ONS 2022

New Drugs, Regimens, and Strategies for Multiple Myeloma: Case Studies for Nurses Slides available for download at:

https://www.imf-ons.myeloma.org/ONS_2022.pdf Please help us have an on-time start.

Please do not save seats. Please silence cell phones. .

Thank you for coming!

1.5 CNE credits are jointly provided by the Annenberg Center for Health Sciences and the International Myeloma Foundation. Educational grants provided by AbbVie, Inc.; Amgen; Bristol Myers Squibb Company; GlaxoSmithKline; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Karyopharm Therapeutics; and Takeda Pharmaceuticals U.S.A., Inc.

ONS Disclaimer Meeting space has been assigned to provide a Symposium supported by the International Myeloma Foundation (IMF) during the Oncology Nursing Society’s (ONS) 47th Annual Congress, April 27-May 1, 2022, in Anaheim, CA. The Oncology Nursing Society’s assignment of meeting space does not imply product endorsement.

Accreditation/Certification Annenberg Center for Health Sciences at Eisenhower is accredited as a provider of nursing continuing professional development education by the American Nurses Credentialing Center’s Commission on Accreditation.

A maximum of 1.5 contact hours may be earned for successful completion of this activity.

Disclosure of Conflicts of Interest It is the policy of the Annenberg Center for Health Sciences at Eisenhower to ensure fair balance, independence, objectivity, and scientific rigor in all programming. All individuals with the potential to impact the content of an accredited education activity are expected to identify and reference off-label product use and disclose relevant financial relationships with ACCME-defined ineligible companies.

The Annenberg Center for Health Sciences assesses relevant financial relationships with its instructors, planners, managers, and other individuals who are in a position to control the content of CE/CME activities. All relevant financial relationships that are identified are thoroughly vetted by the Annenberg Center for fair balance, scientific objectivity of studies utilized in this activity, and patient care recommendations. The Annenberg Center is committed to providing its learners with high-quality CE/CME activities and related materials that promote improvements or quality in healthcare and not a specific proprietary business interest of an ineligible company.

Patient names, demographics, and identifying characteristics have been masked to be HIPAA compliant.

Off-label use of drugs may be discussed.

Slides available for download at:

https://www.imf-ons.myeloma.org/ONS_2022.pdf Presenters’ disclosures are in the Guidebook.

HIPAA = Health Insurance Portability and Accountability Act.

New Drugs, Regimens, and Strategies for Multiple Myeloma: Case Studies for Nurses

Faculty Introductions Chair Beth Faiman, PhD, RN, MSN, APRN-BC, AOCN, BMTCN, FAAN Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH Faculty Kim Noonan, DNP, RN, ANP-BC, AOCN Dana-Farber Cancer Institute, Boston, MA Donna Catamero, ANP-BC, OCN, CCRC Mount Sinai Health System, New York, NY

7

We Hope You Have an Enjoyable and Educational Time: Learning Objectives As a result of this program, you will be able to:

Discuss treatment regimens for patients with newly diagnosed or relapsed multiple myeloma (MM), including appropriate symptom management and patient education

Identify health care disparities faced by patients with MM who are members of minority groups and strategies to overcome these disparities

Describe strategies to support the patient’s input in therapeutic decisions

8

In Your Handout: Resources to Enhance Your Ability to Care for Your Patients With Multiple Myeloma

RESOURCES ALSO AVIALBLE ON LINE http://imf-ons.myeloma.org/resources password: ons2022 9

Agenda TIME

TOPIC

FACULTY

12:15 PM – 12:20 PM

Overview

Beth Faiman

12:20 PM – 12:25 PM

Knowledge Pre-Test

Beth Faiman

12:25 PM – 12:40 PM

Newly Diagnosed Multiple Myeloma, Including Treatment Disparities

Kim Noonan Beth Faiman

Smoldering Multiple Myeloma, Case Study 1: Newly Diagnosed Multiple Myeloma, Disparities, Patient Education, Response, Minimal Residual Disease, Survivorship Care, Myeloma Research Update

12:40 PM – 1:10 PM

Relapsed Multiple Myeloma Case Studies 2 and 3: Relapsed Multiple Myeloma, Treatment for Relapsed Myeloma, Patient Management, Myeloma Research Update

1:10 PM – 1:40 PM

Emerging Therapies in MM, Including CAR T-Cell Therapies and Bispecific Antibodies Case Studies 4 and 5: Relapsed Myeloma, Drugs in Development, Clinical Trials, Myeloma Research Update

1:40 PM – 1:45 PM

CAR = chimeric antigen receptor.

Knowledge Post-Test, Closing Remarks

Donna Catamero Beth Faiman

Donna Catamero Beth Faiman All

10

International Myeloma Foundation 800-452-CURE (2873) http://myeloma.org

Newly Diagnosed Multiple Myeloma, Including Treatment Disparities CASE 1: Anthony* *HIPAA-compliant; not actual patient name.

Kim Noonan, DNP, RN, ANP-BC, AOCN Beth Faiman, PhD, RN, MSN, APRN-BC, AOCN, BMTCN, FAAN

HIPAA = Health Insurance Portability and Accountability Act.

Myeloma Is a Cancer of Plasma Cells Bone Marrow of Patient With MM

Image: American Society of Hematology MM = multiple myeloma.

Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33.

12

Plasma Cells Are Differentiated B Cells That Produce Antibodies B-cell malignancies have characteristics similar to the stages of B-cell development.1,2 Lymph node Transitional B cell

Hematopoietic stem cell (in bone marrow)

Immature B cell (in bone marrow)

B-cell Malignancies 1 Pre-B acute lymphoblastic leukemia (ALL)

1

2 Chronic lymphocytic leukemia (CLL) with unmutated IGHV 2 Mature B cell

3 Burkitt lymphoma (BL)

3

5

4 Follicular lymphoma (FL)

8 4

5 Diffuse large B-cell lymphoma (DLBCL)

FDC

Bone

6

9 Memory B cell

6 Activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) 7 Mantle cell lymphoma (MCL) 8 Marginal zone lymphoma (MZL)

T cell Plasmablast

7

10 11

9 Chronic lymphocytic leukemia (CLL with mutated IGHV) 10 Multiple myeloma (MM)

Plasma cell

FDC = follicular dendritic cell; GC = germinal center; IGHV = immunoglobulin heavy chain variable.

Pal Singh S, et al. Mol Cancer. 2018;17(1):57. Pasqualucci L. Immunol Rev. 2019;288(1):240-261.

11 Waldenström macroglobulinemia (WM)

13

Myeloma Cells Can Produce Myeloma Protein Continually: Detectable in Plasma and Urine Myeloma Normal Myeloma Albumin Albumin

beta

Bone

alpha-1 alpha-1 alpha-2 alpha-2

beta beta

gamma

gamma

Note: Some patients have nonsecretory disease that does not produce detectable myeloma protein.

Understanding Your Test Results, International Myeloma Foundation 2018.

14

Multiple Myeloma Continuum ACTIVE MM

SMM Low Risk Risk of Progression: ≈ 1% per year

MGUS Spike on SPEP/UPEP Abnormal Freelite Test Bone Marrow < 10% PCs

MGRS* PREMALIGNANT CONDITIONS

MONITOR

High Risk: Likely to Progress to Active MM Within 2 Years M-spike ≥ 2 g/dL Freelite Ratio ≥ 20% Bone Marrow ≥ 20% PCs

CLINICAL TRIAL

CRAB Criteria Calcium Elevation Renal Dysfunction Anemia Bone Lesions MDEs Bone Marrow ≥ 60% PC Freelite Ratio ≥ 100 CCR < 40 mL/min MRI  1 focal lesion ≥5mm

TREAT

CCR = creatinine clearance rate; MDE = myeloma-defining event; MGUS = monoclonal gammopathy of undetermined significance; MM = multiple myeloma; MRI = magnetic resonance imaging; PC = plasma clone; SMM = smoldering multiple myeloma; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis. aMonoclonal

gammopathy of renal significance (MGRS) does not meet criteria for myeloma but has kidney manifestation; kidney biopsy is the gold standard for diagnosis.

Rajkumar SV, et al. Lancet Oncol. 2014;15(12):e538-48. Bridoux F, et al. Kidney Int. 2015;87(4):698-711. Terpos E, et al. Lancet Oncol. 2021;22(3):e119-e130. Hillengass J, et al. Lancet Oncol. 2019;20(6):e302-e312.

15

iStopMM Clinical Study: New Insights About MGUS and SMM • MGUS was not associated with SARS-CoV-2 susceptibility or COVID-19 severity • 80,759 individuals

screened in Iceland • 75,422 provided serum sample

for screening→MGUS, SMM, and MM identified • deCODE genetics available

for all participants • Analysis of study data has

provided new insights

• MGUS and SMM occurred at higher rates than expected – 4.9% had MGUS – 0.5% of people ≥40 years had SMM, with one-third at intermediate or high risk of progression • New reference intervals for serum FLC and FLC ratio for use in patients with decreased kidney function WATCH FOR New iStopMM results as analyses continue

COVID-19 = coronavirus disease 2019; FLC = free light chain; iStopMM = Iceland Screens Treats or Prevents Multiple Myeloma; MGUS = monoclonal gammopathy of undetermined significance; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SMM = smoldering multiple myeloma.

Kristinsson SY, et al. ASH 2021. Abstr #156. Rögnvaldsson S, et al. ASH 2021. Abstr #154. Thorsteinsdottir S, et al. ASH 2021. Abstr #151. Long TE, et al. ASH 2021. Abstr #541.

16

Characteristics Put Some at Higher Risk for Multiple Myeloma Family History of MM

Black Race

Obesity

RISK FACTORS

Age

Environmental or Occupational Exposures

Male Sex

MGUS or Other Plasma Disorder

MM = multiple myeloma; MGUS = monoclonal gammopathy of undetermined significance.

National Cancer Institute. Plasma cell neoplasms (including multiple myeloma) treatment (PDQ®) – Patient Version. Accessed February 22, 2021. http://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq?redirect=true#keypoint8. Tariman JD. Multiple myeloma. In: Yarbro CH, et al, eds. Cancer Nursing: Principles and Practice.

Jones and Bartlett Publishers; 2005:1460-1489. Sergentanis TN, et al. Clin Lymphoma Myeloma Leuk. 2015;15(10):563-577.

17

Median Age at Diagnosis Varies by Ethnicity

62

63

64

65

66

Hispanic Patients

Black Patients

65

66

YEARS

YEARS

67

68

69

70

Asian Patients

69

YEARS

71

72

White Patients

71

YEARS

The median age at diagnosis for all patients is

69 years MM = multiple myeloma.

These images are from http://www.shutterstock.com: 129923210, 80373427, 525699067, 603640064.

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

18

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 • Renal 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.

19

CASE 1 Anthony*

Anthony* PATIENT NOTES: • • • •

62-year-old man with back pain Went to chiropractor Pain persisted; went to PCP → NSAIDs 3 days later, new symptoms: shortness of breath, swelling, lethargy, confusion • Wife took him to the ER BLOOD WORK:

Serum creatinine 2.6 g/dL (ULN: 1.3 g/dL) Elevated calcium

NEPHROLOGY WORKUP:

Monoclonal proteinuria, M spike (M-protein) detected

IMAGING:

X-ray → MRI

ER = emergency room; HIPAA = Health Insurance Portability and Accountability Act; M-protein = monoclonal protein; M spike = monoclonal spike; MRI, magnetic resonance imaging; NSAID = nonsteroidal anti-inflammatory drug; ULN = upper limit of normal.

*HIPAA-compliant, not actual patient name, stock photo.

20

CASE 1 Anthony*

Anthony*

MYELOMA WORKUP PERIPHERAL BLOOD:

Calcium:

11.4 mg/dL (ULN: 10.6 mg/dL)

Albumin:

3.3 mMol/L (LLN: 3.5 mMol/L)

B2M:

5.3 mg/dL (ULN: 2.64 mg/dL)

LDH:

150 U/mL (ULN: 250 U/mL)

Creatinine:

2.6 mg/dL (ULN: 1.3 mg/dL) GFR (calculated): 27 mL/min/1.73 m2

Hgb:

10.8 g/dL

κFs:

1832.0 g/dL (normal range: 3.3-19.4 g/dL)

κ/λ-light-chain ratio:

122 (ULN: 1.65)

Urine M spike:

2.72 g/24 h *HIPAA-compliant, not actual patient name, stock photo.

B2M = beta-2 microglobulin; GFR = glomerular filtration rate; Hgb = hemoglobin; HIPAA = Health Insurance Portability and Accountability Act; κ/λ = kappa to lambda; κFs = kappa free serum; LDH = lactate dehydrogenase; LLN = lower limit of normal; M spike = monoclonal spike; ULN = upper limit of normal.

21

CASE 1 Anthony* • • • •

Admitted to hospital Diagnosis: Active multiple myeloma Diagnosis: Renal insufficiency Treatment goals: stabilize; address renal insufficiency

TREATMENT:

VCd initiated in hospital

REFERRAL:

Oncology for ongoing care (outpatient) *HIPAA-compliant, not actual patient name, stock photo.

HIPAA = Health Insurance Portability and Accountability Act; M-protein = monoclonal protein; M spike = monoclonal spike; NSAID = nonsteroidal anti-inflammatory drug; ULN = upper limit of normal; VCd = bortezomib cyclophosphamide dexamethasone.

27 22

Diagnostic Workup for Multiple Myeloma LAB TESTS

• • • • •

gain(1q)

Serum protein electrophoresis (SPEP) Urine protein electrophoresis (UPEP) CBC + differential + chemistry, including albumin and B2M, + LDH FLC levels and ratio (plasma) Monoclonal protein analysis (MPA)

t(4;14)

BONE MARROW BIOPSY

• • •

FISH Cytogenetics Clonal plasma cell percentage

del(17)p

FISH detects abnormalities in MM cells by using fluorescent probes

B2M = beta-2 microglobulin; CBC = complete blood count; FISH = fluorescence in situ hybridization; FLC = free light chain; LDH = lactate dehydrogenase; MM = multiple myeloma.

Ghobrial IM, et al. Blood. 2014;124:3380-3388. Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-3548. Faiman B. Clin Lymphoma Myeloma Leuk. 2014;14:436-440.

23

Recommended Imaging for Multiple Myeloma OLD

NEW WBLDCT Best for early screening for bone disease

PET/CT Response assessment: active residual disease

MRI

Traditional skeletal survey with x-rays

WB or spine + pelvis

Gold standard to assess bone marrow involvement

NOTE: Bone scan (DEXA) for bone density, not for MM

CT = computed tomography; DEXA = dual-energy x-ray absorptiometry; MM = multiple myeloma; MRI = magnetic resonance imaging; PET = positron emission tomography; WB = whole body; WBLDCT = whole-body low-dose computed tomography.

Hillengass J, et al. Lancet Oncol. 2019;20(6):e302-e312. Rome SI, et al. Clin J Oncol Nurs. 2017;21(5 suppl):47-59. Faiman B. Clin Lymphoma Myeloma Leuk. 2014;14:436-440. Dimopoulous M, et al.

Leukemia. 2009;23(9):1545-1556.

24

Health Disparities in Multiple Myeloma Among Black Patients MM is one of the malignancies with the greatest disparity in incidence and prevalence between Black and White Americansa

Minority patients have experienced more cancer care disruptions during the COVID-19 pandemic

What Can Nurses Do to Combat Disparities in MM Care?

• •

~10% of Black patients have MGUS; MM is the most common blood cancer in Black patients

Black patients are less likely to receive life-extending therapies such as ASCT, IMiDs, PIs

Black patients tend to have lower-risk disease due to biologic differences in MM

Black patients achieve better outcomes when they receive equal therapy

•

• •

Be aware of higher rates and earlier age of onset of MGUS and MM in Black patients Strive to become aware of potential conscious or unconscious biases Ensure equal access to centers of excellence and treatments (eg, ASCT, IMiDs, PIs, clinical trials), and supportive care Engage in culturally competent care Encourage Black patients with MM to connect, eg, https://mpower.myeloma.org/

ASCT = autologous stem cell transplant; COVID-19 = coronavirus disease 2019; IMiD = immunomodulatory imide drug; MM = multiple myeloma; PI = protease inhibitor. aData derived

by calculating the ratio of the average age-adjusted incidence rates for Black and White patients from 2000 to 2013 for the 8 most common malignancies in Black patients, plus all cancer sites and MM. Incidence rates were obtained from National Cancer Institute. Fast stats. Surveillance, Epidemiology, and End Results Program website. Accessed March 3, 2022. https://seer.cancer.gov/.

Dong J, et al. Blood Cancer J. 2022;12(2):34. El-Khoury H, et al. ASH 2021. Abstr #152. Pierre A, Williams TH. Clin J Oncol Nurs. 2020;24(4):439-443. Greenberg AJ, et al. Blood Cancer J. 2015;4:e2713. Baker A, et al.

Blood. 2013;12(16):3147-3152. Waxman AJ, et al. Blood. 2010;116(25):5501-5506. Hari PN, et al. Biol Blood Marrow Transplant. 2010;16:395-402. Saraf SL, et al. Bone Marrow Transplant. 2013;48:319-320. Rhotagi N, et al. Am J Clin Oncol. 2007;30(5):540-548. Ailawadhi S, et al. Br J Haematol. 2012;158:91-98. Doroshow D, et al. Ann Oncol. 2020;31:S1204. Hultcrantz M, et al. Blood Cancer Discov. 2020;1:234-243. International Myeloma Foundation website. Accessed March 4, 2022. http://www.myeloma.org.

25

Nurse’s Role Is Crucial to Patients With Multiple Myeloma

INFORM PATIENTS • Build trust; “read the room” • Educate patients and caregivers on disease, what to watch for, protecting health; may need follow-up conversations • Provide information about treatment options, managing AEs

EMPOWER PATIENTS • Encourage questions from patients and caregivers • Encourage communication with medical team • Coach patient on how to participate in decision-making

ADVOCATE FOR PATIENTS • Identify services (eg, financial counseling, financial programs, support groups) • Speak up on behalf of the patient • Ensure medical team is aware of patient concerns/priorities

REDUCE DISPARITIES: Use cultural competency strategies as you inform, empower, and advocate.

AE = adverse event; MM = multiple myeloma.

Gerber L. Nursing. 2018;48(4):55-58. Pierre A, Williams TH. Clin J Oncol Nurs. 2020;24(4):439-443.

26

Recommended Cultural Competency Strategies • • • • • •

Show respect for cultural diversity Display a willingness to learn from patients Have an ethnically diverse health care team Appreciate/respect the role of the family in decision-making Invest in and gain family trust Acknowledge/respect the role religion plays in decision-making; participation in health activities can be influenced by church/religious leaders and can also be a foundation for information • Avoid stereotyping and generalizations • Build rapport and trust • Address according to cultural preference

Steinbeck M, Coleson K. J Adv Pract Oncol [in press]. Pierre A, Williams TH. Clin J Oncol Nurs. 2020;24(4):439-443.

27

Knowledge Is Power: Steep Learning Curve for Patients Newly Diagnosed With Multiple Myeloma • Patient education is crucial but can be overwhelming • Shock of diagnosis makes understanding and retaining information difficult – Tell patients, but also give written or electronic information they can refer to – Refer patients to reliable sources of information – Engage caregivers or extended family IMF Website http://myeloma.org

IMF TV Teleconferences

https://www.cancer.org

Leukemia & Lymphoma Society https://www.lls.org https://www.cancer.gov Free Download or Order From myeloma.org IMF = International Myeloma Foundation.

Multiple Languages

28

Important Education for Newly Diagnosed Patients INFECTION PREVENTION • • • • •

KIDNEY HEALTH

Avoid crowds Ensure handwashing, hygiene Growth factor (eg, filgrastim) IVIG for hypogammaglobulinemia Immunizations (NO live vaccines)

Risks

– COVID-19 vaccination + booster(s) – Pneumococcal 20-valent conjugate vaccine – Seasonal inactivated influenza vaccine (×2 or high-dose) – Shingles vaccine: zoster vaccine recombinant, adjuvanted

• Avoid certain medications (contrast dyes, NSAIDS)

• COVID-19 prevention – Antibody levels – Tixagevimab co-packaged with cilgavimab

• Active MM (M-protein, casts) • High calcium Prevention

• Hydration Treatment • Address underlying myeloma causing renal disfunction

BONE HEALTH • Hypercalcemia from bone destruction can affect kidneys • ≈ 85% of patients with MM develop bone disease Monitor • Report new or worsening bone pain, Medical Testing or Intervention • Monitor serum calcium levels • Imaging may be needed depending on type and location of pain (eg, MRI, PET-CT) • Bone-modifying agents

• Dose adjustments may be needed for reduced kidney function

COVID-19 = coronavirus disease 2019; IVIG = intravenous immunoglobulin; M-protein = monoclonal protein; MM = multiple myeloma; NSAID = nonsteroidal anti-inflammatory drug.

Hillengass J, et al. Lancet Oncol. 2019;20(6):e302-e312. Faiman B, et al. Clin J Oncol Nurs. 2017;21(5 suppl):19-36. Faiman B, et al. Clin J Oncol Nurs. 2011;15(suppl):66-76. Miceli TS, et al. Clin J Oncol Nurs.

2011;15(4):9-23. Rome SI, et al. Clin J Oncol Nurs. 2017;21(5 suppl):47-59. Miceli TS, et al. Clin J Oncol Nurs. 2011;15(4)suppl:9-23. Dimopoulous M, et al. Leukemia. 2009;23(9):1545-1556. Brigle K, et al.

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

29

CASE 1 Anthony* Referred to oncology for ongoing care • Diagnosis: active multiple myeloma • FISH: t(11;14) • R-ISS: 2

*HIPAA-compliant, not actual patient name, stock photo.

FISH = fluorescence in situ hybridization; HIPAA = Health Insurance Portability and Accountability Act; M-protein = monoclonal protein; M spike = monoclonal spike; NSAID = nonsteroidal anti-inflammatory drug; R-ISS = Revised International Staging System; ULN = upper limit of normal.

30

Identified by FISH • t(4;14)a • del(17/17p) • t(14;16) • gain(1q)a • t(14;20)

No abnormalities detected OR

Abnormalities that are not defined as high risk

Identified by karyotyping • Nonhyperdiploid karyotype • del(13)

Genetic analysis • Double hit (biallelic TP53 inactivation or amplification of CKS1B [1q21])

HIGH RISK

STANDARD RISK

Risk With Multiple Myeloma

Other disease characteristics • Extramedullary disease • Plasma cell leukemia

CKS1B = cyclin-dependent kinases regulatory subunit 1 gene; FISH = fluorescence in situ hybridization; TP53 = tumor protein 53. aIntermediate

risk according to Rajkumar SV, high risk according to Sonneveld P, et al.

Sonneveld P, et al. Blood. 2016;127:2955-2962. Rajkumar SV. Am J Hematol. 2018;93:1091-1110. Walker BA, et al. Leukemia. 2019;33(1):159-170.

31

R-ISS Staging System for Multiple Myeloma 5-YEAR OS 5-YEAR PFS

I

• ISS stage I (serum B2M level < 3.5 mg/L and serum albumin ≥ 3.5 g/dL) • No high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)] • Serum LDH < ULN (varied by institution)

82%

55%

II

• Not R-ISS stage I or III

62%

36%

III

• ISS stage III (serum B2M level > 5.5 mg/L) • High-risk CA [del(17p) and/or t(14;4) and/or t(14;16)] or high serum LDH

40%

24%

B2M = beta-2 microglobulin; CA = chromosomal abnormality; ISS = International Staging System; LDH = lactate dehydrogenase; MM = multiple myeloma; OS = overall survival; PFS = progression-free survival; R-ISS = Revised-ISS; ULN = upper limit of normal.

Palumbo A, et al. J Clin Oncol. 2015;33:2863-2869.

BETTER

SURVIVAL

STAGE R-ISS

WORSE 32

Expanding Treatment Options for Multiple Myeloma Alkylator

Antibody drug conjugate

Steroid

Monoclonal antibody (mAb)

Anthracycline

Nuclear export inhibitor

2015 Daratumumab

Proteasome inhibitor (PI)

CAR T-cell therapy

2015 Ixazomib

Immunomodulatory imide drug (IMiD)

1960

1970

1980

2015 Elotuzumab

1990

2000

2010

2020

2003 Bortezomib 1958 Melphalan 1962 Prednisone

1983 Autologous Stem Cell Transplantation

1986 High-Dose Dexamethasone CAR = chimeric antigen receptor; HDAC = histone deacetylase; SC = subcutaneous.

Tariman J. Nurs Clin North Am. 2017;52(1):65-81. DRUGS@FDA.gov.

2013 Pomalidomide

2006 Lenalidomide

2006 Thalidomide

2012 Carfilzomib 2007 Doxorubicin

2019 Selinexor

2018 Denosumab

2021

2020 Daratumumab SC

2022 Ciltacabtagene Autoleucel

2020 Isatuximab

2020 Belantamab Mafodotin

2021 Idecabtagene Vicleucel 33

Myeloma Primary Treatment: 2 Drugs + Steroid Recommended NEWLY DIAGNOSED MM

PRIMARY TREATMENTa

Common Regimens for Non-Transplant Candidate

• • • • •

• Dara-VRd: daratumumab bortezomib lenalidomide dex

• • •

MAINTENANCE a

Common Regimens for Transplant Candidate

• • • •

• • • •

RVdb: lenalidomide bortezomib dex KRd: carfilzomib lenalidomide dex Dara-RVd: daratumumab lenalidomide bortezomib dex IRd: ixazomib lenalidomide dex VCd: bortezomib cyclophosphamide dex (preferred for patients with renal insufficiency)

Lenalidomideb Ixazomib Bortezomib Lenalidomide + bortezomib (for high risk)

• • • • • •

RVdb: lenalidomide bortezomib dex Dara-Rdb: daratumumab lenalidomide dex KRd: carfilzomib lenalidomide dex IRd: ixazomib lenalidomide dex Dara-VMPb: daratumumab bortezomib melphalan prednisone VCd: bortezomib cyclophosphamide dex (preferred for patients with renal insufficiency)

RCd: lenalidomide cyclophosphamide dex Rd: lenalidomide low-dose dex RVd lite: lower-dose lenalidomide bortezomib dex (for frail)

Lenalidomideb Ixazomib Bortezomib Lenalidomide + bortezomib (for high risk)

dex = dexamethasone; MM = multiple myeloma; NCCN = National Comprehensive Cancer Network. aClinical

trial participation is recommended. bNCCN Category 1.

Faiman B, Gleason C. Equipping Nurses to Guide Patients Through the New Therapeutic Landscape of Multiple Myeloma. Accessed February 20, 2021. https://www.clinicaloptions.com/oncology/programs/nursingguiding-mm-patients. Rajkumar SV. How I treat. Accessed May 1, 2020. https://twitter.com/vincentrk/status/1203058085776035840. NCCN Guidelines®. Multiple Myeloma. V5.2022. Accessed March 15, 2022.

34

How Well Treatment Is Working: IMWG Myeloma Response and Relapse Criteria Assessment

CR

VGPR

CR: myeloma protein undetectable in serum or urine (negative immunofixation); no more than 5% plasma cells in BM; no new lytic lesions; plasmacytomas resolved 90% reduction in myeloma protein

Further categorization of CR: sCR, MRD negative

For Nurses:

✓ Order labs regularly ✓ Encourage patients to know who is monitoring

PR MR SD PD

At least 50% reduction in myeloma protein

✓ Monitor for relapse – CRAB symptoms OR increase of 25% in M-protein from lowest point

BM = bone marrow; CR = complete response; CRAB = calcium elevation, renal dysfunction, anemia, bone lesions; IMWG = International Myeloma Working Group; M-protein = monoclonal protein; MR = minimal response (only in relapsed); MRD = minimal residual disease; PD = progressive disease; PR = partial response; sCR= stringent complete response; SD = stable disease; VGPR = very good partial response. aIMWG

minimal residual disease consensus criteria published August 2016.

Palumbo A, et al; International Myeloma Working Group. J Clin Oncol. 2014;32:587-600. Durie BM, et al; International Myeloma Working Group. Leukemia. 2006;20(9):14671473. Kumar S, et al. Lancet Oncol.

2016;17(8):e328-e346.

35

MRD-Negative Correlates With Better Patient Outcomes ClonoSEQ MRD Results

Role of the Nurse in MRD Testing: The Why, When, How, and What

1

WHY?

Total clonal cells/total nucleated cells

10-1

• Predict outcomes • Support treatment decisions • VGPR or better?

10-2

10-3

WHEN?

10-4

• 9 to 12 months into treatment or longer • Retest annually

10-5 HOW?

10-6 Dec 2018

June 2019

Dec 2019 Collection date

June 2020

Dec 2020

• ClonoSEQ—FDA cleared for diagnostic use • Within a clinical trial protocol

WHAT DO THE TESTS MEAN FOR PATIENTS?

• Nice to know vs need to know information

ASCT = autologous stem cell transplant; CR = complete response; FDA = US Food and Drug Administration; MRD = minimal residual disease; VGPR = very good partial response.

Munshi N, et al. Blood Adv. 2020;4(23):5988-5999. ClonoSEQ website. Accessed March 15, 20222. https://www.clonoseq.com/. ClonoSEQ® [technical summary]. Seattle, WA. Adaptive Biotechnologies; 2020. Accessed April 4, 2022. https://www.clonoseq.com/technical-summary/.

36

Daratumumab: Anti-CD38 Monoclonal Antibody • Monoclonal antibody targeting CD38

SC injection

– Original IV dosing and SC formulation

• Multiple indications for MM

– See prescribing information for details

• Clinical pearls

– SC dose form for SC only; IV for IV only – Antibody interference—type and cross BEFORE starting – Premeds: corticosteroids, antipyretics, antihistamine, – – – – – –

and montelukast IRR with IV: ≈ 50% (mostly grade 1 and 2, in first or second infusion) IRR with SC: ≈ 9%; systemic reactions 10% Post-med: oral corticosteroid for 2 days Herpes prophylaxis Remember appropriate prophylaxis for combination partner drugs Educate patients/caregivers about expectations

DRd, VMP + Dara (First-line non-transplant)

Dara -VTd (First-line transplant eligible)

DKd,a DRd, DVd (1 prior therapy)

DPd (2 prior therapies)

Dara monotherapy (3 prior therapies)

Dara = daratumumab; DKd = daratumumab carfilzomib dexamethasone; DPd = daratumumab pomalidomide dexamethasone; DRd = daratumumab lenalidomide dexamethasone; DVd = daratumumab bortezomib dexamethasone; IMiD = immunomodulatory imide drug; IRR = infusion-related reaction; IV = intravenous; MM = multiple myeloma; SC = subcutaneous; VMP = bortezomib melphalan prednisone; VTd = bortezomib thalidomide dexamethasone. a1

to 3 prior therapies.

DARZALEX® (daratumumab) Prescribing Information. DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) Prescribing Information. Gleason C, et al. J Adv Pract Oncol. 2016;7(suppl 1):53-57.

37

Daratumumab: Anti-CD38 Monoclonal Antibody Cont’d SC Clinical Pearls INJECTION INTO ABDOMEN

IV Clinical Pearls 1 Inject 15 mL into

3"

subcutaneous tissue over 3 to 5 minutes

then

SLOW FIRST INFUSION

≈HOURS 7

ALTERNATIVE: DIVIDED FIRST INFUSION

DAY 1 mg/kg

FASTER

3-4

HOURS

after 1st/2nd dose

2 3" from navel on right or left side

SC or IV: SCHEDULES DEPEND on REGIMEN: CHECK PRESCRIBING INFORMATION

3 Pause or slow if patient experiences pain

8

DAY 2 mg/kg

8

DAY 1 and 2 of CYCLE 1: 8 mg/kg

Example: 4-week cycle with Rd WEEKS 1-8

WEEKS 9-24

WEEK 25

WEEKLY

EVERY 2 WEEKS

EVERY 4 WEEKS

(5 doses)

Until progression

(9 doses)

IV = intravenous; SC = subcutaneous.

DARZALEX® (daratumumab) Prescribing Information. DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) Prescribing Information.

• Schedule becomes less frequent • If no injection/infusion reaction after 3 doses, consider discontinuing corticosteroid pre/post medications 38

GRIFFIN: Dara Added to RVd Improves Response Rate and Depth of Response GRIFFIN: phase 3 clinical trial in newly diagnosed transplant-eligible patients with MM • D-RVd (n = 104) vs RVd (n = 103) • Followed by ASCT, consolidation, maintenance for 24 months Conclusions after 24 months of maintenance Dara added to RVd significantly • 99% ORR with D-RVd vs 92% with RVd improved ORR and depth of • Dara doubled percent of MRD-negative patients response, including sCR and – 64.4% MRD negative at 10-5 with D-RVd regimen vs 30.1% RVd (P < 0.0001) MRD negativity sCR Rates with D-RVd and RVd End of Induction

End of ASCT

End of Consolidation

After 1-Year Maintenance

After 2-Year Maintenance

RVd

7%

14%

32%

46%

47%

D-RVd

12%

21%

42%

63%

66%

Continued use of daratumumab with RVd and R maintenance improved depth of response ASCT = autologous stem cell transplant; Dara = daratumumab; D-RVd = daratumumab lenalidomide bortezomib dexamethasone; MRD, minimal residual disease; ORR = objective response rate; RVd = lenalidomide bortezomib dexamethasone; sCR = stringent complete response.

Laubach JP, et al. ASH 2021. Abstr #79.

39

Daratumumab-Based Regimens for Patients With Multiple Myeloma Who Are Transplant Ineligible ALCYONE Phase 3

100

42-Mo PFSa

100

60-month PFS rate 80

Daratumumab monotherapy phase

80 D-Rd: median, NR

60

52.5% Rd: median, 34.4 months

40

20

28.7%

HR, 0.53 (95% CI, 0.43-0.66) P < 0.0001

PFS (%)

Surviving without progression (%)

MAIA Phase 3

60

48% D-VMP: median 36.4 mo

VMP: median 19.3 mo

40

20 HR: 0.42 (95% CI, 0.34-0.51; P < 0.0001)

0

14%

0 0

3

6

9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69

Months

No. at risk Rd 369 333 307 280 255 237 220 205 196 179 172 155 146 133 123 113 105 94 63 36 12 4 2 0

D-Rd 368 347 335 320 309 300 290 276 266 256 246 237 232 222 210 199 195 170 123 87 51 17 5 0

0

At Risk, n

3

6

9

12

15

18

21

24

27

30

33

36

39 42

45

48 51

Months

VMP 356 304 278 263 246 207 171 128 110 93 78 67 51 29 15 7 D-VMP 350 322 312 298 292 265 243 220 207 202 188 173 160 113 63 26

0 9

0 0

D-Rd = daratumumab lenalidomide dexamethasone; D-VMP = daratumumab bortezomib melphalan dexamethasone; HR = hazard ratio; MM = multiple myeloma; PFS = progressionfree survival; Rd = lenalidomide dexamethasone; VMP = bortezomib melphalan dexamethasone. aKaplan-Meier

estimate.

Facon T, et al. EHA 2021. Abstr #LB1901. Mateos MV, et al. ASH 2019. Abstr #859.

40

Bone-Modifying Agents Recommendation: Bone-strengthening agents should be administered for at least 12 months to all patients with newly diagnosed MM with or without bone disease Agent

Notes

Zoledronic acid

• Preferred agent • Also indicated for MM-related hypercalcemia • PFS and OS benefit

Denosumab

• May also be used, particularly in patients with renal impairment • May prolong PFS in patients who are newly diagnosed with MM and are ASCT eligible • Discontinuation is challenging due to rebound effect

Pamidronic acid

• May be used if other agents are not available

ASCT = autologous stem cell transplant; MM = multiple myeloma; OS = overall survival; PFS = progression-free survival.

Terpos E, et al. Lancet Oncol. 2021;22(3):e119-e130.

41

Clinical Pearls for Steroids • Patient education – Steroids kill myeloma cells – Don’t stop or change dose without discussing with provider

• Consistent schedule (AM vs PM) • Take with food • Proactively manage side effects – Glucose – Checklists – Consider dose/timing adjustments with HCP

HCP = health care provider.

King T, Faiman B. Clin J Oncol Nurs. 2107;21(2):240-249. Understanding Dexamethasone and Other Steroids. IMF Brochure.

42

Maintenance Recommended for All Patients After ASCT, Until Progression or Toxicity Lenalidomide Maintenance After Transplant: Meta-Analysis

Ixazomib Maintenance After Transplant: Tourmaline-3 Clinical Trial

Ixazomib

Lenalidomide Placebo Placebo

ASCT, autologous stem cell transplant; HR = hazard ratio; len = lenalidomide; PI = proteasome inhibitor; PFS = progression-free survival.

McCarthy PL, et al. J Clin Oncol. 2017;35(29):3279-3289. Faiman B, et al. J Adv Pract Oncol. 2016:7(suppl 1):17-29. Rajkumar SV. How I treat. Accessed May 1, 2020. https://twitter.com/vincentrk/status/1203058085776035840. Dimopoulous MA, et al. Lancet. 2019;393(10168):253-264. Dimopoulos MA. ASH 2018. Abstr #301.

43

Maintenance Therapy Nursing Implications • Patients on therapy for long time: AE management,

• • • •

adherence, treatment fatigue, no pregnancy with lenalidomide May encounter reimbursement challenges with PI (begin authorization early) Short-term vs long-term effects – Many AEs subside after first few months – Health screening related to long-term use Patients living longer: survivorship care, coordination with PCP, emphasis on healthy behaviors Patient advocacy: understanding patient’s changing needs/desires; advocating with extended health care team

Lenalidomide maintenance 10 or 15 mg days 1-28 of 28-day cycle Ixazomib maintenance 3 or 4 mg days 1, 8, and 15 in 28-day cycle in TOURMALINE-MM3

Bortezomib maintenance 1.3 mg/m2 every 2 weeks Lenalidomide + bortezomib Recommended for high risk

AE = adverse event; ASCT = autologous stem cell transplant; PCP = primary care physician.

Bilotti E, et al. Clin J Oncol Nurs. 2011;15(4 suppl). Kurtin S. In: Tariman JD, et al, eds. Multiple Myeloma: A Textbook for Nurses. 2nd ed. 2015. Dimopoulous MA, et al. Lancet. 2019;393(10168):253-264.

NCCN Guidelines®. Multiple Myeloma. V5.2022. Accessed March 15, 2022. Zhang S, et al. Blood Cancer J. 2020;10:33.

44

Frailty Score Can Predict Survival and Rate of Treatment Discontinuation

Online myeloma frailty score calculator at http:/www.myelomafrailtyscorecalculator.net/ Fit = 0, intermediate = 1, frail = 3

Score

Patients (%)

3-Year Survival (%)

Treatment Discontinuation (%)

0

39

84

17

1

31

76

22

≥2

31

57

25

Calculator takes into account age, comorbidities, and ability to manage daily activities

Palumbo A, et al. Blood. 2015;125(13):2068-2074. International Myeloma Working Group. Myeloma Frailty Score Calculator. Accessed June 30, 2020. http:/www.myelomafrailtyscorecalculator.net/.

45

RVd Lite Regimen: Reduced-Intensity Regimen for Transplant-Ineligible Patients RVd lite Phase 2 Study • Transplant ineligible: N = 53 • Median age: 72 years (range, 65-91) • Grade 3 toxicities: – 34% Hypophosphatemia – 24% Neutropenia – 10% Rash • ORR: 86% • PFS: 41.9 • 5-year OS: 61.3 Conclusions: well-tolerated and highly effective regimen for transplant-ineligible population

Induction (cycles 1-9) Repeat q35 days × 9 cycles Lenalidomide 15 mg PO days 1-21 Bortezomib 1.3 mg/m2 SC days 1, 8, 15, 22 Dexamethasone 20 mg PO days 1, 2, 7, 8, 15, 16, 22, 23 (patients aged ≤ 75 years)

Consolidation (cycles 10-15) Repeat q35 days × 9 cycles Lenalidomide 15 mg PO days 1-21 (or last tolerated dose as of cycle 9) Bortezomib 1.3 mg/m2 SC days 1, 15, 22 (or last tolerated dose as of cycle 9)

ORR = objective response rate; OS = overall survival; PFS = progression-free survival; PO = by mouth; q = every; RVd lite = lower-dose lenalidomide bortezomib dexamethasone; SC = subcutaneous.

O’Donnell EK, et al. Blood. 2019;134(suppl 1):3178. O’Donnell EK, et al. Br J Haematol. 2018;182(2):222-230.

46

CASE 1 Anthony*

TREATMENT:

VCd—in hospital VRd (R dose adjusted for renal impairment; full-dose R after renal function improved) Denosumab

ASCT:

Referral for consult with transplant center

MAINTENANCE:

Planned: R MRD testing

SURVIVORSHIP:

Survivorship care plan

Remember: ✓ Shingles prevention ✓ DVT prophylaxis ✓ Monitor sugars

*HIPAA-compliant, not actual patient name, stock photo.

ASCT = autologous stem cell transplant; DVT = deep vein thrombosis; HIPAA = Health Insurance Portability and Accountability Act; R = lenalidomide; VCd = bortezomib cyclophosphamide dexamethasone; VRd = bortezomib lenalidomide dexamethasone.

47

Survivorship Care Plan: Recommended for Each Survivor and His/Her PCP

Survivorship related image or icons?

Institute of Medicine recommendation: a survivorship care plan for each survivor • Record of care – Diagnosis, including diagnostic tests and results – Treatments received, total dosage, responses, toxicities – Other supportive services (psychosocial, etc) – Contact information for key providers – Point of contact for continuing care

• Follow-up plan – – – – MM = multiple myeloma; PCP = primary care provider.

Ongoing health maintenance therapy/testing Recommended screenings Late/long-term effects of treatments Recommendations/resources for healthy behaviors, support, etc

Institute of Medicine. Cancer Survivorship Care Planning. Fact Sheet Nov 2005. Accessed May 1, 2020. https://apos-society.org/wp-content/uploads/2016/06/factsheetcareplanning.pdf. Salz T, et al.

Cancer. 2014;120(5):722-730. Bilotti E, et al. Clin J Oncol Nurs. 2011;15(4 suppl). Kurtin S. In: Tariman JD, et al, eds. Multiple Myeloma: A Textbook for Nurses. 2nd ed. 2015.

48

Summary MM is a cancer of the plasma cells. Active MM as defined by CRAB criteria and/or myeloma-defining events requires treatment

Disparities exist among minority patients with MM, including disruptions in treatment; nurses can play an important role in reducing disparities

MGUS, MGRS, and/or smoldering MM are premalignant conditions associated with MM

After induction (usually a triplet) ± consolidation (autologous stem cell transplant), maintenance treatment is recommended for all patients with MM

The workup for MM includes laboratory blood work, genetic testing (bone marrow biopsy), and imaging for bone involvement

Nurses play an important role in helping achieve optimal outcomes by informing, empowering, and advocating for patients

CRAB = calcium elevation, renal dysfunction, anemia, bone lesions; MGUS = monoclonal gammopathy of undetermined significance; MGRS = monoclonal gammopathy of renal significance; MM = multiple myeloma.

Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33. Greenberg AJ, et al. Blood Cancer J. 2015;4:e271. Baker A, et al. Blood. 2013;12(16):3147-3152. NCCN Guidelines®. Multiple Myeloma. V3.2021. Accessed February 1, 2021. O’Donnell EK, et al. Blood. 2019;134(suppl 1):3178. O’Donnell EK, et al. Br J Haematol. 2018;182(2):222-230. Gerber L. Nursing. 2018;48(4):55-58.

49

International Myeloma Foundation 800-452-CURE (2873) http://myeloma.org

Relapsed Multiple Myeloma CASE 2: Judy* CASE 3: Melvin* *HIPAA-compliant; not actual patient names.

Donna Catamero, ANP-BC, OCN, CCRC Beth Faiman, PhD, RN, MSN, APRN-BC, AOCN, BMTCN, FAAN

HIPAA = Health Insurance Portability and Accountability Act.

Some Patients With Multiple Myeloma May Be “Functionally Cured”

9% of patients with multiple myeloma were exceptional responders to ASCT with > 8-year progression-free survival in the absence of maintenance therapy

Paquin A, et al. Blood Cancer J. 2020;10(8):87.

51

Relapsing Nature of Multiple Myeloma Clonal Evolution: Dominant Clones Change Over Time First-Line Therapy

M-Protein g/L

10

Second-Line Therapy

≥ Third-Line Therapy

ACTIVE MM ACTIVE MM

5

d

2

MGUS or SMM

ACTIVE MM REMISSION

REMISSION

Time Dominant MM Clones Change over Time

Misc

Clone 1.1

Clone 1.2

Clone 2.1

M-protein = monoclonal protein; MGUS = monoclonal gammopathy of undetermined significance; MM = multiple myeloma; SMM = smoldering multiple myeloma.

Adapted from Durie B. Keats JJ, et al. Blood. 2012;120(5):1067-1076.

Clone 2.2 52

How Patients With Myeloma Relapse Myeloma protein

Asymptomatic Biochemical Relapse • Sequentially rising myeloma protein, free light chain • No other symptoms • Decisions: if, when, how to treat Faiman B, et al. J Adv Pract Oncol. 2016:7(suppl 1):17-29. Kurtin S, et al. J Adv Pract Oncol. 2016;7(suppl 1):59-70.

Symptomatic • New, worsening bone pain • Increasing fatigue, anemia • Next step: relapse workup; many therapy choices 53

Relapse Workup

LAB TESTS

• Serum protein electrophoresis (SPEP) • Urine protein electrophoresis (UPEP) • CBC + differential + chemistry (metabolic panel) • FLC levels and ratio (plasma) • Monoclonal protein analysis (MPA)

CONSIDER BONE MARROW BIOPSY

Cytogenetics and FISH

IMAGING

• • • •

PET/CT Skeletal survey WBLDCT MRI

Albumin

gamma

alpha-2 beta alpha-1

Which imaging depends on individual’s symptoms and available testing options

CBC = complete blood count; CT = computed tomography; FISH = fluorescence in situ hybridization; FLC = free light chain; MRI = magnetic resonance imaging; PET = positron emission tomography; WBLDCT = whole-body low-dose computed tomography.

Rome SI, et al. Clin J Oncol Nurs. 2017;21(5 suppl):47-59. Hillengass J, et. Lancet Oncol. 2019;20(6):e302-e312. Ghobrial IM, et al. Blood. 2014;124:3380-3388. Rajkumar SV, et al. Lancet Oncol.

2014;15:e538-e548. Faiman B. Clin Lymphoma Myeloma Leuk. 2014;14:436-440.

54

Many Treatment Options at Relapse First-Line Therapy FDA-Approved Myeloma Therapies

Second-Line Therapy

≥ Third-Line Therapy

Lines of Therapy

1

2

Bortezomib ✓ ✓ Lenalidomide ✓ ✓ a Carfilzomib ✓ Daratumumab ✓ ✓ a Ixazomib ✓ Elotuzumab ✓ Selinexor ✓ Isatuximab ✓ Pomalidomide Belantamab Mafodotin Idecabtagene Vicleucel Ciltacabtagene Autoleucel Venetoclax (off label) New agents or regimens in clinical trials are always an option

3

✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

≥4

✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓

Common Combinations VRd, Vd VRd, Rd KRd, Kd, DKd, Isa-Kd DRd, DVd, DPd, DVMP, DKd IRd ERd, EPd SVd, Sd Isa-Kd, Isa-Pd Pd, DPd, EPd, PCd, Isa-Pd Bela-d

Vd + ven

ASCT = autologous stem cell transplant; Bela = belantamab; C = cyclophosphamide; D = daratumumab; d = dexamethasone/low-dose dexamethasone; E = elotuzumab; FDA = US Food and Drug Administration; Isa = isatuximab; I = ixazomib; K = carfilzomib; M = melphalan; P = pomalidomide; R = lenalidomide; S = selinexor; V = bortezomib; ven = venetoclax. aIncluded

in National Comprehensive Cancer Network Guidelines® induction therapy.

Prescribing information for each drug listed in the table. NCCN Guidelines®. Multiple Myeloma. V5.2022. Accessed March 15, 2022. Noonan K, et al . J Adv Pract Oncol [in press].

55

IMWG Guideline: First Relapse FIRST RELAPSE

Not refractory to lenalidomide

Refractory to lenalidomide

Alternatives‡: DVd, Kd, DKd, Isa-Kd, IRd, ERd, PVd, or SVd (subject to approval)

Preferred options†: DRd or KRd

If daratumumab, isatuximab, or carfilzomib are not available: Rd, Vd, VTd, VCd, or VMP

Preferred options†: Pom-Vd, D-Kd or Isa-Kd

Alternatives‡: DVd or Kd, Other options§: KPd, DPd, or Ipd If daratumumab, isatuximab, or carfilzomib are not available: VCd, Vd, or VMP

C = cyclophosphamide; D = daratumumab; d = dexamethasone (low dose); E = elotuzumab; FDA = US Food and Drug Administration; IMWG = International Myeloma Working Group; Isa = isatuximab; I = ixazomib; K = carfilzomib; M = melphalan; P = prednisone; PD = progressive disease; Pom = pomalidomide R = lenalidomide; S = selinexor; T = thalidomide; V = bortezomib; ven = venetoclax.

Moreau P, et al. Lancet Oncol. 2021;22(3):e105-e118.

56

Practical Approach to Treatment of Patients With Relapsed Myeloma Disease-related factors • Duration of response to initial therapy • High-risk vs low-risk status • Molecular relapse vs symptomatic relapse • Other comorbid conditions, patient frailty Treatment-related factors • Previous/current therapy exposure and response • • • •

(relapsed vs refractory) Toxicity/tolerability of previous regimen Mode of administration (ie, PO or IV) Cost and convenience (out-of-pocket co-pays for IV vs PO) Patient preference

IV = intravenous; PO = by mouth.

Faiman B, et al. J Adv Pract Oncol. 2016;2016:7(suppl 1):17-29.

57

Carfilzomib: IV Proteasome Inhibitor Kd or DKd ≥ 1 prior linea

• IV proteasome inhibitor, indications: – In combination with dex or len-dex or daratumumab-dex in patients with R/R MM who have received 1 to 3 prior lines of therapy – As a single agent in patients with R/R MM who have received 1 or more lines of therapy

Kd, DKd, K ≥ 1 prior linea

• Clinical pearls – Escalate dose – Dose-dependent 10- or 30-min infusion – Hydration but not overhydration – Premedication (dex) – Aspirin vs full anticoagulation – Monitor blood counts, response – Monitor for infection

20/70 mg/m2 Once weekly 30-min infusion

– Herpesvirus prophylaxis – Know cardiac and pulmonary status and optimize heart failure and blood pressure management – Diuretic (furosemide or torsemide) or inhalers if needed – Avoid dyspnea over the weekend: start new patients’ first dose early in the week

20/56 mg/m2 Twice weekly 30-min infusion

KRd or K ≥ 1 prior linea 20/27 mg/m2 Twice weekly 10-min infusion

d or dex = dexamethasone; DKd = daratumumab carfilzomib dexamethasone; IV = intravenous; K = carfilzomib; Kd = carfilzomib dexamethasone; KRd = carfilzomib lenalidomide dexamethasone; len = lenalidomide; MM = multiple myeloma; R/R = relapsed/refractory. a1

to 3 prior lines of therapy for DKd, KRd, or Kd. Stewart K, et al. N Engl J Med. 2015;372:142-152. KYPROLIS® (carfilzomib) Prescribing Information.

58

IMPEDE VTE Score Can Assess VTE Risk in Patients With Multiple Myeloma Predictor

Acronym

Score

Immunomodulatory Drug

I

4

Body Mass Index ≥ 25 kg/m2

M

1

Pelvic, Hip or Femur Fracture

P

4

Erythropoiesis-stimulating Agent

E

1

Doxorubicin

D

3

Dexamethasone High-Dose Low-Dose

4 2

Ethnicity/Race = Asian/Pacific Islander

E

–3

History of Venus Thromboembolism before MM

V

5

Tunneled Line Central Venous Catheter

T

2

Existing Thromboprophylaxis: Therapeutic LMWH or Warfarin

E

–4

Existing Thromboprophylaxis: Prophylactic LMWH or Aspirin

–3

…the IMPEDE VTE score outperformed the current IMWG guidelines and NCCN Guidelines® and could be considered as the new risk stratification standard for VTE in MM

Cumulative risk of VTE

IMPEDE VTE Score

Days post-treatment

IMWG = International Myeloma Working Group; LWMH = low molecular weight heparin; MM = multiple myeloma; NCCN = National Comprehensive Cancer Network; VTE = venous thromboembolism.

Sanfilippo KM, et al. Am J Hematol. 2019;94(11):1176-1184.

59

Consider Full Anticoagulation for Patients on Carfilzomib Regimens 0%

4%

8%

12%

16%

20%

4.0% RVd + ASA 1.0%

Tip: rivaroxaban co-pay may be covered by LLS grant or other cancer-related assistance IF indicated it is necessary for myeloma treatment

16.5% KRd + ASA 5.2%

KRd + rivaroxaban

2.2%

VTE

2.2%

Bleed

Rivaroxaban may be a more-effective antithrombotic agent for patients on KRd

ASA = aspirin; KRd = carfilzomib lenalidomide dexamethasone; RVd = lenalidomide bortezomib dexamethasone; VTE = venous thromboembolism.

Piedra KM, et al. ASH 2019. Abstr #1835.

60

Ixazomib: Oral Proteasome Inhibitor • Oral proteasome inhibitor – Indication: patients with MM who have received at least 1 prior therapy – In combination with Rd

Ixazomib + Rd (≥ 1 prior therapy)

All-oral regimen

• Administration

•

– Oral capsule 1 × per week; do not crush, chew, or open capsule – Empty stomach: 1 hour before or 2 hours after food Clinical pearls – Adherence, schedule, viral prophylaxis – Rapid response (1.1 months); fast absorption (if vomit, do NOT repeat dose) – Monitor blood counts: cyclic thrombocytopenia – Peripheral neuropathy, peripheral edema – Herpes prophylaxis – In combination with Rd, so DVT prophylaxis

WATCH FOR • New regimens • Clinical trials – IR in SMM – IPd in MM – Others

DVT = deep vein thrombosis; IR = ixazomib lenalidomide; IPd = ixazomib pomalidomide dexamethasone; MM = multiple myeloma; Rd = lenalidomide low-dose dexamethasone; SMM = smoldering MM. NINLARO® (ixazomib) Prescribing Information. Faiman B, et al. J Adv Pract Oncol. 2016;7:45-52. Clinical trials.gov.

61

Isatuximab: Anti-CD38 Monoclonal Antibody Safety • IRR (38%): the most-common AR specific to isatuximab • Isa-Pd common ARs: cytopenias, IRR, infections, dyspnea, GI ARs Dosing • Slower first and second infusions • Weekly for 4 weeks then every 2 weeks WEEKS 1-4

Then ongoing

WEEKLY

EVERY 2 WEEKS

(4 doses)

•

Discontinue if IRR grade  3

Isa-Kd (1-3 prior therapies)

Isa-Pd Clinical pearls

•

IRR protection: premedicate with

– – – –

• • • •

(≥ 2 prior therapies: IMiD and PI)

Dexamethasone: 40 mg oral or IV (or 20 mg for patients aged ≥ 75 years) Acetaminophen: 650 mg to 1000 mg H2 antagonists Diphenhydramine: 25 mg to 50 mg oral or IV; IV preferred for at least the first 4 infusions

Antibody interference—type and cross BEFORE starting In combo with pomalidomide + dex: DVT prophylaxis Herpes prophylaxis No dose adjustments for isatuximab

AR = adverse reaction; dex = dexamethasone; DVT = deep vein thrombosis; GI = gastrointestinal; H = histamine; IMiD = immunomodulatory imide drug; Isa = isatuximab; IRR = infusion-related reaction; Isa-RVd = isatuximab lenalidomide bortezomib dexamethasone; IV = intravenous; Kd = carfilzomib dexamethasone; Pd = pomalidomide dexamethasone; PI = proteasome inhibitor.

Wilmoth J, et al. Clin J Oncol Nurs. 2021;25(6):706-712. SARCLISA® (isatuximab) Prescribing Information. Goldschmidt H, et al. ASH 2021. Abstr #463.

62

Isatuximab: ICARIA-MM Clinical Trial •

Isatuximab improved ORR: 60.4% Isa-Pd vs 35.3% Pd ICARIA-MM Phase 3 Clinical Trial

Significant increase in median PFS demonstrated with isatuximab + Pd vs Pd alone

40% reduction in the risk of disease progression or death in patients treated with isatuximab + Pd vs Pd

Isa = isatuximab; ORR = objective response rate; Pd = pomalidomide dexamethasone; PFS = progression-free survival.

SARCLISA® (isatuximab) Prescribing Information.

63

Isatuximab Added to RVd Improves Response Rate and Depth of Response MRD Negative at End of Induction Odds Ratio: 1.83 (95% CI, 1.34-2.51) P < 0.001 60 50

Patients (%)

GMMG-HD7: phase 3 clinical trial in newly diagnosed transplant-eligible patients with MM • Isa-RVd (n = 331) vs VRd (n = 329) • Followed by ASCT, maintenance (Isa-R or R) Conclusions • Isa added to VRd produced superior rates of MRD negativity vs VRd alone • No increased rates of SAEs or discontinuations in Isa-VRd vs VRd

50.1%

40

35.6%

30 20 10 0

Isa-RVd (n = 331) WATCH FOR maintenance phase results from this ongoing trial

VRd (n = 329)

Not assessable/missinga MRD status low: Isa-VRd, 10.6%; VRd, 15.2%

ASCT = autologous stem cell transplant; Isa-R = isatuximab lenalidomide; Isa-RVd = isatuximab lenalidomide bortezomib dexamethasone; MM = multiple myeloma; MRD = minimal residual disease; R = lenalidomide; SAE = serious adverse event; VRd = bortezomib lenalidomide dexamethasone. aDue

either to loss to follow-up, missing bone marrow samples, or technical failures in measurement counted as nonresponders.

Goldschmidt H, et al. ASH 2021. Abstr #463.

64

Elotuzumab: Anti-SLAMF-7 Monoclonal Antibody • IV monoclonal antibody targeting SLAMF-7 • Prescribed with len-dex or pom-dex – DVT prophylaxis (for len or pom) – Steroid side effects and schedule (AM vs PM) • Clinical pearls – Prophylaxis for infusion reactions – Infuse at rate of 0.5 mL/min and escalate to 5 mL/min over time – Give weekly for 8 weeks then twice monthly until progressive disease – Multiple dosing regimens—check prescribing information • Monitoring – Blood counts (hold/adjust dose if needed) – Response assessment (monthly); interference – Glucose (dex can affect) – Renal and hepatic function

EPd (≥ 2 prior therapies)

dex = dexamethasone; DVT = deep vein thrombosis; EPd = elotuzumab pomalidomide dexamethasone; ERd = elotuzumab lenalidomide dexamethasone; DVT = deep vein thrombosis; H = histamine; IV = intravenous; len = lenalidomide; pom = pomalidomide; SLAMF-7 = signaling lymphocytic activation molecule 7 (also CD319, CS1).

EMPLICITI™ (elotuzumab) Prescribing Information. Gleason C, et al. J Adv Pract Oncol. 2016;7(suppl 1):53-57.

ERd (1-3 prior therapies)

65

Special Considerations With Antibody Therapy • Potential interference with laboratory tests – Co-migration of therapeutic antibody with M-protein: overestimation of M-protein and reduced CR rates

• Solutions – Awareness – Laboratory assays to minimize effects (eg, high-resolution mass spectrometry)

Daratumumab, elotuzumab, and isatuximab are all IgG antibodies CR = complete response; Ig = immunoglobulin; M-protein = monoclonal protein.

Mills JR, Murray DL. J Appl Lab Med. 2017;1(4):421-431.

66

CASE 2 Judy* *HIPAA-compliant, not actual patient name, stock photo.

PATIENT NOTES

• 60-year-old woman diagnosed with MM in 2017 – High risk: del 17p – Dara-Rd (clinical trial) – History of controlled COPD; amyloid negative

• 64 years old, symptomatic relapse August 2021:

– Cytopenias, bone marrow, platelets dropping – Light chains increasing

• Shared decision making: selinexor-Vd (BOSTON regimen) CHF, congestive heart failure; COPD = chronic obstructive pulmonary disease; Dara-Rd = daratumumab lenalidomide dexamethasone; HIPAA = Health Insurance Portability and Accountability Act; MM = multiple myeloma; Vd = bortezomib dexamethasone.

67

Selinexor: Oral Nuclear Export Inhibitor • Oral nuclear export inhibitor: blocks tumor cells from exporting tumor suppressor proteins → selective apoptosis of tumor cells

• Clinical pearls

SVd (≥ 1 prior therapy)

Sd (≥ 4 prior therapies: refractory to 2 PIs, 2 IMiDs, anti-CD38 mAb)

– Patient education – Proactive AE management is crucial • Patients must be given TWO anti-nauseants prophylactically for management of nausea and anorexia (start ondansetron day 1; adding olanzapine and/or aprepitant) • Thrombocytopenia and neutropenia (weekly blood counts in cycle 1) • Hyponatremia (salty snacks, oral hydration) • Diarrhea (oral hydration)

AE = adverse event; IMiD = immunomodulatory imide drug; mAb = monoclonal antibody; MM = multiple myeloma; PI = proteasome inhibitor; Sd = selinexor dexamethasone; SVd = selinexor bortezomib dexamethasone.

XPOVIO™ (selinexor) Prescribing Information. Mikhael J, et al. Clin Lymphoma Myeloma Leuk. 2020;20(6):351-357.

68

BOSTON Phase 3 Trial: SVd Combination Dosed Weekly •

Patients with MM with 1 to 3 lines of therapy

– 76% exposed to prior PI, 38% prior lenalidomide

•

402 patients: SVd (n = 195) vs Vd (n =207)

Conclusions • Once-weekly SVd significantly improved PFS and ORR compared to twice-weekly Vd – 76% ORR with SVd vs 62% with Vd • Rates of PN were significantly reduced – PN grade ≥ 2 was 21% with SVd vs 34% with Vd; P = 0.001 • Numerically fewer deaths on SVd vs Vd

Patients at Risk, n

HR = hazard ratio; mDOR = median duration of response; mOS = median overall survival; MM = multiple myeloma; NR = not reached; ORR = objective response rate; PI = proteasome inhibitor; PN = peripheral neuropathy; PFS = progression-free survival; SVd = selinexor bortezomib dexamethasone; Vd = bortezomib dexamethasone.

Dimopoulos MA, et al. ASCO 2020. Abstr #8501. Grosicki S, et al. Lancet. 2020;396(10262):1563-1573.

69

Selinexor: Best Practices for Optimizing Treatment White Paper—Discussion With IMF Nurse Leadership Board https://www.myeloma.org /nlb-publications

Upfront discussions with patients should be individualized and include: •

Description of the unique MOA of selinexor and the implications for clinical efficacy and toxicity profile in MM • Use key words such as “tumor suppressors” to convey the novel MOA to patients • Oral route of administration and the availability of all-oral combination regimens • Toxicity profile (including potential GI AEs) and proactive strategies for managing AEs • Requirement for potential prophylactic medications to prevent/mitigate/manage toxicities • Set expectations for potential dosing changes based on tolerability Patient support programs can help address patient-specific concerns or issues, such as insurance coverage, financial assistance, discussion of medications and/or AEs, and care coordination AE = adverse event; GI = gastrointestinal; IMF = International Myeloma Foundation; MM = multiple myeloma; MOA = mechanism of action.

IMF Nurse Leadership Board White Paper: Selinexor: Best Practices for Optimizing Treatment White Paper—Discussion With IMF Nurse Leadership Board. Accessed April 2,2022. https://www.myeloma.org/nlb-publications.

70

Articles That Have Selinexor Use Guidance: Supportive Care and Monitoring

Published June 2020 in Clinical Lymphoma, Myeloma & Leukemia

Mikhael J, et al. Clin Lymphoma Myeloma Leuk. 2020;20(6):351-357. Nooka AK, et al. Clin Lymphoma Myeloma Leuk. 2022:S2152-2650(22)00031-3.

In Press in Clinical Lymphoma, Myeloma & Leukemia 71

CASE 2 Judy* PATIENT NOTES *HIPAA-compliant, not actual patient name, stock photo.

• September 2021: 50% reduction in light chains (VGPR) • November 2021: Judy wanted to end therapy due to nausea (3 months on SVd)

– –

Discussed how she was taking selinexor (dosing at night) Recommended a change: small breakfast with ondansetron and dexamethasone, then take selinexor

UPDATE:

• Feeling much less nausea • Staying on selinexor with continued response • Enjoying spring and gardening

AE = adverse event; GI = gastrointestinal; HIPAA = Health Insurance Portability and Accountability Act; SVd = selinexor bortezomib dexamethasone; VGPR = very good partial response.

72

CASE 3 Melvin*

*HIPAA-compliant, not actual patient name, stock photo.

PATIENT NOTES

• Male, diagnosed with MM in 2010 at age 65 – Standard risk by cytogenetics • Standard risk by cytogenetics – Bortezomib/dex transplant • VRd then then transplant Treatment – Thal/dex • Kd History: IRd (clinical trial) – Ixazomib Rd• (clinical trial) • Dara/pom/dex→pom maintenance – Daratumumab/pomalidomide/dex

*HIPAA-compliant, stock photo (not actual patient).

• Biochemical • Generally good health relapse January 2021 • Shared decision-making: belantamab mafodotin • Now: old, biochemical relapse clinical study (DREAMM-7) or standard of care (76 years 77 years on – Initial concerns about eye AEs old): – Team provided more information on eye AEs – Identified ride service AE = adverse event; Dara = daratumumab; dex = dexamethasone; HIPAA = Health Insurance Portability and Accountability Act; IRd = ixazomib lenalidomide dexamethasone; Kd = carfilzomib dexamethasone; MM = multiple myeloma; pom = pomalidomide; VRd = bortezomib lenalidomide dexamethasone.

73

Belantamab Mafodotin: Antibody-Drug Conjugate Cytotoxic drug

MECHANISM Infusion

Antibody targeted to myeloma Cytotoxic drug designed to kill cell when internalized and released

Effector cell– mediated death

Antibody with cytotoxic drug “payload” Can kill myeloma cells in multiple ways • Antibody targets cytotoxic drug to myeloma cells • Antibody can recruit immune cells to kill myeloma cells

Myeloma cell

CD269 (BCMA) Multiple ways to kill myeloma cells

BCMA = B-cell maturation antigen.

Shah UA, Mailankody S. BMJ. 2020;370:m3176. Trudel S, et al. Blood Cancer J. 2019;9:37.

74

Belantamab Mafodotin: Antibody-Drug Conjugate Cont’d • Antibody-drug conjugate targeting BCMA • Clinical pearls

R/R MM with ≥ 4 prior therapies, including an anti-CD38 mAb, PI, IMiD

– Convenient dosing: 30-minute infusion Q3W – No routine premedications (if IRR, can premedicate for subsequent infusions) – Low IRRs, mostly with first infusion • 19% in first infusion, 6% in second infusion, 2% in third infusion – REMS program for ocular effects (changes in corneal epithelium) • Eye evaluation (visual acuity and slit lamp) at baseline and before each infusion – Many patients experience ocular ARs; most resolve, few discontinuations • Ocular AR in 77% of the 218 patients in the pooled safety population: keratopathy (76%), changes in visual acuity (55%), blurred vision (27%), and dry eye (19%) • Clinically significant decrease in visual acuity to 20/40 in 19%; 88% resolved, with median time to resolution of 22 days • 3% discontinuation for ocular AR – Other ARs mostly mild, grade 1 or 2 (nausea, pyrexia, fatigue, IRR) – Consider ride service such as Uber health.com AR = adverse reaction; BCMA = B-cell maturation antigen; IMiD = immunomodulary imide drug; IRR = infusion rate reaction; mAb = monoclonal antibody; PI = proteasome inhibitor; Q3W = every 3 weeks; REMS = Risk Evaluation and Mitigation Strategy; R/R = relapsed/refractory.

BLENREP (belantamab mafodotin) Prescribing Information. Lonial S, et al. ASH 2020. Abstr #1417. Lonial S, et al. Lancet Oncol. 2020:21(2):207-221. Nooka AK, et al. ASCO 2020. Abstr #8502.

75

DREAMM-2 Phase 2 Clinical Trial: Belantamab Mafodotin Design 196 patients with R/R MM (> 3 lines of therapy) • Progressive disease • Refractory to IMiDs and PIs and refractory/intolerant to anti-CD38

Results 40

Response (%)

35

.

Response Rates ORR: 34% CR: 4%

30 25

ORR: 30% sCR: 4%

VGPR: 13%

CR: 6%

20 15 10

VGPR: 10% PR: 17% PR: 10%

5

Patient-Reported Outcomes • Disease symptoms, functioning, and QoL did not worsen over time • General improvement in fatigue • EORTC-QLQ-C30 data suggest that overall HRQoL and patient functioning remained stable while on belantamab mafodotin treatment

Single-agent belantamab mafodotin at 2.5 mg/kg Q3W was well tolerated and efficacious in the treatment of patients with R/R MM, with comparable ORR, DoR, and PFS and a manageable safety profile, irrespective of the number of prior lines of therapy

0 3-6 Prior Lines of Therapy (n = 47)

≥ 7 Prior Lines of Therapy (n = 50)

CR = complete response; DoR = duration of response; EORTC-QLQ-C30 = European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire; HRQoL = health-related quality of life; IMiD = immunomodulary imide drug; MM = multiple myeloma; ORR = objective response rate; PFS = progression-free survival; PI = proteasome inhibitor; PR = partial response; Q3W = every 3 weeks; R/R = relapsed/refractory; sCR = stringent complete response; VGPR = very good partial response.

Lonial S, et al. ASH 2029. Abstr #2278. Lonial S, et al. ASH 2020. Abstr #1417. Lonial S, et al. Lancet Oncol. 2020:21(2):207-221. Nooka AK, et al. ASCO 2020. Abstr #8502.

76

Questions 1 Through 9 of OSDI Tool May Help Identify Patients With Keratopathy • Questions 1 through 9 of OSDI were •

administered to patients undergoing treatment with belantamab mafodotin OSDI results were compared with slit lamp corneal evaluation

OSDI Negative No items 1-5 “all of the time” AND no items 6-9 ≥ “most of the time”

OSDI Positive At least one item 1-5 “all of the time” OR at least one item 6-9 ≥ “most of the time”

OSDI = Ocular Surface Disease Index.

Popat R, et al. ASH 2020. Abstr #2278.

OSDI • Open access pdf available at: https://static1.squarespace.com/static/5a7915b 649fc2b945a095fa3/t/5aadf828562fa7d5c70a4b e0/1521350696433/OSDI.pdf

Grade 0-2 Keratopathy

Grade 3-4 Keratopathy

35%

6%

20%

11%

Patients who were OSDI negative had grade 3 or 4 keratopathy only 6% of the time

WATCH FOR • More data on using OSDI 77

CASE 3 Melvin* PATIENT NOTES Update • Male, diagnosed with MM in 2010 at age 65 – Standard risk by cytogenetics • Standard risk by cytogenetics – Bortezomib/dex transplant • VRd then then transplant (DIAGNOSED – Thal/dex • Kd WITH–MM IN Rd • (clinical IRd (clinical trial) Ixazomib trial) 2010): • Dara/pom/dex→pom maintenance – Daratumumab/pomalidomide/dex

*HIPAA-compliant, not actual patient name, stock photo.

*HIPAA-compliant, stock photo (not actual patient).

• Generally good health • On belantamab mafodotin, raising M-protein • Now: 77 years old, biochemical relapse

January 2022:

• Conducted FISH testing: t(11,14) • Shared-decision making: venetoclax

Dara = daratumumab; dex = dexamethasone; FISH = fluorescence in situ hybridization; HIPAA = Health Insurance Portability and Accountability Act; IRd = ixazomib lenalidomide dexamethasone; Kd = carfilzomib dexamethasone; MM = multiple myeloma; pom = pomalidomide; VRd = bortezomib lenalidomide dexamethasone.

79

BELLINI Phase 3 Clinical Trial: Vd ± Venetoclax Design

Conclusions:

• 291 patients with MM, 1 to 3 prior therapies • Patients treated with Vd ± Ven

•

Results for t(11;14) subset (per investigator, with median follow-up: 22.7 months) Vd + Ven

Vd

HR (95% CI)

Median PFS t(11;14)

NR

9.3 mo

0.095 (0.020-0.458)

OS

NR

NR

0.649 (0.129-3.253)

ORR

95%

47%

Not reported

MRD < 10-5

25%

0%

Not reported

• Common AEs (all grades): diarrhea, nausea, constipation, fatigue • Grade 3 AEs: hematologic events, pneumonia, diarrhea • Increased infections, risk of death with venetoclax

•

Updated analysis continues to reflect a favorable benefit-risk profile for Vd + Ven in patients with t(11;14) – Clinically meaningful PFS improvement – Trend toward OS improvement Higher ORR and deeper responses with Vd + Ven

Vd + Ven is a good regimen for patients with t(11;14) but not appropriate for other patients with MM

AE = adverse event; HR = hazard ratio; MM = multiple myeloma; MRD = minimal residual disease; NR = not reached; ORR = objective response rate; OS = overall survival; PFS = progressionfree survival; Vd = bortezomib dexamethasone; Ven = venetoclax.

Moreau P, et al. ASH 2019. Abstr #1888. Kumar S, et al. ASCO 2020. Abstr #8509.

80

Venetoclax Clinical Pearls • Venetoclax is a BCL-2 inhibitor currently FDA approved for CLL and AML (off label for MM)

• Deep responses in patients with MM, but increased infections, including serious infections, death

• Particular efficacy in patients with MM with t(11;14) or high expression of BCL2

• AEs associated with venetoclax in other indications (eg, TLS) may not be similar to AEs in patients with MM

• Expanded access program provides free drug if insurance

WATCH FOR

New clinical data on venetoclax in patients with MM

denies coverage to patients with MM

• Clinical trials are available AE = adverse event; AML = acute myeloid leukemia; BCL-2 and BCL2 = B-cell lymphoma 2; CLL = chronic lymphocytic leukemia; FDA = US Food and Drug Administration; MM = multiple myeloma; TLS = tumor lysis syndrome.

VENCLEXTA® (venetoclax) Prescribing Information. Kumar S, et al. ASCO 2020. Abstr #8509. Kumar SK, et al. Lancet Oncology. 2020;21(12):1630-1642. Basali D, et al. Br J Haematol. 2020;189(6):1136-1140. Faiman B, Gleason C clinical experience.

81

Summary Although some patients are exceptional responders, most patients with MM relapse, with clones evolving over time and becoming resistant to therapy The relapse workup for MM includes laboratory blood work (CBC, chemistry) and imaging for bone involvement

There are many options for treating patients with relapsed MM; considerations include prior therapies, response to prior therapies, research results, clinician experience, and patient preference Anticoagulation is important for patients receiving myeloma therapies, including IMiDs, doxorubicin, or carfilzomib regimens

Selinexor is a novel nuclear export inhibitor now approved for patients with ≥ 1 prior therapy, in combination with Vd

Belantamab mafodotin is an antibody-drug conjugate with efficacy in heavily pretreated MM; unique ocular AEs (keratopathy)

Venetoclax is a BCL-2 inhibitor that is an appropriate treatment for patients with MM containing t(11,14); deep responses with increased risk of infection

AE = adverse event; BCL-2 = B-cell lymphoma 2; CBC, complete blood count; IMiD = immunomodulatory imide drug; MM = multiple myeloma; Vd = bortezomib dexamethasone.

Paquin A, et al. Blood Cancer J. 2020;10(8):87. Keats JJ, et al. Blood. 2012;120(5):1067-1076. Hillengass J, et al. Lancet Oncol. 2019;20(6):e302-e312. Ghobrial IM, et al. Blood. 2014;124:3380-3388.

Rajkumar SV, et al. Lancet Oncol. 2014;15:e538-3548. Faiman B, et al. J Adv Pract Oncol. 2016;2016:7(suppl 1):17-29. NCCN Guidelines®. Multiple Myeloma. V5.2022. Accessed March 15, 2022. Moreau P, et al. Lancet Oncol. 2021;22(3):e105-e118. Sanfilippo KM, et al. Am J Hematol. 2019;94(11):1176-1184. XPOVIO™ (selinexor) Prescribing Information. Grosicki S, et al. Lancet. 2020;396(10262):1563-1573.

Mikhael J, et al. Clin Lymphoma Myeloma Leuk. 2020;20(6):351-357. Nooka AK, et al. Clin Lymphoma Myeloma Leuk. 2022:S2152-2650(22)00031-3. BLENREP (belantamab mafodotin) Prescribing Information.

Lonial S, et al. Lancet Oncol. 2020:21(2):207-221. VENCLEXTA® (venetoclax) Prescribing Information. Kumar S, et al. ASCO 2020. Abstr #8509. Kumar SK, et al. Lancet Oncol. 2020;21(12):1630-1642.

82

International Myeloma Foundation 800-452-CURE (2873) http://myeloma.org

Emerging Therapies in MM, Including CAR T-Cell Therapies and Bispecific Antibodies CASE 4: Maria*

CASE 5: Carlos* *HIPAA-compliant; not actual patient names.

Donna Catamero, ANP-BC, OCN, CCRC Beth Faiman, PhD, RN, MSN, APRN-BC, AOCN, BMTCN, FAAN

CAR = chimeric antigen receptor; HIPAA = Health Insurance Portability and Accountability Act.

BCMA Is a Target for Multiple Myeloma Therapy BCMA (B-Cell Maturation Antigen) • Member of TNF receptor superfamily • BCMA is expressed on late memory B cells committed to PC differentiation and PCs • BCMA plays a role in survival of longlived PCs • BCMA is expressed more abundantly on malignant PCs than on normal ones

BCMA = B-cell maturation antigen; MM = multiple myeloma; PC = plasma cell; TNF = tumor necrosis factor.

Shah N, et al. Leukemia. 2020;34(4):985-1005. Yu B, et al. J Hematol Oncol. 2020;13:125.

BCMA

MM cell

84

Mechanism of Action for Novel BCMA-Targeted Therapies CAR T CELLS

BISPECIFIC ANTIBODIES Viral vector

T cell

T cell

Cytotoxic cytokines

Cytotoxic cytokines

MM cell

scFv BCMA CD3 MM cell

BCMA

Bispecific antibody

MM cell death

MM cell death

BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; MM = multiple myeloma; scFV = single chain fragment variable.

Shah N, et al. Leukemia. 2020;34(4):985-1005. Yu B, et al. J Hematol Oncol. 2020;13:125.

85

CASE 4 Maria* *HIPAA-compliant, not actual patient name, stock photo.

PATIENT NOTES 67-year-old woman diagnosed with IgA lambda MM, standard risk in 2009

TREATMENT:

MARCH 2021:

• • • • •

Rd then ASCT with CR—declined maintenance Bortezomib + dex—VGPR Elo + pom + dex—VGPR Carfilzomib + dex—CR Daratumumab + bortezomib + dex—VGPR

Idecabtagene vicleucel approved—patient interested in therapy

ASCT = autologous stem cell transplant; CR = complete response; dex = dexamethasone; Elo = elotuzumab; HIPAA = Health Insurance Portability and Accountability Act; Ig = immunoglobulin; MM = multiple myeloma; pom = pomalidomide; Rd = lenalidomide dexamethasone; VGPR = very good partial response.

86

CAR T-Cell Therapy: A New Treatment Approach Patient consenting and education

Patient selection

Patient screening

Patient screening

Apheresis

Apheresis

Bridging and lymphodepletion

Bridging and lymphodepletion

Infusion and inpatient monitoring

Infusion and inpatient monitoring

Post-discharge monitoring

Post-discharge monitoring

Pre-infusion

CAR = chimeric antigen receptor.

Teoh PJ, Chng WJ. Blood Cancer J. 2021;11(4):84. Shah UA, Mailankody S. BMJ. 2020;370:m3176. Catamero D, et al. J Adv Pract Oncol [in press].

87

Idecabtagene Vicleucel KarMMa Phase 2 Clinical Trial Design

• •

Idecabtagene vicleucel (ide-cel; bb2121): CAR T-cell therapy targeting BCMA 128 patients with R/R MM treated in dose-escalation study – ≥ 3 prior therapies, including PI, IMiD, and anti-CD38 OR refractory to last regimen – Median of 6 prior therapies

R/R MM after ≥ 4 lines of therapy (including a PI, an IMiD, and an anti-CD38 mAb) March 2021

Response at 450 × 106 CAR T cells 100

ORR = 82% (N = 55)

Results for 450 × 106 CAR T-cell dose

Patients (%)

80

35% CR/sCR 60 40 20

47% PR

• • •

82% ORR (35% CR/sCR) Median DoR: 11.3 months 96% CRS, with 6% grade ≥ 3

Data cutoff: October 16, 2019

0

Ide-cel BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; CR = complete response; CRS = cytokine release syndrome; DoR = duration of response; IMiD = immunomodulatory imide drug; mAb = monoclonal antibody; MM = multiple myeloma; ORR = objective response rate; PI = proteasome inhibitor; PR = partial response; R/R = relapsed/refractory; sCR = stringent complete response.

ABECMA® (idecabtagene vicleucel) Prescribing Information. Munshi NC, et al. ASCO 2020. Abstr #8503. Munshi NC, et al. N Engl J Med. 2021;384:705-716.

89

Ciltacabtagene Autoleucel R/R MM after ≥ 4 lines of therapy

CARTITUDE-1 Phase 1b/2 Clinical Trial Design

• •

CAR T-cell therapy with 2 BCMA-targeting domains 97 patients with progressive MM – ≥ 3 prior therapies, including PI, IMiD, and anti-CD38 OR refractory to PI and IMiD – Median of 6 prior therapies

Results

• • •

94.8% ORR Deep responses: of 52 evaluable for MRD, 94.2% were MRD negative at 10-5 Median time to first response: 1 month (range, 0.9-5.8 mo; 80.4% ≤ 1.0 mo) Median PFS, DoR, OS not reached 10 deaths on study (8 due to AEs related and unrelated, 2 PD)

Data cutoff: May 20, 2020

ORR = 94.8% 100

February 2022

(N = 97)

80

Patients (%)

• •

(including a PI, an IMiD, and an anti-CD38 mAb)

60

55.7% sCR

40 20 0

32.0% VGPR 7.2% PR

Cilta-cel

AE = adverse event; BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; DoR = duration of response; IMiD = immunomodulatory imide drug; mAb = monoclonal antibody; MM = multiple myeloma; MRD = minimal residual disease; OS = overall survival; ORR = objective response rate; PD = progressive disease; PFS = progression-free survival; PI = proteasome inhibitor; PR = partial response; R/R = relapsed/refractory; sCR = stringent complete response; VGPR = very good partial response.

CARVYKTI™ (ciltacabtagene autoleucel) Prescribing Information. Madduri D, et al. ASH 2020. Abstr #177. Berdja JG, et al. ASCO 2020. Abstr #8505. Madduri D, et al. ASH 2019. Abstr #577.

90

CAR T-Cell Therapies: Immediate and Long-Term Considerations FREQUENT AEs (>20%)

CRS, infections, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, nausea, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite Neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia

SELECT AEs TO ASSESS

CRS Neurotoxicity (ICANS) Hypogammaglobulinemia Prolonged and recurrent cytopenias

RECOMMENDED MONITORING

Patients should be monitored at least daily for 7 to 10a days after CAR T-cell infusion at certified health care facility to monitor for CRS and neurotoxicity Patients should stay close to certified health care facility for ≥4 weeks after infusion and should not drive or participate in hazardous activities for ≥8 weeks after infusion Monitor blood count and immunoglobulin levels after infusion; use growth factor support and/or transfusion for cytopenia and administer IVIG for IgG < 400 mg/dL

PROPHYLAXIS

Antiviral prophylaxis

CAR = chimeric antigen receptor; CRS = cytokine release syndrome; ICANS = immune effector cell–associated neurotoxicity syndrome; Ig, immunoglobulin; IVIG = intravenous immunoglobulin. aRecommended

monitoring at certified facility for idecabtagene vicleucel, 7 days and for ciltacabtagene autoleucel, 10 days.

ABECMA™ (idecabtagene vicleucel) Prescribing Information. Usmani S, et al. ASCO 2021. Abstr #8005. CARVYKTI™ (ciltacabtagene autoleucel) Prescribing Information. Shah UA, Mailankody S. BMJ. 2020;370:m3176.

91

CRS Severity Ranges From Mild to Life-Threatening: Early Recognition and Treatment RESPIRATORY

HEPATIC

RENAL

HEMATOLOGIC

CONSTITUTIONAL

Hypoxia Dyspnea Capillary leak syndrome Transaminitis  ALP Hyperbilirubinemia  Serum creatinine Renal insufficiency TLS

Anemia Thrombocytopenia Neutropenia

Fever Fatigue, malaise Headache

NEUROLOGIC

CARDIOVASCULAR

GASTROINTESTINAL

MUSCULOSKELETAL

Delirium Somnolence Dysphagia

Sinus tachycardia Hypotension Arrhythmias

Nausea Vomiting Diarrhea  CPK Myalgia Weakness

Monitoring for CRS • Vital signs (temperature, •

O2 saturation, etc) Review of systems and physical exam

–

Focus on cardiovascular, pulmonary, and neurologic systems

• Rule out infection • Laboratory monitoring – – – –

CRP Cytokines Ferritin LDH

ALP = alkaline phosphatase; CPK = creatine phosphokinase; CRP = C-reactive protein; CRS = cytokine release syndrome; LDH = lactate dehydrogenase; O2 = oxygen; TLS = tumor lysis syndrome.

Oluwole OO, Davila ML. J Leukoc Biol. 2016;100:1265-1272. June CH, et al. Science. 2018;359:1361-1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45-55. Shimabukuro-Vornhagen, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.

92

Managing CRS Grade

1

Tocilizumab Tocilizumab: Onset ≥72 hr after infusion, treat symptomatically; onset <72 hr after infusion, consider tocilizumab 8 mg/kg IV over 1 hr Corticosteroids: Consider dexamethasone 10 mg IV every 24 hr

Tocilizumab: 8 mg/kg IV over 1 hr, repeat every 8 hr as needed if not responsive to IV fluids or supplemental O2 Corticosteroids: Dexamethasone 10 mg IV every 12-24 hr

2-3

If no improvement in 24 hr or rapid progression, repeat tocilizumab and escalate to dexamethasone 20 mg IV every 6-12 hr If no improvement in 24 hr or continued rapid progression, repeat tocilizumab and switch to methylprednisolone 2 mg/kg followed by 2 mg/kg divided 4 times/day

4 (ICU/ critical care required)

•

Tocilizumab: 8 mg/kg IV over 1 hr, repeat every 8 hr as needed if not responsive to IV fluids or supplemental O2 Corticosteroids: Dexamethasone 20 mg IV every 6 hr If no improvement in 24 hr consider methylprednisolone (1-2 g, repeat every 24 hr if needed; taper as clinically indicated) or other anti–T-cell therapies

After 2 doses of tocilizumab, consider alternative anticytokine agents; do not exceed 3 doses of tocilizumab in 24 hr, or 4 doses total

CRS = cytokine release syndrome; ICU = intensive care unit; IV = intravenous; O2 = oxygen.

ABECMA™ (idecabtagene vicleucel) Prescribing Information. CARVYKTI™ (ciltacabtagene autoleucel) Prescribing Information.

93

Neurotoxicity Rare but Potentially Serious AE Hallucinations

Ataxia

Altered wakefulness

Apraxia

Monitoring for Neurotoxicity (ICANS) • ICE tool • Review of systems and physical exam

– Facial nerve palsy

Confusion

Headache

Neurotoxicity

• •

• Encephalopathy

Seizures

Rule out infection If ICANS suspected

– –

Tremors

•

Focus on neurologic systems

Neuroimaging (ideally MRI) Diagnostic lumbar puncture for opening pressure and infection tests

Corticosteroids are typically indicated for ICANS ≥ grade 2 Patient and caregiver information

CRS = cytokine release syndrome; ICANS = immune effector cell–associated neurotoxicity syndrome; ICE = Immune Effector Cell Encephalopathy screening tool; MRI = magnetic resonance imaging.

Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.

94

ICE Screening Tool for Neurological Assessment Assessment Orientation Naming

Points

Orientation to year, month, city, hospital

Scoring

4

Ability to name 3 objects (eg, point to clock, pen, button)

3

Following commands

Ability to follow simple commands (eg, “Show me 2 fingers” or “Close your eyes and stick out your tongue”)

1

Writing

Ability to write a standard sentence (eg, “Our national bird is the bald eagle”)

1

Attention

Ability to count backwards from 100 by 10

1

10

No impairment

7-9

Grade`1 ICANS

3-6

Grade 2 ICANS

0-2

Grade 3 ICANS

0 due to patient unarousable and unable to perform ICE assessment

Grade 4 ICANS

Total Points ICANS = immune effector cell–associated neurotoxicity syndrome; ICE = Immune Effector Cell Encephalopathy screening tool.

Santomasso B, et al. Am Soc Clin Oncol Educ Book. 2019;39:433-444. Lee DW, et al. Biol Blood Marrow Transplant. 2018;15:47-62.

95

CASE 4 Mary Maria* *HIPAA-compliant, not actual patient name, stock photo.

PATIENT NOTES PATIENT NOTES 67-year-old female diagnosed with IgA lambda MM, •standard June 2021: risk Financial in 2016 and medical consult at CAR T-cell center • October 2021: symptomatic relapse • VTD-PACE (X1) • Rd then ASCT (no maintenance)–CR • Bortezomib + dex–VGPR • November: received slot for CAR T-cell therapy generation • Elo + pom + dex–VGPR TREATMENT • December: T-cell • harvest Carfilzomib + dex–CR • VTD-PACE bridging therapy • Daratumumab + bortezomib + dex–VGPR • January: CAR T-cell therapy infusion Approved—patient interested in therapy • Mild 2021 CRS (gradeIde1),Celcytopenias MARCH • CR

CAR = chimeric antigen receptor; CR = complete response; CRS = cytokine release syndrome; HIPAA = Health Insurance Portability and Accountability Act; VTD-PACE = bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide.

96

Post–CAR T-Cell Therapy Patient Education • Infection prevention – –

Prophylaxis What to do if there are signs of infection

• Symptoms of neurotoxicity to watch for

• Patient handout to give to ER or other medical professionals

• Ongoing monitoring • Transfusion possibility

CAR = chimeric antigen receptor; ER = emergency room.

Catemero D, et al. Jadpro in press. ABECMA™ (idecabtagene vicleucel) Prescribing Information. Usmani S, et al. ASCO 2021. Abstr #8005. CARVYKTI™ (ciltacabtagene autoleucel) Prescribing Information.

Shah UA, Mailankody S. BMJ. 2020;370:m3176. Catamero D, et al. J Adv Pract Oncol [in press].

97

Clinical Trials: Early Access to Promising Treatments Preclinical

PHASE 1

PHASE 2

PHASE 3

PHASE 4

ANIMAL STUDIES FIRST INTRODUCTION OF AN INVESTIGATIONAL DRUG INTO HUMANS

• • •

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

EVALUATION OF EFFECTIVENESS IN A CERTAIN TUMOR TYPE

• •

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

GATHER ADDITIONAL EFFECTIVENESS AND SAFETY INFORMATION COMPARED TO STANDARD OF CARE

• •

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

APPROVED AGENTS IN NEW POPULATIONS OR NEW DOSE FORMS

AE = adverse event; DLT = dose-limiting toxicity; MTD = maximum tolerated dose; PD = pharmacodynamics; PK = pharmacokinetics.

Faiman B, et al. Adv Pract Oncol. 2016;7:17-29.

98

How to Find Clinical Trials

Clinicaltrials.gov https://clinicaltrials.gov/

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

99

Clinical Trial Myths: Importance of Dispelling Inaccuracies MYTH: If I participate in a clinical trial, I might get a placebo, not active treatment

MYTH: If I participate in a clinical trial, I can’t change my mind

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

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

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

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

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

MYTH: Clinical trials are expensive and not covered by insurance

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

MM = multiple myeloma.

PhRMA website. Accessed April 15, 2022. https://phrma.org/-/media/Project/PhRMA/PhRMA-Org/PhRMA-Org/PDF/A-C/CLINICAL-TRIALS-MYTH-FACT-PRINT.pdf?hsCtaTracking=f6689b95-1626-40d98c87-c6b8d31600a4%7C35221aa8-d487-4db3-9416-b9c3c35e3bac.

100

Importance of Participation by Diverse Populations in Clinical Trials “[P]eople from racial and ethnic minority and other diverse groups are underrepresented in clinical research. This is a concern because people of different ages, races, and ethnicities may react differently to certain medical products.” –FDA US Cancer Centers of Excellence Strategies for Increased Inclusion of Racial and Ethnic Minorities in Clinical Trials Leadership and commitment

Investigator hiring, training, and mentoring practices

Community engagement practices

Patient engagement practices

• • • • •

Cultural competency training Community advisory boards Lay community representatives (ambassadors) Transparency in sharing research findings Working with patient organizations

• Engaging the patient in trial participation decision-making • Ensuring the availability of culturally appropriate, ethnicity-specific, and cognitively empowering materials • Earning the trust of the patient

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

101

CASE 5 *HIPAA-compliant, not actual patient name, stock photo.

Carlos* Abraham •PATIENT Male, standard-risk MM diagnosed 2013 at age 64 NOTES TREATMENT HISTORY

• Male, diagnosed with MM in 2009 at age 65 • cytogenetics SMM monitored – Standard risk by • then Standard risk by cytogenetics – Bortezomib/dex transplant DIAGNOSED: • RVD then transplant + R maintenance – Thal/dex SMM IN 2010 • Carfilzomib/pomalidomide/dex – Ixazomib Rd (clinical trial) MM IN 2013 • Elotuzumab/lenalidomide/dex – Daratumumab/pomalidomide/dex • Daratumumab/pomalidomide/dex • Generally good health • Now: 77 years old,•biochemical relapse Biochemical relapse February 2021 (72 years old): • Discussed clinical trial participation

dex = dexamethasone; HIPAA = Health Insurance Portability and Accountability Act; MM = multiple myeloma; R = lenalidomide; RVD = lenalidomide bortezomib dexamethasone; SMM = smoldering multiple myeloma.

102

Therapies in Development for Treatment of Multiple Myeloma CAR T-cell therapies • P-BCMA-101 (BCMA) • PHE885 (BCMA) • ALLO-715 (BCMA)

CAR NK cell

CAR T cell

Monoclonal antibodies • TAK-079 (CD38) • Felzartamab (CD38)

CAR NK cells

TCR MHC

T cell

Checkpoint inhibitors • Nivolumab (PD-1) • Pembrolizumab (PD-1)

PD-1

Antibody-drug conjugates • Lorvotuzumab mertansine (CD56) • Indatuximab ravtansine (CD138)

PD-L1

Plasma cell T cell

CELMoD agents • Iberdomide (cereblon E3 ligase) • CC-92480 (cereblon E3 ligase)

WATCH FOR • New data • New drug approvals in MM

Immune cells T cell

Bispecific antibodies/ T-cell engagers • AMG 701 (BCMA) • CC-93269 (BCMA) • Teclistamab (BCMA) • REGN545B (BCMA) • Elranatamab (BCMA) • Talquetamab (GPRC5D)

BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; CELMoD = cereblon E3 ligase modulator; MHC = major histocompatibility complex; MM = multiple myeloma; NK = natural killer; PD-1 = programmed death protein 1; PD-L1 = programmed death ligand 1; TCR = T-cell receptor.

Shah UA, Mailankody S. BMJ. 2020;370:m3176. Yang et al. J Hematol Oncol. 2020;13:150. Bruins WSC, et al. Front Immunol. 2020;11:1155. Matyskiela ME, et al. J Med Chem. 2018;61:535-542.

Richardson, et al. ASCO 2020. Abstr #8500. Mailankody S. ASH 2020. Abstr #129. Van De Donk NWCJ, et al. ASH 2020. Abstr #724. Gershman J. Pharmacy Times. Accessed April 10, 2022. https://www.pharmacytimes.com/view/a-look-at-multiple-myeloma-treatment-options-in-the-pipeline.

103

MajesTEC-1: Phase 1/2 Study of Teclistamab, a BCMATargeting Bispecific Antibody Study Design • Patients with R/R MM with median of 5 prior lines of therapy all received teclistamab – 100% triple-class exposed; 77% triple-class refractory – 69% penta-drug exposed, 29% penta-drug refractory Results • ORR: 65% (95% CI, 48-79) • ≥ VGPR rate: 60% (95% CI, 43-75) • CR or better rate: 40% (95% CI, 25-57) • Median DoR has not been reached; the 6-month DoR rate is 90% (95% CI, 63-97)

BCMA = B-cell maturation antigen; DoR = duration of response; MM = multiple myeloma; R/R = relapsed/refractory.

Moreau P, et al. ASH 2021. Abstr #896.

104

MonumenTAL-1: Phase 1 Study of Talquetamab, a GPRC5D Bispecific Antibody Duration of Response

Study Design • Patients with R/R MM all received talquetamab – 100% triple-class exposed; 77% triple-class refractory – 80% penta-drug exposed, 20% penta-drug refractory – 17% prior BCMA-directed therapy Two doses: 405 µg/kg weekly and 800 µg/kg biweekly • No treatment discontinuations due to AEs • Most common AEs: CRS, neutropenia, dysgeusia, dry mouth, skin/nail disorders, and infection • 405 µg/kg weekly: ORR 70% (≥ VGPR rate: 57%) • 800 µg/kg every other week: ORR 71% (≥ VGPR rate: 53%) AE = adverse event; BCMA = B-cell maturation antigen; CRS = cytokine release syndrome; GPRC5D = G-protein coupled receptor family C group 5 member D; MM = multiple myeloma; R/R = relapsed/refractory; ORR = objective response rate.

Krishnan AY, et al. ASH 2021. Abstr #158.

105

CASE 5 *HIPAA-compliant, not actual patient name, stock photo.

Carlos* Abraham NOTES •PATIENT Male, standard-risk MM diagnosed 2013 • Male, diagnosed TREATMENT HISTORYwith MM in 2009 at age 65

– Standard risk by cytogenetics – Bortezomib/dex then transplant • Entered MajesTEC-1: phase 1 study of – Thal/dex teclistamab March 2021 – Ixazomib Rd (clinical trial)dosing to 1500 µg/kg weekly • Step-up (72 years old): – Daratumumab/pomalidomide/dex • CRS, neutropenia • Generally good health • CR • Now: 77 years old, biochemical relapse

CR = complete response; CRS = cytokine release syndrome; HIPAA = Health Insurance Portability and Accountability Act; MM = multiple myeloma.

106

Summary BCMA is a protein found on the surface of mature B cells and is a target for myeloma treatments

Bispecific antibodies such as teclistamab and talquetamab are being studied in clinical trials in patients with MM

Clinical trials can give patients early access to promising therapies, but misconceptions and disparities exist

CRS is a common AE with both CAR T-cell therapy and bispecific antibodies that can be managed with tocilizumab and corticosteroids

CAR T-cell therapy engineers a patient’s own T cells; early referral to CAR T-cell therapy center for evaluation and preauthorization is important for access

Many new drugs are in development for MM, including monoclonal antibodies, bispecific antibodies (T-cell engagers), antibody-drug conjugates, and CELMoD agents

AE = adverse event; BCMA = B-cell maturation antigen; CAR = chimeric antigen receptor; CELMoD = cereblon E3 ligase modulator; CRS = cytokine release syndrome; MM = multiple myeloma.

Shah N, et al. Leukemia. 2020;34(4):985-1005. Yu B, et al. J Hematol Oncol. 2020;13:125. Faiman B, et al. Adv Pract Oncol. 2016;7:17-29. PhRMA website. Accessed April 15, 2022. https://phrma.org/-/media/Project/PhRMA/PhRMA-Org/PhRMAOrg/PDF/A-C/CLINICAL-TRIALS-MYTH-FACT-PRINT.pdf?hsCtaTracking=f6689b95-1626-40d9-8c87-c6b8d31600a4%7C35221aa8-d487-4db3-9416-b9c3c35e3bac. Cho S-F, et al. Front Immunol. 2018;10;9:1821. Teoh PJ, Chng WJ. Blood Cancer J. 2021;11(4):84. Shah UA, Mailankody S. BMJ. 2020;370:m3176. Catamero D, et al. J Adv Pract Oncol [in press]. Oluwole OO, Davila ML. J Leukoc Biol. 2016;100:1265-1272. June CH, et al. Science. 2018;359:1361-1365. Brudno JN, Kochenderfer JN. Blood. 2016;127(26):3321-3330. Brudno JN, Kochenderfer JN. Blood Rev. 2019:34:45-55. Shimabukuro-Vornhagen A, et al. J Immunother Cancer. 2018;6:56. Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638.. ang Y, et al. J Hematol Oncol.

2020;13:150. Bruins WSC, et al. Front Immunol. 2020;11:1155. Matyskiela ME, et al. J Med Chem. 2018;61:535-542. Richardson, et al. ASCO 2020. Abstr #8500. Van De Donk NWCJ, et al. ASH 2020.

107 Abstr #724. ASH 2021 Gershman J. Pharmacy Times. Accessed April 10, 2022. https://www.pharmacytimes.com/view/a-look-at-multiple-myeloma-treatment-options-in-the-pipeline.

Thank You for Sharing in the Stories of Our Patients Melvin*

Anthony* Judy*

Carlos* Maria* *HIPAA-compliant, not actual patient name, stock photo.

108

We Hope You Had an Enjoyable and Educational Time As a result of this program, you learned to:

Discuss treatment regimens for patients with newly diagnosed or relapsed multiple myeloma (MM), including appropriate symptom management and patient education

Identify health care disparities faced by patients with MM who are members of minority groups and strategies to overcome these disparities

Describe strategies to support the patient’s input in therapeutic decisions

109

And Have Gained Resources to Enhance Your Ability to Care for Your Patients With MM http://imf-ons.myeloma.org/resources password: ons2022 OR

MM = multiple myeloma.

110

Thank You for Your Attendance and Participation On behalf of the International Myeloma Foundation with the generous support from AbbVie, Inc.; Amgen; Bristol Myers Squibb Company; GlaxoSmithKline; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; Karyopharm Therapeutics; and Takeda Pharmaceuticals U.S.A., Inc., we thank you.

Please Contact IMF for Further Information and Resources: 1-800-452-CURE TheIMF@myeloma.org (1-800-452-2873) http://myeloma.org Slides at: www.imf-ons.myeloma.org/ONS_2022.pdf Resources at: http://imf-ons.myeloma.org/resources password: ons2022

CE = continuing education; IMF = International Myeloma Foundation.

EVALUATION & CE CREDIT

Place in box at exit or hand to staff 111