2nd M-Power Charlotte Community Workshop

Community Workshop June 25th, 2022

The 2nd M-POWER CHARLOTTE WORKSHOP: CHANGING THE COURSE OF MYELOMA

10AM ET

THANK YOU TO OUR SPONSOR!

Welcome and Speaker Introductions Joseph Mikhael MD, MEd, FRCPC, FACP Chief Medical Officer, IMF

Today’s Presenters

Dr. Joseph Mikhael Chief Medical Officer International Myeloma Foundation

Yelak Biru, MSc Tiffany W. Crank, MPH Amy E. Pierre, President and CEO, Community Outreach Mgr RN, MSN, ANP-BC International Myeloma Levine Cancer Institute Memorial Sloan Kettering Foundation Charlotte, NC Cancer Center Flatiron Health New York, NY

Robert Pugh Patient, Pastor, and Entrepreneur Charlotte, NC

Dr. Peter Voorhees Myeloma Specialist Levine Cancer Institute Charlotte, NC

8

M-POWER CHARLOTTE COMMUNITY WORKSHOP Saturday June 25, 2022 ~ Agenda

Welcome & Speaker Introductions Changing the Course of Myeloma in Charlotte

Race Matters in Myeloma Care & Survival

Dr. Joseph Mikhael, International Myeloma Foundation

A Conversation with IMF President and CEO, Yelak Biru

Communicating with your Healthcare Team: A 2-Way Street

Dr. Joseph Mikhael, International Myeloma Foundation

Myeloma for Patients Who Are Just Getting Started Dr. Joseph Mikhael, International Myeloma Foundation

Building Bridges: Connecting with the Community An interview with Tiffany W. Crank, MPH, Levine Cancer Institute

When Myeloma Comes Back

Dr. Peter Voorhees, Levine Cancer Institute

Audience Questions

Amy Pierre

Break 15 minutes

An Interview with Local Patient and Pastor, Robert Pugh Audience Questions Closing and Survey

Dr. Joseph Mikhael, International Myeloma Foundation

Race Matters in Myeloma Care and Survival Joseph Mikhael MD, MEd, FRCPC, FACP Chief Medical Officer, IMF

1. Myeloma is the most common blood cancer in African Americans And the incidence is growing….

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

2. 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.

3. African Americans are younger at diagnosis by about 5 years Hispanic

African American

Asian

White

65

66

69

71

YEARS

YEARS

YEARS

The median age at diagnosis for all patients is 69 years

YEARS

4. African Americans comprise about 20% of all patients with MM Currently, African Americans comprise 14% of the total population of the USA

5. African Americans have only HALF the survival of White Americans We have made huge progress in survival in MM but this has not been realized to the same extent in African Americans

6. There is a LONGER time from symptom onset to diagnosis in African Americans The average myeloma patient sees their primary care doctor THREE times with symptoms and signs consistent with MM. The delay is even longer in African Americans, for many reasons: Confounding diagnoses (like diabetes) Access to diagnostics and care Awareness in primary care providers Timely referral to specialists…

7. African Americans are less likely to receive the critical treatments for MM – The 3 Ts: Triplets, Transplants, and CAR T cell therapy

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

8. African Americans are much less likely to participate in Clinical Trials (the 4th T)

9. There are biologic differences in African Americans with MM that may lead to lower risk disease African ancestry associated with less aggressive disease Higher prevalence of [a]: t(11;14) t(14;16) 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.

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

Fillmore NR, et al. Blood. 2019;133:2615-2618

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 • We believe the IMF is uniquely poised to address this issue and bring many of these key stakeholders together…

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.

M-Power = Myeloma Power We want to empower patients and communities to CHANGE the current course of myeloma • Increase Awareness • Reduce Stigma • Shorten the time to diagnosis • Educate providers about culturally competent care 23

A Conversation with IMF President and CEO, Yelak Biru Joseph Mikhael MD, MEd, FRCPC, FACP Chief Medical Officer, IMF

Myeloma for Patients Who Are Just Getting Started Joseph Mikhael, MD, MEd, FRCPC, FACP 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”

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 of the plasma cells of that live in the bone marrow – Plasma Cells normally make antibodies to help us fight infections – Myeloma cells are abnormal plasma cells that make an abnormal antibody called “M protein” – The M stands for “monoclonal” = “identical” * 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

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

Trends in MM Natural History by Race MM  Higher incidence in AA vs White patients: Incidence • 15.9 vs 7.5 cases per 100,000 per year

MM  Higher mortality in AA vs White patients: Mortality • 5.6 vs 2.4 MM deaths per 100,000

MYELOMA IS A CANCER OF PLASMA CELLS •

Cancer of plasma cells

•

Healthy plasma cells produce antibodies or “immunoglobulins” G, A, M, D, and E

•

Myeloma cells produce abnormal 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, 70 years)

Bone marrow of patient with multiple myeloma Image courtesy of American Society of Hematology Kyle et al. Mayo Clin Proc. 2003;78:21-33;

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

MULTIPLE MYELOMA DIAGNOSIS CAN BE CHALLENGING

Fatigue

Bone Pain Kyle RA. Mayo Clin Proc.

2003;78:21-33.

Anemia

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

BM

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

Weakness Fatigue Infection Weakness

Bone Damage • Affects 85% of patients • Leads to fractures

Bone pain

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

Loss of Appetite & Weight loss

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

35

MULTIPLE MYELOMA TYPICALLY PRECEDED BY PREMALIGNANT CONDITIONS Premalignant

Condition Clonal plasma cells in bone marrow Presence of Myeloma Defining Events Likelihood of progression Treatment

Malignant

(Monoclonal Gammopathy of Undetermined Significance)

SMM1-5,8

(Smoldering Multiple Myeloma)

Active Multiple Myeloma6-8

<10%

10%-60%

>10%

None

None

Yes

~1% per year

~10% per year

Not Applicable

No; observation

Yes for high risk*; No for others

Yes

MGUS1-4

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):62-69.

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.

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

TOOLS OF THE TRADE FOR FRONTLINE THERAPY STANDARD DRUG OVERVIEW

Class

Drug Name IMiD immunomodulatory drug

Abbreviation

Revlimid (lenalidomide)

R or Rev

Thalomid (thalidomide)

T or Thal

Chemotherapy Steroids Monoclonal Antibodies

Oral

Kyprolis (carfilzomib)

C or K or Car

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

Ninlaro (ixazomib)

N or I

Oral

Cytoxan (cyclophosphamide)

C

Alkeran or Evomela (melphalan)

M or Mel

Decadron (dexamethasone)

Dex or D or d

Prednisone

P

Daratumumab (Darzalex) Istuximab (Sarclisa)

Dara Isa

Velcade (bortezomib) Proteasome inhibitor

V or Vel or B

Administration

Oral or intravenous Oral or intravenous Intravenous (IV) or subcutaneous (SQ)

GENERAL PRINCIPLES OF INITIAL THERAPY 1. Most patients will be given a combination of drugs to control the disease quickly 2. We don’t “save the best for last” because early therapies have a long term effect on survival 3. We seek a DEEP and DURABLE response 4. We mix and match from the 3 major classes of drugs and add steroids: Proteasome Inhibitors – most often botezomib (Velcade) Immunomodulatory Drugs – lenalidomide (Revlimid) Monoclonal Antibodies – daratumumab (Darzalex) 5. 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

RAJKUMAR SV. 2020

Treatment Algorithm in Frontline Newly Diagnosed MM

Not Transplant Candidate

VRd x 8-12 cycles followed by Len

Transplant Candidate VRd x 4 cycles

DRd

Early Auto SCT followed by Maintenance

*Based on CALGB 100104, S0777, IFM-2009, MAIA ¶ VTd/VCd if VRd not available

Collect & store Continue VRd x4 Maintenance Delayed Transplant

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…

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

THE EVOLUTION OF MYELOMA THERAPY

Now

VD Rev/Dex CyBorD VTD VRD SCT KRD Tandem ASCT (?)

D-VMP DRD Front line treatment

Induction

New

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

Nothing Thalidomide?

Bortezomib Ixazomib Lenalidomide Combinations Maintenance

Consolidation

Post consolidation

“more” induction?

Daratumumab?

Carfilzomib?

Lenalidomide + PI

ASCT, autologous stem cell transplant; CAR, chimeric antigen receptor; Cy, cyclophosphamide; d- daratumumab; D/dex, dexamethasone; isa, isatuximab; K, carfilzomib; M, melphalan; PD-L1, programmed death ligand-1; PI, proteasome inhibitor; Rev, lenalidomide; V, bortezomib. Speaker’s own opinions.

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

Rescue

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, FACP 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

Building Bridges: Connecting with the Community An interview with Tiffany W. Crank, MPH, Levine Cancer Institute Joseph Mikhael MD, MEd, FRCPC, FACP Chief Medical Officer, IMF

When Myeloma Comes Back Peter Voorhees, M.D. Professor of Medicine Chief, Plasma Cell Disorders Division Associate Medical Director for Clinical Trials Vice Chair of Clinical Operations Department of Hematologic Oncology and Blood Disorders Levine Cancer Institute, Atrium Health / Wake Forest Baptist

CASE The patient is a 67-year-old Black man with IgG lambda multiple myeloma. The patient had ISS stage 2 disease and an (11;14) translocation at original diagnosis. Past medical history included diabetes and hypertension. He received 4 cycles of lenalidomide, bortezomib and dexamethasone induction therapy followed by high dose melphalan / autologous stem cell transplantation to which he achieved a complete response. Treatment was complicated by bortezomib-induced neuropathy with pain. Three months after transplant, he started lenalidomide maintenance therapy and continues it to this day. Aside from low grade fatigue and intermittent diarrhea and muscle cramps, he has done well with therapy and is able to live his life with minimal impact on quality of life. His bortezomib-induced neuropathy is well controlled but there is residual numbness and tingling in the feet for which the patient takes duloxetine.

He now presents with worsening low back pain, and his M spike has risen from undetectable to 1.1 g/dL. Plain x-rays of the spine are unremarkable, but an MRI reveals a new lytic lesion with soft tissue extension at the level of L3.

What to do next?

DOC, AM I IN REMISSION? National Cancer Institute Dictionary of Cancer Terms: •

Progressive Disease: Cancer that is growing, spreading, or getting worse.

•

Relapse: The return of a disease or the signs and symptoms of a disease after a period of improvement.

Disease progression / progressive disease, disease coming out of remission, and relapse are used interchangeably. In all cases, it means that the myeloma cells are growing and dividing, and the burden of disease is increasing. https://www.cancer.gov/publications/dictionaries/cancer-terms/

IDENTIFYING RELAPSE •

Blood and urine studies • Regular SPEP and serum free light chain testing •

•

Serum free light chain can replace 24-hour urine testing in many cases

Free light chain escape When myeloma cells stop making the heavy chain and just make the light chain part of the antibody • e.g. IgA kappa myeloma changes into free kappa light chain myeloma • Picked up by serum free light chain testing.

•

•

Non-secretory and oligo-secretory myeloma.

The myeloma cells lose the ability to make any antibody or make minimal antibody • Not measurable by SPEP and serum free light chains •

•

More frequent imaging and bone marrow biopsies required to track the myeloma

IDENTIFYING RELAPSE • Imaging • Bone Imaging • Skeletal survey • Low dose CT • CT, MRI, whole body PET-CT • Monitoring for disease outside of the bones (extra-medullary multiple myeloma) • PET-CT, CT, MRI • Clinical symptoms • New, progressive bone pain • Worsening fatigue

NCCN GUIDELINES FOR RELAPSED MULTIPLE MYELOMA: 1 – 3 PRIOR THERAPIES Preferred Regimens

Level of Evidence

Lenalidomide, carfilzomib, dex

1

Lenalidomide, elotuzumab, dex

1

Lenalidomide, ixazomib, dex

1

Lenalidomide, daratumumab, dex

1

Lenalidomide, bortezomib, dex Carfilzomib, daratumumab, dex

1

Carfilzomib, isatuximab, dex

1

Pomalidomide, daratumumab, dex

1

Pomalidomide, isatuximab, dex

1

Pomalidomide, bortezomib, dex

1

Pomalidomide, ixazomib, dex

11 preferred regimens, 15 other recommended regimens, 15 regimens useful in certain circumstances = 41 regimens

How to decide?!?!?

Accessed April 2022

PABST: THE BLUE RIBBON APPROACH TO TREATMENT OF RELAPSED MULTIPLE MYELOMA •

Past medical history •

•

What co-morbidities will impact tolerability of therapy?

Adverse events •

What toxicities were experienced with prior therapy?

•

Biochemical vs clinical relapse/progression

•

Standard vs high-risk disease biology

•

Treatment history •

Is the disease resistant to specific drug classes?

• • •

Carfilzomib refractory = bortezomib and ixazomib refractory Pomalidomide refractory = lenalidomide refractory Daratumumab refractory = isatuximab refractory

BACK TO OUR PATIENT • • •

• •

Past medical history: 1) Diabetes – cautiously dosed dex and get rid of it quickly; 2) Hypertension – carfilzomib ok but monitor for worsening.

Adverse events: Prior history of bortezomib-induced neuropathy with pain – avoid bortezomib-based therapy at relapse.

Biochemical vs clinical relapse: This patient has clinical relapse with increasing pain and a new bone lesions – we need to use a therapy with a high likelihood of success and deep response.

Standard vs high risk: This patient has standard risk disease – no issues.

Treatment History: The patient has disease that has progressed on lenalidomide – avoid the use of a lenalidomide-based regimen

NCCN GUIDELINES FOR RELAPSED MULTIPLE MYELOMA: 1 – 3 PRIOR THERAPIES Preferred Regimens

Level of Evidence

Lenalidomide, carfilzomib, dex

1

Lenalidomide, elotuzumab, dex

1

Lenalidomide, ixazomib, dex

1

Lenalidomide, daratumumab, dex

1

Lenalidomide, bortezomib, dex Carfilzomib, daratumumab, dex

1

Carfilzomib, isatuximab, dex

1

Pomalidomide, daratumumab, dex

1

Pomalidomide, isatuximab, dex

1

Pomalidomide, bortezomib, dex

1

Pomalidomide, ixazomib, dex

11 preferred regimens, 15 other recommended regimens, 15 regimens useful in certain circumstances = 41 regimens

How to decide?!?!?

Accessed April 2022

CD38 MONOCLONAL ANTIBODIES WITH CARFILZOMIB OR POMALIDOMIDE IN RELAPSED MYELOMA Carfilzomib

Daratumumab

Isatuximab

Pomalidomide

The addition of CD38 antibodies to pomalidomide and carfilzomib reduce the risk of myeloma progression and death by 37% - 47% Attal, M, et al. Lancet 2019;394:2096 - 2107 Dimopoulos, M, et al. Lancet Oncol 2021;22:801-812

Moreau, P, et al. Lancet 2021;397:2361 - 2371 Usmani S, et al. Lancet Oncol 2022;23:65-76

BACK TO OUR PATIENT After a discussion with their physician, the patient chooses subcutaneous daratumumab with pomalidomide and dexamethasone. He achieves a very good partial response within 4 cycles of treatment start. Two and a half years into treatment, the patient experiences new right hip pain. The M spike remains at its nadir of 0.1 g/dL. However, the serum free lambda light chain level has increased from a nadir of 24.6 mg/L to 112.2 mg/L. An MRI of the hip reveals an impending fracture of the right hip for which the patient undergoes a total hip replacement.

After recovery, what to do next?

BACK TO OUR PATIENT •

Past medical history: 1) Diabetes – cautiously dosed dex and get rid of it quickly; 2) Hypertension – carfilzomib ok but monitor for worsening.

•

Adverse events: Prior history of bortezomib-induced neuropathy with pain – avoid bortezomib-based therapy at relapse.

•

Biochemical vs clinical relapse: This patient has clinical relapse with increasing pain and a new bone lesion – we need to use a therapy with a high likelihood of success and deep response.

•

Standard vs high risk: This patient has standard risk disease with unique disease biology [t(11;14)].

•

Treatment History: The patient has disease that has progressed on lenalidomide, pomalidomide and daratumumab – avoid the use of an IMID (len/pom) or CD38 antibody (daratumumab, isatuximab)based treatment.

BELLINI: OUTCOMES IN T(11;14)+ MULTIPLE MYELOMA WITH VENETOCLAX, BORTEZOMIB AND DEXAMETHASONE Investigator-Assessed PFS in Patients With t(11;14) PFS Median, months HR (95% CI) P value

Kumar, S et al. ASH 2021.

Ven + Bd Pbo + Bd 36.8 9.3 0.12 (0.03–0.44) .0014

OS in Patients With t(11;14) OS Events Median, months HR (95% CI) P value

Ven + Bd Pbo + Bd 4 5 NR NR 0.61 (0.16–2.32) .4654

BACK TO OUR PATIENT The patient chooses to participate in a phase I/II clinical trial with venetoclax, carfilzomib and dexamethasone and achieves an MRD negative complete response. He requires the addition of a second blood pressure medication to his regimen to control his blood pressure but is otherwise doing well. Three years later, his M spike has risen to 0.5 g/dL from undetectable and serum free lambda light chains from 3.6 mg/L to 46.4 mg/L. He has no new symptoms and imaging reveals no new or larger bone lesions. His bone marrow shows 10% myeloma cells, up from undetectable.

What to do next?

NCCN GUIDELINES FOR RELAPSED MULTIPLE MYELOMA: ≥4 PRIOR THERAPIES Regimens Selinexor, dex Belantamab mafodotin Idecabtagane Vicleucel Ciltacabtagene Autoleucel

Accessed April 2022

Level of Evidence

BACK TO OUR PATIENT • • • • •

Past medical history: 1) Diabetes – no more dex!!! 2) Hypertension Adverse events: Not as important as we are looking at completely new therapy.

Biochemical vs clinical relapse: This patient has biochemical progression which affords more flexibility about new treatment start.

Standard vs high risk: There is no such thing as standard risk disease in this circumstance.

Treatment History: The patient has disease that has progressed on lenalidomide, pomalidomide, daratumumab, carfilzomib and venetoclax – avoid regimens with these agents or use them with other agents the patient has not previously seen (e.g., Pomalyst with cyclophosphamide or elotuzumab and dex).

PI/IMID/CD38 MAB (TRIPLE-REFRACTORY) DISEASE 1.0 Median OS: 8.6 months (95%, CI 7.2–9.9)

0.8

0.6 OS

The MAMMOTH Trial • Retrospective study of 275 patients with MM refractory to CD38 mAb therapy from 14 academic institutions • Triple-refractory: CD38 mAb + 1 PI + 1 IMiD • Quad-refractory: CD38 mAb + 1 PI + 2 IMiDs OR 2 PIs and 1 IMiD • Penta-refractory: CD38 mAb + 2 PIs + 2 IMiDs • 54% triple- / quad-refractory, 25% penta-refractory • Median 4 prior lines of therapy (range 1–16)

11.2 months

0.4

Not triple-refractory (N=57)

Refractory (%) Bortezomib

68.4%

Carfilzomib

47.3%

Lenalidomide

76.7%

Pomalidomide

65.1%

9.2 months

0.2 5.6 months

Triple- and quad-refractory (N=148)

P=0.002

0.0 0

Penta-refractory (N=70)

10

CI, confidence interval; IMiD immunomodulatory drug; mAb, monoclonal antibody; MM, multiple myeloma; OS, overall survival; PI, proteasome inhibitor.

Gandhi UH, et al. Leukemia. 2019;33:2266-75.

20

30 Months

40

50

BCMA IN MULTIPLE MYELOMA

• Expressed on late memory B cells committed to PC differentiation and PCs • BCMA plays a role in survival of long-lived PCs • γ-secretase cleaves BCMA from the cell surface, yielding soluble BCMA

Cho SF et al. Front Immunol 2018;10:1821

TECLISTAMAB: A BCMA-TARGETED BISPECIFIC ANTIBODY 70

62.0% (93/150)

60 50

≥CR: 28.7%

40

21.3%

7.3%

30 20

sCR 29.3%

• • • • •

CR VGPR

10 0

≥VGPR: 58.0%

4.0%

PR

High risk CGs: 25.9% Extramedullary plasmacytomas: 17.0% Median prior lines of therapy: 5 (2 – 14) Triple refractory: 77.6% Refractory to last line of therapy: 89.7%

Moreau, P et al. ASH 2021.

• Median follow-up 7.8 months • 9-Month DoR: 92.5% • 9-Month PFS: 58.5%

MAJESTEC-3 Daratumumab + Teclistamab R A N D O M I Z E

Daratumumab, Bortezomib, and Dexamethasone

Daratumumab, Pomalidomide, and Dexamethasone

1o Endpoint • PFS

CILTACABTAGENE AUTOLEUCEL: A BCMATARGETED CAR T CELL THERAPY ORR: 97.9% (95/97)

•

100%

•

80% Patients, %

CARTITUDE-1

• •

60%

82.5%

40%

≥VGPR: 94.9%

• • •

Phase Ib/II study of the CAR T cell product ciltacabtagene autoleucel for RRMM High risk CGs 23.7% Extramedullary plasmacytomas 13.4% Median prior lines of therapy: 6 (3 – 18) Triple refractory 87.6% Refractory to last line 99%

20% 0%

3.1% Best response =

12.4%

sCR

VGPR

PR

Of the 61 patients evaluable for MRD, 92% were MRD-negative (at 10-5) Martin, T et al. ASH 2021.

CILTACABTAGENE AUTOLEUCEL: PFS AND OS Progression-Free Survival 100

Overall Survival 100

2-year PFS: 100%

2-year OS: 100% 2-year OS: 100%

2-year PFS: 91.0% (95% CI, 67.1–97.8)

80

80

60

Patients (%)

Patients (%)

2-year OS: 74.0% (95% CI, 61.9–82.7) Median OS not reached (95% CI, 27.2 months–NE) 2-year PFS: 60.5% (95% CI, 48.5–70.4) Median PFS not reached (95% CI, 22.8 months–NE)

40

40

20

20

0

60

0 0

Patients at risk All patients 97 MRD negativity ≥6 months 30 MRD negativity ≥12 months 18

3

6

9

12

15

95 30 18

85 30 18

77 30 18

74 30 18

67 29 18

18

Months 63 29 18

All patients

Martin, T et al. ASH 2021.

21 36 17 12

24

27

30

33

36

19 12 10

4 2 1

1 1 1

1 1 1

0 0 0

Patients at risk All patients MRD negativity ≥6 months MRD negativity ≥12 months

MRD negativity sustained ≥6 months

0

3

6

9

12

15

97 30 18

96 30 18

91 30 18

88 30 18

85 30 18

81 30 18

18

21

Months 78 30 18

46 17 12

24

27

30

33

36

23 13 11

8 3 2

2 1 1

1 1 1

0 0 0

MRD negativity sustained ≥12 months

CARTITUDE-6 Induction Six, 28-day Cycles

Consolidation

Maintenance

Ciltacabtagene Autoleucel

Len up to 2 years

D-RVd

R A N D O M I Z E

Dara D1, 8, 15, 22 C1 and C2; D1 and 15 for C3 – C6 V 1.3 mg/m2 IV/SC days 1, 4, 8 and 11 R 25 mg D1 – 14 d 20 mg days 1, 2, 8, 9, 15, 16

Consolidation Two, 28-day Cycles

Induction Four, 28-day Cycles

RVd

Dara D1, 8, 15, 22 C1 and C2; D1 and 15 for C3 – C6 V 1.3 mg/m2 IV/SC days 1, 4, 8 and 11 R 25 mg D1 – 14 d 20 mg days 1, 2, 8, 9, 15, 16

1o Endpoint • PFS • Sustained MRD- CR

A S C T

RVd

V 1.3 mg/m2 IV/SC days 1, 4, 8 and 11 R 25 mg D1 – 14 d 20 mg days 1, 2, 8, 9, 15, 16

Len up to 2 years .

BACK TO OUR PATIENT The patient chooses therapy with idecabtagene vicleucel followed by iberdomide maintenance as part of the KarMMA-7 trial and achieves an MRD negative complete response. Treatment is complicated by moderately severe cytokine release syndrome early on and low-grade neurologic changes, all of which resolves by the 3rd week after treatment.

Two years later, he remains in an MRD negative complete response and is tolerating iberdomide maintenance well.

CONCLUSIONS •

Myeloma relapses, but we have many effective tools!

•

•

Patients are living longer than ever.

Precision medicine is emerging in multiple myeloma •

Venetoclax in t(11;14)+ myeloma, BRAF/MEK inhibitors for patients with RAS and BRAF mutations.

•

BCMA-targeted treatment is transforming the treatment of myeloma

•

Clinical trial participation is key to improving the care for ALL patients

•

Going forward •

Improving access to the most effective therapies, bringing the most effective therapies in late relapse to early relapse and newly diagnosed disease, optimal treatment beyond BCMA-targeted therapy, focus on high-risk patients (frail patients and those with high-risk disease biology).

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

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.

M-Power = Myeloma Power We want to empower patients and communities to CHANGE the current course of myeloma: Increase awareness and reduce stigma Provide quality education through deep community engagement Shorten the time to diagnosis through self advocacy and health care education Educate providers about culturally competent care Support the myeloma community 87

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 Announcement & Press Release • 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

91

M-Power Website

92

Education for Primary Care Providers Remember that there is typically a DELAY in diagnosis of myeloma in all patients

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

Best Practices for Nurses The IMF Nurse Leadership Board published a paper on Best Nursing Practices

Current and Upcoming Geographies

M-Power Community Workshops Adjacent, targeted states States under 2023 consideration Patient advocacy panel

Please reach out to us!

Website myeloma.org IMF InfoLine 800 452 CURE (2873)

Website m-power.myeloma.org

We have had over 250,000 hits on the M-Power website!!

Communicating with your Healthcare Team:​ A 2-Way Street​ Amy E. Pierre, RN, MSN, ANP-BC Memorial Sloan Kettering Cancer Center, Flatiron Health & IMF Nurse Leadership Board

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

HOW PATIENTS WITH MYELOMA COMMONLY PRESENT

ROUTINE PHYSICAL • Patient with few/no symptoms • Abnormal blood work

VISIT FOR SPECIFIC COMPLAINT • Persistent symptom or injury • Abnormal test result (eg, x-ray)

NON-EMERGENCY; More time for shared decision-making

EMERGENCY ROOM • Severe pain—often spinal fractures • Kidney failure

MEDICAL EMERGENCY; need immediate treatment!

Brigle K, et al. J Adv Pract Oncol [in press]. Brigle K, et al. Clin J Oncol Nurs. 2017;21(5 suppl):60-76. Faiman B, et al. J Adv Pract Oncol. 2016;2016:7(suppl 1):17-29. Kurtin S, et al. J Adv Pract Oncol. 2016;7(suppl 1):59-70.

102

SHARED DECISION MAKING: TAKE CHARGE OF YOUR CARE 

Keep a contact list of your providers



Understand the different roles



Orchestrate your care



Consult a specialist

Subspecialists General Hem/Onc

Primary Care Provider (PCP)

Be M-Powered You and Your Caregiver(s) ► Ask questions ► Participate in decisions Myeloma Specialist Family/Support Network ► Communicate effectively with your entire team Allied Health Staff 103

WHAT TO COMMUNICATE ► Family History ► Risk factors also include Black race, male, age, obesity

► Symptoms ► Don’t ignore or self-medicate for pain ► Avoid the emergency room

► Side Effects ► Questions About Test Results and Treatments ► YOUR Priorities, Preferences and Goals for Treatment

DISCUSS: SYMPTOMS AND SIDE EFFECTS Myeloma cells in excess can cause symptoms

Treatments for myeloma kill myeloma cells but can cause symptoms

• • • •

• • • •

Calcium elevation Renal dysfunction Anemia Bone pain

• Fatigue • Infection • Other symptoms

Myelosuppression Peripheral neuropathy Diarrhea Fatigue

• Deep vein thrombosis • Infection (eg, shingles) • Other symptoms

Myeloma and Treatments Both Contribute to How You Feel 105

EXAMPLE: STEROID SIDE EFFECTS AND MANAGEMENT Steroid Side Effects • Irritability,

mood swings, depression

• Blurred vision, cataracts • Flushing/sweating

• Difficulty sleeping

• Stomach bloating,

• Increased risk of

• Weight gain, hair

(insomnia), fatigue

infections, heart disease • Muscle weakness, cramping

hiccups, heartburn, ulcers, or gas thinning/loss, skin rashes

• Increase in blood

sugar levels, diabetes

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

Steroids help kill myeloma cells.

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

• Increase in blood pressure,

water retention

King T, Faiman B. CJON. 2017; 21(5)suppl:240-249. Faiman B, et al. CJON. 2008;12(3)suppl:53-63.

106

EXAMPLE: GI SYMPTOM 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

• 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

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

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

10 7

107

EXAMPLE: 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.

Noonan K, et al. CJON. 2017;21(5)suppl:37-46. Rome S, et al. CJON. 2008;12(3)suppl:21-8.

108

EXAMPLE: 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

Faiman B, et al. CJON. 2017;21(5)suppl:19-36. Tariman, 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 10

109

DISCUSS: FATIGUE, ANXIETY & DEPRESSION All can affect quality of life and relationships • Physical sources include anemia, pain, reduced activity, insomnia, treatment toxicity, bone marrow suppression • Additional sources include financial concerns, end-of-life concerns, and changes in social and sexual function

Management

• Exercise (walking, yoga, etc) • Proper rest • Support (social network, support group, professional counseling, etc) • Prayer, meditation, spiritual support • Mindfulness-based stress reduction

• • • • •

Medications Massage, aroma therapy Supplements: ginseng Transfusion, if indicated Effective management of other symptoms

At least 70% of patients experience fatigue, but only 20% tell their Often, people do not share these symptoms with their provider. provider. Let your provider know about symptoms arewell not controlled well Talk to your provider about symptoms thatthat are not or controlled thoughts or thoughts of self harm. of self harm.

Help is available.

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

DISCUSS: INFECTION PREVENTION & TREATMENT Compromised immune function comes from both multiple myeloma and from treatment • Personal hygiene (skin, oral) • Environmental (wash hands, avoid crowds and sick people, etc) • Growth factor (Neupogen [filgrastim]) • Immunizations (NO live vaccines) • Medications (antibacterial, antiviral) Report fever of more than 100.4°F, shaking chills even without fever, dizziness, shortness of breath, low blood pressure to HCP as directed.

Infection is serious for myeloma patients!

111

ASH 2017 Abstract #903

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

DISCUSS: FINANCIAL BURDEN Financial burden comes from: •

•

Medical costs o Premiums o Co-payments o Travel expenses o Medical supplies

See M-PowerCharlotte.myeloma.org

Prescription costs

Loss of income o Time off work or loss of employment o Caregiver time off work • Ask about a social worker, financial or nurse navigators at your hospital or clinic for assistance

•

112

HOW AND WHEN TO DISCUSS PRIORITIES 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

TIPS FOR COMMUNICATING WITH YOUR TEAM • Reflect on what’s important to you before each visit How well will treatment work? Quality of life? Risks and side effects?

• Ask questions • Take notes • Bring along a listener • Ask for time to consider your options • Continue to learn about Myeloma so you are more comfortable with the conversation

IMF HAS MANY FREE RESOURCES TO HELP YOU

www.m-powercharlotte.myeloma.org/

www.myeloma.org

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

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