic fractures or neurologic complications (spinal cord compression)

QUESTIONS

EVALUATION

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

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

We greatly appreciate your time and feedback!

Ask – the – Experts Panel

Led by Dr. Joseph Mikhael

Guest Faculty:

Peter Voorhees, MD

Gurbakhash Kaur, MD

Teresa Miceli, RN, BSN, OCN

Matthew Drake, MD, PhD

EVALUATION

Thank you for joining us today! Please take a moment to complete your program evaluation form. Our team members will collect these from you on your way out.

We greatly appreciate your time and feedback!